ELANE

Summary

Gene Symbol: ELANE
Description: elastase, neutrophil expressed
Alias: ELA2, HLE, HNE, PMN-E, SCN1, neutrophil elastase, PMN elastase, bone marrow serine protease, elastase 2, neutrophil, elastase-2, granulocyte-derived elastase, leukocyte elastase, medullasin, polymorphonuclear elastase
Species: human
Products:     ELANE

Top Publications

  1. Pratt C, Tobin R, Church F. Interaction of heparin cofactor II with neutrophil elastase and cathepsin G. J Biol Chem. 1990;265:6092-7 pubmed
    We investigated the interaction of the human plasma proteinase inhibitor heparin cofactor II (HC) with human neutrophil elastase and cathepsin G in order to examine 1) proteinase inhibition by HC, 2) inactivation of HC, and 3) the effect ..
  2. Sera Y, Kawaguchi H, Nakamura K, Sato T, Habara M, Okada S, et al. A comparison of the defective granulopoiesis in childhood cyclic neutropenia and in severe congenital neutropenia. Haematologica. 2005;90:1032-41 pubmed
    ..Mutations in the neutrophil elastase gene, ELA2, have been reported in patients with CyN and in those with SCN...
  3. Korkmaz B, Hajjar E, Kalupov T, Reuter N, Brillard Bourdet M, Moreau T, et al. Influence of charge distribution at the active site surface on the substrate specificity of human neutrophil protease 3 and elastase. A kinetic and molecular modeling analysis. J Biol Chem. 2007;282:1989-97 pubmed
    The biological functions of human neutrophil protease 3 (Pr3) differ from those of neutrophil elastase despite their close structural and functional resemblance...
  4. Bellanne Chantelot C, Clauin S, Leblanc T, Cassinat B, Rodrigues Lima F, Beaufils S, et al. Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register. Blood. 2004;103:4119-25 pubmed
    Heterozygous mutations of the gene encoding neutrophil elastase (ELA2) have been associated with cyclic neutropenia (CN) and severe congenital neutropenia (SCN)...
  5. Papayannopoulos V, Metzler K, Hakkim A, Zychlinsky A. Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J Cell Biol. 2010;191:677-91 pubmed publisher
    ..We show that upon activation, neutrophil elastase (NE) escapes from azurophilic granules and translocates to the nucleus, where it partially degrades ..
  6. Skokowa J, Fobiwe J, Dan L, Thakur B, Welte K. Neutrophil elastase is severely down-regulated in severe congenital neutropenia independent of ELA2 or HAX1 mutations but dependent on LEF-1. Blood. 2009;114:3044-51 pubmed publisher
    ..present study we demonstrated that ELA2 mRNA expression in myeloid progenitors and plasma protein levels of neutrophil elastase (NE) were markedly reduced in patients with CN harboring mutations in either ELA2 or HAX-1 genes...
  7. Matsumoto T, Wada H, Nobori T, Nakatani K, Onishi K, Nishikawa M, et al. Elevated plasma levels of fibrin degradation products by granulocyte-derived elastase in patients with disseminated intravascular coagulation. Clin Appl Thromb Hemost. 2005;11:391-400 pubmed
    ..These results suggest that GE-XDP is a potentially useful marker for the diagnosis of overt-DIC and as a predictor of organ failure-related outcome. ..
  8. Köllner I, Sodeik B, Schreek S, Heyn H, von Neuhoff N, Germeshausen M, et al. Mutations in neutrophil elastase causing congenital neutropenia lead to cytoplasmic protein accumulation and induction of the unfolded protein response. Blood. 2006;108:493-500 pubmed
    ..Heterozygous mutations in the gene encoding neutrophil elastase (ELA2) have been reported in both diseases...
  9. Ancliff P, Gale R, Liesner R, Hann I, Linch D. Mutations in the ELA2 gene encoding neutrophil elastase are present in most patients with sporadic severe congenital neutropenia but only in some patients with the familial form of the disease. Blood. 2001;98:2645-50 pubmed
    ..Heterozygous mutations in the ELA2 gene encoding neutrophil elastase were detected in all families studied...

More Information

Publications98

  1. Klein C, Grudzien M, Appaswamy G, Germeshausen M, Sandrock I, Schäffer A, et al. HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). Nat Genet. 2007;39:86-92 pubmed
    ..Our findings suggest that HAX1 is a major regulator of myeloid homeostasis and underline the significance of genetic control of apoptosis in neutrophil development. ..
  2. Salipante S, Benson K, Luty J, Hadavi V, Kariminejad R, Kariminejad M, et al. Double de novo mutations of ELA2 in cyclic and severe congenital neutropenia. Hum Mutat. 2007;28:874-81 pubmed
    Heterozygous mutations of ELA2, encoding the protease neutrophil elastase (NE), cause either autosomal dominant cyclic neutropenia or severe congenital neutropenia (SCN)...
  3. Takahashi H, Nukiwa T, Basset P, Crystal R. Myelomonocytic cell lineage expression of the neutrophil elastase gene. J Biol Chem. 1988;263:2543-7 pubmed
    Human neutrophil elastase (NE) functions as a powerful serine protease capable of attacking a broad range of proteins. To examine the cellular site(s) of NE gene expression, a 0...
  4. Fouret P, du Bois R, Bernaudin J, Takahashi H, Ferrans V, Crystal R. Expression of the neutrophil elastase gene during human bone marrow cell differentiation. J Exp Med. 1989;169:833-45 pubmed
    b>Neutrophil elastase, a potent serine protease carried and released by activated neutrophils, is not synthesized by neutrophils, but by their bone marrow precursor cells...
  5. Chan S, Leung V, Ip M, Shum D. Shed syndecan-1 restricts neutrophil elastase from alpha1-antitrypsin in neutrophilic airway inflammation. Am J Respir Cell Mol Biol. 2009;41:620-8 pubmed publisher
    Persistent proteolytic imbalance in chronic inflammatory diseases has been ascribed to neutrophil elastase (NE)/antielastase imbalance in wound fluids...
  6. Grenda D, Murakami M, Ghatak J, Xia J, Boxer L, Dale D, et al. Mutations of the ELA2 gene found in patients with severe congenital neutropenia induce the unfolded protein response and cellular apoptosis. Blood. 2007;110:4179-87 pubmed
    ..Mutations of the ELA2 gene encoding neutrophil elastase (NE) are responsible for most cases of SCN and cyclic neutropenia (CN), a related but milder disorder of ..
  7. Shiohara M, Shigemura T, Saito S, Tanaka M, Yanagisawa R, Sakashita K, et al. Ela2 mutations and clinical manifestations in familial congenital neutropenia. J Pediatr Hematol Oncol. 2009;31:319-24 pubmed publisher
    ..neutropenia (SCN) and cyclic neutropenia (CN) in addition to 3 sporadic cases of SCN were analyzed for neutrophil elastase (Ela2) gene mutation...
  8. Rosenberg P, Alter B, Link D, Stein S, Rodger E, Bolyard A, et al. Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia. Br J Haematol. 2008;140:210-3 pubmed
    ..Registry who were on long-term treatment with granulocyte colony-stimulating factor and for whom the neutrophil elastase (ELA2) gene was sequenced...
  9. Wang Z, Chen F, Zhai R, Zhang L, Su L, Lin X, et al. Plasma neutrophil elastase and elafin imbalance is associated with acute respiratory distress syndrome (ARDS) development. PLoS ONE. 2009;4:e4380 pubmed publisher
    ..an exploratory study of genome-wide gene expression in whole blood and found that the expression of neutrophil elastase inhibitor (PI3, elafin) was down-regulated during the early phase of ARDS...
  10. Newburger P, Pindyck T, Zhu Z, Bolyard A, Aprikyan A, Dale D, et al. Cyclic neutropenia and severe congenital neutropenia in patients with a shared ELANE mutation and paternal haplotype: evidence for phenotype determination by modifying genes. Pediatr Blood Cancer. 2010;55:314-7 pubmed publisher
    ..Mutations of the ELANE gene (the symbol recently replacing ELA2) are considered largely responsible for most cases of CN and SCN, but ..
  11. Person R, Li F, Duan Z, Benson K, Wechsler J, Papadaki H, et al. Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2. Nat Genet. 2003;34:308-12 pubmed
    ..as a candidate for association with neutropenia in affected individuals without mutations in ELA2 (encoding neutrophil elastase), the most common cause of severe congenital neutropenia (SCN; ref. 3)...
  12. Germeshausen M, Deerberg S, Peter Y, Reimer C, Kratz C, Ballmaier M. The spectrum of ELANE mutations and their implications in severe congenital and cyclic neutropenia. Hum Mutat. 2013;34:905-14 pubmed publisher
    b>Neutrophil elastase gene (ELANE) mutations are responsible for the majority of cases of severe congenital neutropenia (CN) and cyclic neutropenia (CyN)...
  13. Reeves E, Lu H, Jacobs H, Messina C, Bolsover S, Gabella G, et al. Killing activity of neutrophils is mediated through activation of proteases by K+ flux. Nature. 2002;416:291-7 pubmed
    ..We show that it is the proteases, thus activated, that are primarily responsible for the destruction of the bacteria. ..
  14. Dale D, Person R, Bolyard A, Aprikyan A, Bos C, Bonilla M, et al. Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia. Blood. 2000;96:2317-22 pubmed
    ..3, and this disease is now attributable to mutations of the gene encoding neutrophil elastase (the ELA2 gene)...
  15. Horwitz M, Benson K, Person R, Aprikyan A, Dale D. Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis. Nat Genet. 1999;23:433-6 pubmed
    ..3. We identified 7 different single-base substitutions in the gene (ELA2) encoding neutrophil elastase (EC 3. 4.21...
  16. Kainulainen V, Wang H, Schick C, Bernfield M. Syndecans, heparan sulfate proteoglycans, maintain the proteolytic balance of acute wound fluids. J Biol Chem. 1998;273:11563-9 pubmed
    ..Thus, syndecans are shed into acute wound fluids, where they can modify the proteolytic balance of the fluid. This suggests a novel physiological role for these soluble heparan sulfate proteoglycans. ..
  17. Farley D, Salvesen G, Travis J. Molecular cloning of human neutrophil elastase. Biol Chem Hoppe Seyler. 1988;369 Suppl:3-7 pubmed
    The human U937 cell line, a promonocyte-like leukemic line, has been shown to synthesize neutrophil elastase (Senior, R. M. et al. (1982) J. Clin. Invest. 69, 384-393)...
  18. Xia J, Bolyard A, Rodger E, Stein S, Aprikyan A, Dale D, et al. Prevalence of mutations in ELANE, GFI1, HAX1, SBDS, WAS and G6PC3 in patients with severe congenital neutropenia. Br J Haematol. 2009;147:535-42 pubmed publisher
    Severe congenital neutropenia (SCN) is a genetically heterogeneous syndrome associated with mutations of ELANE (ELA2), HAX1, GFI1, WAS, CSF3R or G6PC3...
  19. Jackson P, Xu X, Wilson L, Weathington N, Clancy J, Blalock J, et al. Human neutrophil elastase-mediated cleavage sites of MMP-9 and TIMP-1: implications to cystic fibrosis proteolytic dysfunction. Mol Med. 2010;16:159-66 pubmed publisher
    ..We demonstrated increased gelatinolytic activity in CF sputum. These samples had elevated human neutrophil elastase (HNE) levels which correlated with an increased MMP-9/TIMP-1 ratio...
  20. Ancliff P, Gale R, Watts M, Liesner R, Hann I, Strobel S, et al. Paternal mosaicism proves the pathogenic nature of mutations in neutrophil elastase in severe congenital neutropenia. Blood. 2002;100:707-9 pubmed
    Heterozygous mutations in neutrophil elastase have been detected in many sporadic cases of congenital neutropenia...
  21. Veinberg G, Potorocina I, Vorona M. Recent trends in the design, synthesis and biological exploration of ?-lactams. Curr Med Chem. 2014;21:393-416 pubmed
    ..with anti-inflammatory, antiviral, anticancer and other activities based on the inhibition of human leukocyte elastase, porcine pancreatic elastase, tryptase, chymase, human cytomegalovirus protease, fatty acid amide hydrolase, ..
  22. Soria J, Acera A, Duran J, Boto de los Bueis A, Del Hierro Zarzuelo A, Gonzalez N, et al. The analysis of human conjunctival epithelium proteome in ocular surface diseases using impression cytology and 2D-DIGE. Exp Eye Res. 2018;167:31-43 pubmed publisher
    ..in the pathological groups (Annexin-A1, α-enolase, Annexin-A2, S100A8, cytokeratin-1, Peroxiredoxin-2 and Leukocyte elastase inhibitor) and downregulation of 2 proteins (Galectin-3 and Lipocalin-1)...
  23. Kim T, Gu J, Jung H, Koh Y, Kim I, Kim H. Elevated extracellular trap formation and contact system activation in acute leukemia. J Thromb Thrombolysis. 2018;46:379-385 pubmed publisher
    ..and XII), D-dimer, thrombin generation, extracellular trap markers (histone-DNA complex, cell-free dsDNA, leukocyte elastase), and contact system markers (activated factor XII [XIIa], high-molecular-weight kininogen, prekallikrein, ..
  24. Maffia P, Zittermann S, Scimone M, Tateosian N, Amiano N, Guerrieri D, et al. Neutrophil elastase converts human immature dendritic cells into transforming growth factor-beta1-secreting cells and reduces allostimulatory ability. Am J Pathol. 2007;171:928-37 pubmed
    ..confirmed by examining PMN CS from two patients with cyclic neutropenia, a disease due to mutations in the neutrophil elastase gene...
  25. Bellanti F, Romano A, Lo Buglio A, Castriotta V, Guglielmi G, Greco A, et al. Oxidative stress is increased in sarcopenia and associated with cardiovascular disease risk in sarcopenic obesity. Maturitas. 2018;109:6-12 pubmed publisher
    ..reduced glutathione (GSH), oxidized glutathione (GSSG), plasma malondialdehyde-(MDA) and 4-hydroxy-2,3-nonenal-(HNE) protein adducts were analyzed...
  26. Lim C, Han J. The antioxidant xanthorrhizol prevents amyloid-?-induced oxidative modification and inactivation of neprilysin. Biosci Rep. 2018;38: pubmed publisher
    ..Accumulation of A? generates reactive oxygen species (ROS) such as 4-hydroxynonenal (HNE), and then reduces activities of A?-degrading enzymes including NEP...
  27. Wiesmeier M, Gautam S, Kirschnek S, Hacker G. Characterisation of Neutropenia-Associated Neutrophil Elastase Mutations in a Murine Differentiation Model In Vitro and In Vivo. PLoS ONE. 2016;11:e0168055 pubmed publisher
    ..Several underlying gene defects have been identified in SCN patients. Mutations in the neutrophil elastase (ELANE) gene are frequently found in SCN and cyclic neutropenia...
  28. Lin H, Liu S, Yen E, Li T, Lai I. microRNA-183 Mediates Protective Postconditioning of the Liver by Repressing Apaf-1. Antioxid Redox Signal. 2017;26:583-597 pubmed publisher
    ..Moreover, iPoC and agomiR-183 decreased the expression of Apaf-1 and 4-HNE after IR injury in mouse livers, whereas the antagomiR-mediated prevention of miR-183 expression led to increased ..
  29. Zhu J, Nathan C, Jin W, Sim D, Ashcroft G, Wahl S, et al. Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Cell. 2002;111:867-78 pubmed
    Increased leukocyte elastase activity in mice lacking secretory leukocyte protease inhibitor (SLPI) leads to impaired wound healing due to enhanced activity of TGFbeta and perhaps additional mechanisms...
  30. Jaworek J, Szklarczyk J, Bonior J, Kot M, Goralska M, Pierzchalski P, et al. Melatonin metabolite, N(1)-acetyl-N(1)-formyl-5-methoxykynuramine (AFMK), attenuates acute pancreatitis in the rat: in vivo and in vitro studies. J Physiol Pharmacol. 2016;67:411-21 pubmed
    ..Lipid peroxidation products (MDA + 4-HNE) and the activity of an antioxidant enzyme glutathione peroxidase (GPx) were measured in pancreatic tissue...
  31. Noh G, Han J, Cheong C, Han Y, Kim N. Novel anal sphincter saving procedure with partial excision of levator-ani muscle in rectal cancer invading ipsilateral pelvic floor. Ann Surg Treat Res. 2017;93:195-202 pubmed publisher
    ..This hemilevator excision (HLE) technique enables preserving the anal sphincter function while obtaining oncologic clearance and avoiding ..
  32. Gai Z, Gui T, Hiller C, Kullak Ublick G. Farnesoid X Receptor Protects against Kidney Injury in Uninephrectomized Obese Mice. J Biol Chem. 2016;291:2397-411 pubmed publisher
    ..The effects were accentuated by uninephrectomy. In human renal biopsies, staining of 4-hydroxynonenal (4-HNE), glucose-regulated protein 78 (Grp78), and C/EBP-homologous protein, markers of endoplasmic reticulum stress, was ..
  33. Yamaguchi R, Sakamoto A, Yamamoto T, Narahara S, Sugiuchi H, Yamaguchi Y. Differential regulation of IL-23 production in M1 macrophages by TIR8/SIGIRR through TLR4- or TLR7/8-mediated signaling. Cytokine. 2017;99:310-315 pubmed publisher
    ..IL-12p40 production by M1 macrophages pretreated with human neutrophil elastase (HNE) was synergistically enhanced IL-12p40, but not IL-23 production, after exposure to lipopolysaccharide ..
  34. Zhang B, Dong J, Chen Y, Liu Y, Huang S, Zhong X, et al. Nrf2 mediates the protective effects of homocysteine by increasing the levels of GSH content in HepG2 cells. Mol Med Rep. 2017;16:597-602 pubmed publisher
    ..Furthermore, 4‑hydroxynonenal (4‑HNE)‑induced cell injury was attenuated by Hcy; however, this protective effect was blocked by the GSH‑..
  35. Cabrera Muñoz A, Rojas L, Alonso Del Rivero Antigua M, Pires J. 1H, 13C and 15N resonance assignments and secondary structure analysis of CmPI-II, a serine protease inhibitor isolated from marine snail Cenchritis muricatus. Biomol NMR Assign. 2016;10:153-6 pubmed publisher
    ..CmPI-II is a tight-binding inhibitor of serine proteases: trypsin, human neutrophil elastase (HNE), subtilisin A and pancreatic elastase...
  36. Teppner M, Böss F, Ernst B, Pähler A. Application of lipid peroxidation products as biomarkers for flutamide-induced oxidative stress in vitro. Toxicol Lett. 2015;238:53-9 pubmed publisher
    ..This study shows the potential of different lipid peroxidation products, namely isoprostanes and hydroxynonenal (HNE) derivatives, to serve as early safety biomarkers of hepatotoxicity caused by oxidative stress as underlying ..
  37. Qiu Y, Zhang Y, Hu N, Dong F. A Truncated Granulocyte Colony-stimulating Factor Receptor (G-CSFR) Inhibits Apoptosis Induced by Neutrophil Elastase G185R Mutant: IMPLICATION FOR UNDERSTANDING CSF3R GENE MUTATIONS IN SEVERE CONGENITAL NEUTROPENIA. J Biol Chem. 2017;292:3496-3505 pubmed publisher
    Mutations in ELANE encoding neutrophil elastase (NE) have been identified in the majority of patients with severe congenital neutropenia (SCN)...
  38. Levesque J, Takamatsu Y, Nilsson S, Haylock D, Simmons P. Vascular cell adhesion molecule-1 (CD106) is cleaved by neutrophil proteases in the bone marrow following hematopoietic progenitor cell mobilization by granulocyte colony-stimulating factor. Blood. 2001;98:1289-97 pubmed
    ..Two serine proteases, namely, neutrophil elastase and cathepsin G, were identified, which cleave VCAM-1 and are released by neutrophils accumulating in the ..
  39. Hajjar E, Broemstrup T, Kantari C, Witko Sarsat V, Reuter N. Structures of human proteinase 3 and neutrophil elastase--so similar yet so different. FEBS J. 2010;277:2238-54 pubmed publisher
    Proteinase 3 and neutrophil elastase are serine proteinases of the polymorphonuclear neutrophils, which are considered to have both similar localization and ligand specificity because of their high sequence similarity...
  40. Kraehenbuehl K, Pagé Zoerkler N, Mauroux O, Gartenmann K, Blank I, Bel Rhlid R. Selective enzymatic hydrolysis of chlorogenic acid lactones in a model system and in a coffee extract. Application to reduction of coffee bitterness. Food Chem. 2017;218:9-14 pubmed publisher
    ..Hog liver esterase (HLE) hydrolyzed chlorogenic acid lactones (CQALs, FQALs) selectively, while chlorogenate esterase hydrolyzed all ..
  41. Grann V, Ziv E, Joseph C, Neugut A, Wei Y, Jacobson J, et al. Duffy (Fy), DARC, and neutropenia among women from the United States, Europe and the Caribbean. Br J Haematol. 2008;143:288-93 pubmed publisher
    ..model that included percentage African ancestry, national origin, cytokines, socio-economic factors and the ELA2 rs57834246 SNP, only the DARC rs2814778 genotype and C-reactive protein were associated with ANC (P < 0.0001)...
  42. Önder C, Kurgan Å, Altıngöz S, Bağış N, Uyanık M, Serdar M, et al. Impact of non-surgical periodontal therapy on saliva and serum levels of markers of oxidative stress. Clin Oral Investig. 2017;21:1961-1969 pubmed publisher
    ..Malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and 4-hydroxy-2-nonenal (4-HNE) were assessed in saliva and serum samples before and after the non-surgical treatment by enzyme-linked immune ..
  43. Macedo A, Moraes L, Mizobuti D, Fogaça A, Moraes F, Hermes T, et al. Low-Level Laser Therapy (LLLT) in Dystrophin-Deficient Muscle Cells: Effects on Regeneration Capacity, Inflammation Response and Oxidative Stress. PLoS ONE. 2015;10:e0128567 pubmed publisher
    ..The mdx group showed significant increase in H2O2 production and 4-HNE levels compared to the Ctrl group and LLLT treatment reduced this increase...
  44. Grunwald E, Tatiyaborworntham N, Faustman C, Richards M. Effect of 4-hydroxy-2-nonenal on myoglobin-mediated lipid oxidation when varying histidine content and hemin affinity. Food Chem. 2017;227:289-297 pubmed publisher
    The compound 4-hydroxy-2-nonenal (HNE) dissolved in water was examined to remove potential effects of using ethanol to solubilize the aldehyde such as altering protein structure or redox properties of myoglobin (Mb)...
  45. Aoki Y, Hase T. The primary structure and elastinolytic activity of medullasin (a serine protease of bone marrow). Biochem Biophys Res Commun. 1991;178:501-6 pubmed
    The amino acid sequence around the carboxyl terminal of medullasin was determined by digesting the protease with carboxypeptidase Y and measuring the rate of release of amino acids from the carboxyl terminal...
  46. Lin L, Betsuyaku T, Heimbach L, Li N, Rubenstein D, Shapiro S, et al. Neutrophil elastase cleaves the murine hemidesmosomal protein BP180/type XVII collagen and generates degradation products that modulate experimental bullous pemphigoid. Matrix Biol. 2012;31:38-44 pubmed publisher
    ..Mice lacking neutrophil elastase (NE) do not develop experimental BP...
  47. Noro T, Namekata K, Azuchi Y, Kimura A, Guo X, Harada C, et al. Spermidine Ameliorates Neurodegeneration in a Mouse Model of Normal Tension Glaucoma. Invest Ophthalmol Vis Sci. 2015;56:5012-9 pubmed publisher
    ..were carried out at 8 and 12 weeks old, and immunoblot and immunohistochemical analyses of 4-hydroxy-2-nonenal (4-HNE) in the retina were performed at 8 weeks old...
  48. Shearn C, Smathers R, Backos D, Reigan P, Orlicky D, Petersen D. Increased carbonylation of the lipid phosphatase PTEN contributes to Akt2 activation in a murine model of early alcohol-induced steatosis. Free Radic Biol Med. 2013;65:680-692 pubmed publisher
    The production of reactive aldehydes such as 4-hydroxynonenal (4-HNE) is a key event in the pathogenesis of alcoholic liver disease (ALD), which ranges from simple steatosis to fibrosis...
  49. Velez J, Miriyala S, Nithipongvanitch R, Noel T, Plabplueng C, Oberley T, et al. p53 Regulates oxidative stress-mediated retrograde signaling: a novel mechanism for chemotherapy-induced cardiac injury. PLoS ONE. 2011;6:e18005 pubmed publisher
    ..4HNE in WT mice but not p53((-/-)) mice receiving DOX treatment, as determined by co-immunoprecipitation of HNE and pJNK...
  50. Hill R, Singh I, Wang J, Hall E. Time courses of post-injury mitochondrial oxidative damage and respiratory dysfunction and neuronal cytoskeletal degradation in a rat model of focal traumatic brain injury. Neurochem Int. 2017;111:45-56 pubmed publisher
    ..The LP also results in the formation of neurotoxic reactive aldehyde byproducts including 4-hydroxynonenal (4-HNE) and propenal (acrolein) which exacerbates ROS/RNS production and oxidative protein damage in the injured brain...
  51. Shao M, Nadel J. Neutrophil elastase induces MUC5AC mucin production in human airway epithelial cells via a cascade involving protein kinase C, reactive oxygen species, and TNF-alpha-converting enzyme. J Immunol. 2005;175:4009-16 pubmed
    ..Human neutrophil elastase (HNE) exists in high concentrations (1-20 microM) in airway secretions of these patients and induces ..
  52. Li Y, Zheng G, Liu Y. [Salubrinal protects human lens epithelial cells against endoplasmic reticulum stress-associated apoptosis]. Zhonghua Yan Ke Za Zhi. 2016;52:437-43 pubmed publisher
    ..Hydrogen peroxide (H2O2 200 ?mol/L) was used to intervene in the cultured human lens epithelial cells B3 (HLE-B3) so as to create an oxidative stress model and induce ERS in the model...
  53. Wang S, Clarke P, Davis R, Mumuni S, Kwabi Addo B. Sex steroid-induced DNA methylation changes and inflammation response in prostate cancer. Cytokine. 2016;86:110-118 pubmed publisher
    ..included CXCL12, CXCL5, CCL25, IL1F8, IL13RAI, STAT5A, CXCR4 and TLR5; and genes that were hypermethylated included ELA2, TOLLIP, LAG3, CD276 and MALT1...
  54. Jiang S, Teague A, Tryggestad J, Chernausek S. Role of microRNA-130b in placental PGC-1?/TFAM mitochondrial biogenesis pathway. Biochem Biophys Res Commun. 2017;487:607-612 pubmed publisher
    ..In addition, miR-130b-3p anti-sense inhibitor increased TFAM expression and reduced 4-hydroxynonenal (4-HNE)-induced production of reactive oxygen species (ROS)...
  55. Rani B, Malfettone A, Dituri F, Soukupová J, Lupo L, Mancarella S, et al. Galunisertib suppresses the staminal phenotype in hepatocellular carcinoma by modulating CD44 expression. Cell Death Dis. 2018;9:373 pubmed publisher
    ..Galunisertib modulated the expression of stemness-related genes only in the invasive (HLE and HLF) HCC cells inducing a decreased expression of CD44 and THY1...
  56. Zhou H, Zeng C, Yang T, Long F, Kuang X, Du J. Lentivirus-mediated klotho up-regulation improves aging-related memory deficits and oxidative stress in senescence-accelerated mouse prone-8 mice. Life Sci. 2018;200:56-62 pubmed publisher
    ..This treatment reduced memory deficits, neuronal loss, synaptic damage and 4-HNE levels but increased mitochondrial manganese-superoxide dismutase (Mn-SOD) and catalase (CAT) expression...
  57. Citron B, Ameenuddin S, Uchida K, Suo W, Santacruz K, Festoff B. Membrane lipid peroxidation in neurodegeneration: Role of thrombin and proteinase-activated receptor-1. Brain Res. 2016;1643:10-7 pubmed publisher
    ..first time that thrombin dose-dependently induces formation of HNEPA in NSC34 mouse motor neuron cells using anti-HNE and anti-acrolein monoclonal antibodies. The most prominent immunoreactive band, in SDS-PAGE, was at ?54kDa...
  58. O Hare Doig R, Chiha W, Giacci M, Yates N, Bartlett C, Smith N, et al. Specific ion channels contribute to key elements of pathology during secondary degeneration following neurotrauma. BMC Neurosci. 2017;18:62 pubmed publisher
    ..Similarly, HNE immunoreactivity and loss of oligodendrocyte precursor cells were only limited by treatment with all three ion ..
  59. Huang Y, Wang P, Huang L, Lai C, Yang W, Wu K, et al. Prenatal Nonylphenol and Bisphenol A Exposures and Inflammation Are Determinants of Oxidative/Nitrative Stress: A Taiwanese Cohort Study. Environ Sci Technol. 2017;51:6422-6429 pubmed publisher
    ..peroxidation (8-iso-prostaglandin F2? (8-isoPF2?) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA))...
  60. Lu Y, Lin M, Aitken R. Exposure of spermatozoa to dibutyl phthalate induces abnormal embryonic development in a marine invertebrate Galeolaria caespitosa (Polychaeta: Serpulidae). Aquat Toxicol. 2017;191:189-200 pubmed publisher
    ..cells experienced oxidative stress as indicated by the presence of lipid aldehydes, such as 4-hydroxynonenal (4-HNE) in the sperm acrosome and neck...
  61. Chow B, Ho C, Wong S, Waye M, Zheng M. Home environmental influences on children's language and reading skills in a genetically sensitive design: Are socioeconomic status and home literacy environment environmental mediators and moderators?. Scand J Psychol. 2017;58:519-529 pubmed publisher
    This twin study examined how family socioeconomic status (SES) and home literacy environment (HLE) contributes to Chinese language and reading skills. It included 312 Chinese twin pairs aged 3 to 11...
  62. Peacock Chambers E, Martin J, Necastro K, Cabral H, BAIR MERRITT M. The Influence of Parental Self-Efficacy and Perceived Control on the Home Learning Environment of Young Children. Acad Pediatr. 2017;17:176-183 pubmed publisher
    ..and perceived control, and 2) determine how self-efficacy and control relate to the home learning environment (HLE), including whether they mediate the relationship between sociodemographic characteristics and HLE, among low-..
  63. Allen C, Kumar A, Qutob S, Nyiri B, Chauhan V, Murugkar S. Raman micro-spectroscopy analysis of human lens epithelial cells exposed to a low-dose-range of ionizing radiation. Phys Med Biol. 2017;: pubmed publisher
    ..01 Gy to 5 Gy, on human lens epithelial (HLE) cells which were chemically fixed 24 hrs post-irradiation...
  64. Park J, He F, Martin L, Li Y, Chorley B, Adler K. Human neutrophil elastase induces hypersecretion of mucin from well-differentiated human bronchial epithelial cells in vitro via a protein kinase C{delta}-mediated mechanism. Am J Pathol. 2005;167:651-61 pubmed
    ..Mechanisms of human neutrophil elastase (HNE)-induced mucin secretion by well-differentiated normal human bronchial epithelial (NHBE) cells ..
  65. Ho S, Lee K, Chan Y, Kuo L, Ito K, Adcock I, et al. Neutrophil elastase represses IL-8/CXCL8 synthesis in human airway smooth muscle cells through induction of NF-kappa B repressing factor. J Immunol. 2009;183:411-20 pubmed publisher
    ..Hence, we describe a novel negative regulatory mechanism of NE-induced NRF, which is restricted to hASM and mediates the suppression of IL-8/CXCL8 expression. ..
  66. Reus Pons M, Kibele E, Janssen F. Differences in healthy life expectancy between older migrants and non-migrants in three European countries over time. Int J Public Health. 2017;62:531-540 pubmed publisher
    We analysed differences in healthy life expectancy at age 50 (HLE50) between migrants and non-migrants in Belgium , the Netherlands, and England and Wales, and their trends over time between 2001 and 2011 in the latter two ..
  67. Wang Y, Xiao Y, Zhong L, Ye D, Zhang J, Tu Y, et al. Increased neutrophil elastase and proteinase 3 and augmented NETosis are closely associated with ?-cell autoimmunity in patients with type 1 diabetes. Diabetes. 2014;63:4239-48 pubmed publisher
    ..Here we show that circulating protein levels and enzymatic activities of neutrophil elastase (NE) and proteinase 3 (PR3), both of which are neutrophil serine proteases stored in neutrophil primary ..
  68. Devaney J, Greene C, Taggart C, Carroll T, O Neill S, McElvaney N. Neutrophil elastase up-regulates interleukin-8 via toll-like receptor 4. FEBS Lett. 2003;544:129-32 pubmed
    Cystic fibrosis is characterised in the lungs by high levels of neutrophil elastase (NE). NE induces interleukin-8 (IL-8) expression via an IL-1 receptor-associated kinase signalling pathway...
  69. Goldmann B, Rudolph V, Rudolph T, Holle A, Hillebrandt M, Meinertz T, et al. Neutrophil activation precedes myocardial injury in patients with acute myocardial infarction. Free Radic Biol Med. 2009;47:79-83 pubmed publisher
    ..High levels of MPO plasma levels at the time of admission and the rapid peak of free plasma MPO levels after the onset of symptoms suggests that PMN activation is an early event in AMI and potentially precedes myocardial injury. ..
  70. Luo Q, Zhang Z, Liu D, Feng K, Jin X, Zhang J. Human neutrophil elastase induces MUC5AC overexpression in chronic rhinosinusitis through tumour necrosis factor-α converting enzyme. Acta Otolaryngol. 2016;136:641-8 pubmed publisher
    Conclusion The HNE-TACE signalling pathway has an important role in the process of MUC5AC overexpression in chronic rhinosinusitis (CRS). Objectives To provide evidence of HNE-induced MUC5AC overexpression in CRS via TACE...
  71. Lane A, Ley T. Neutrophil elastase cleaves PML-RARalpha and is important for the development of acute promyelocytic leukemia in mice. Cell. 2003;115:305-18 pubmed
    ..by a neutral serine protease in a human myeloid cell line; purification revealed that the protease is neutrophil elastase (NE)...
  72. Al Hussaini H, Kilarkaje N. Trans-resveratrol mitigates type 1 diabetes-induced oxidative DNA damage and accumulation of advanced glycation end products in glomeruli and tubules of rat kidneys. Toxicol Appl Pharmacol. 2018;339:97-109 pubmed publisher
    ..DNA damage, and apoptosis, and ii) localization of fibrotic changes, AGE, RAGE, 8-oxo-dG and 4-hydroxynonenal (4-HNE) in diabetic rat kidneys...
  73. Liu T, Wu X, Wang Y, Hou X, Jiang G, Wu T, et al. CD-PLLD co-delivering docetaxel and MMP-9 siRNA plasmid for nasopharyngeal carcinoma therapy in vivo. Mol Med Rep. 2017;16:1383-1388 pubmed publisher
    ..matrix metalloproteinase 9 (MMP?9) small interfering RNA, via CD?PLLD/DOC/MMP?9 complexes, into mice implanted with HNE?1 human nasopharyngeal carcinoma (NPC) tumor cells in vivo...
  74. Eggert Kruse W, Zimmermann K, Geissler W, Ehrmann A, Boit R, Strowitzki T. Clinical relevance of polymorphonuclear (PMN-) elastase determination in semen and serum during infertility investigation. Int J Androl. 2009;32:317-29 pubmed publisher
    ..However, the clinical value of routine determination of seminal plasma (SP) PMN elastase in asymptomatic patients during infertility investigation has not clearly been established and not much is ..
  75. Ramachandran R, Mihara K, Chung H, Renaux B, Lau C, Muruve D, et al. Neutrophil elastase acts as a biased agonist for proteinase-activated receptor-2 (PAR2). J Biol Chem. 2011;286:24638-48 pubmed publisher
    ..We found that none of neutrophil elastase, cathepsin-G, and proteinase-3 can activate G(q)-coupled PAR(2) calcium signaling; but all of these ..
  76. Taniguchi K, Yang P, Jett J, Bass E, Meyer R, Wang Y, et al. Polymorphisms in the promoter region of the neutrophil elastase gene are associated with lung cancer development. Clin Cancer Res. 2002;8:1115-20 pubmed
    b>Neutrophil elastase (NE) is a powerful serine protease capable of degrading most protein components of the extracellular matrix...
  77. Dellostritto D, Sinharoy P, Connell P, Fahmy J, Cappelli H, Thodeti C, et al. 4-Hydroxynonenal dependent alteration of TRPV1-mediated coronary microvascular signaling. Free Radic Biol Med. 2016;101:10-19 pubmed publisher
    ..This environment has been shown to increase lipid peroxidation byproducts including 4-Hydroxynonenal (4-HNE)...
  78. Heestermans M, Cunha M, Reitsma P, Zeerleder S, Middeldorp S, van Vlijmen B. Circulating nucleosomes and elastase ?1-antitrypsin complexes and the novel thrombosis susceptibility locus SLC44A2. Thromb Res. 2016;142:8-10 pubmed publisher
  79. Fischer B, Domowicz D, Zheng S, Carter J, McElvaney N, Taggart C, et al. Neutrophil elastase increases airway epithelial nonheme iron levels. Clin Transl Sci. 2009;2:333-9 pubmed publisher
    Alpha-1-antitrypsin (A1AT) deficiency is characterized by increased neutrophil elastase (NE) activity and oxidative stress in the lung. We hypothesized that NE exposure generates reactive oxygen species by increasing lung non-heme iron...
  80. Wiegand C, Schönfelder U, Abel M, Ruth P, Kaatz M, Hipler U. Protease and pro-inflammatory cytokine concentrations are elevated in chronic compared to acute wounds and can be modulated by collagen type I in vitro. Arch Dermatol Res. 2010;302:419-28 pubmed publisher
    ..Levels of proteases such as PMN elastase, matrix metalloproteinases-2 (MMP-2), and MMP-13 were found to be profoundly elevated in chronic when compared ..
  81. Yang B, Ni X, Chen L, Zhang H, Ren P, Feng Y, et al. Honokiol-loaded polymeric nanoparticles: an active targeting drug delivery system for the treatment of nasopharyngeal carcinoma. Drug Deliv. 2017;24:660-669 pubmed publisher
    ..drug delivery system for a sustained and targeted delivery of honokiol (HK) to the nasopharyngeal carcinoma (NPC) HNE-1 cell lines, since the folate receptor (FR) is over-expressed on their surface...
  82. El Ouriaghli F, Sloand E, Mainwaring L, Fujiwara H, Keyvanfar K, Melenhorst J, et al. Clonal dominance of chronic myelogenous leukemia is associated with diminished sensitivity to the antiproliferative effects of neutrophil elastase. Blood. 2003;102:3786-92 pubmed
    ..Patients with CML have high levels of neutrophil elastase, which has recently been shown to antagonize the action of granulocyte-colony-stimulating factor (G-CSF) ..
  83. Tang J, Li B, Liu C, Li Y, Li Q, Wang L, et al. Mechanism of Mechanical Trauma-Induced Extracellular Matrix Remodeling of Fibroblasts in Association with Nrf2/ARE Signaling Suppression Mediating TGF-?1/Smad3 Signaling Inhibition. Oxid Med Cell Longev. 2017;2017:8524353 pubmed publisher
    ..levels of TGF?1, p-Smad3, Nrf2, GPx1, and CAT were downregulated, the production of ROS, 8-OHdG, 4-HNE, and MDA was increased, and the nuclear translocation of Smad2/3 was suppressed after 5333 ?strain's ..
  84. Bai Y, Wang H, Zhao Q. Detection of human neutrophil elastase by aptamer affinity capillary electrophoresis coupled with laser-induced fluorescence using specified site fluorescently labeled aptamer. Anal Bioanal Chem. 2017;409:6843-6849 pubmed publisher
    As a multifunctional serine protease, human neutrophil elastase (HNE) plays critical roles in a variety of physiopathological processes, such as acute lung injury, emphysema, atherosclerosis, and arthritis...
  85. Zeng T, Zhang C, Zhao N, Guan M, Xiao M, Yang R, et al. Impairment of Akt activity by CYP2E1 mediated oxidative stress is involved in chronic ethanol-induced fatty liver. Redox Biol. 2018;14:295-304 pubmed publisher
    ..Ethanol exposure resulted in increased levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE)-Akt adducts, which was significantly inhibited by chlormethiazole (CMZ), an efficient CYP2E1 inhibitor...
  86. Eggers C, Murray I, Delmar V, Day A, Craik C. The periplasmic serine protease inhibitor ecotin protects bacteria against neutrophil elastase. Biochem J. 2004;379:107-18 pubmed
    ..Phylogenetic analysis suggested that ecotin has an exogenous target, possibly neutrophil elastase. Recombinant protein was expressed and purified from E...
  87. Zhou J, Perelman J, Kolosov V, Zhou X. Neutrophil elastase induces MUC5AC secretion via protease-activated receptor 2. Mol Cell Biochem. 2013;377:75-85 pubmed publisher
    ..Previous studies have demonstrated that neutrophil elastase (NE) stimulates the secretion of MUC5AC from airway epithelial cells, however, the mechanism is poorly ..
  88. Hernández González J, García Fernández R, Valiente P. Polar Desolvation and Position 226 of Pancreatic and Neutrophil Elastases Are Crucial to their Affinity for the Kunitz-Type Inhibitors ShPI-1 and ShPI-1/K13L. PLoS ONE. 2015;10:e0137787 pubmed publisher
    The Kunitz-type protease inhibitor ShPI-1 inhibits human neutrophil elastase (HNE, Ki = 2...
  89. Nustede R, Klimiankou M, Klimenkova O, Kuznetsova I, Zeidler C, Welte K, et al. ELANE mutant-specific activation of different UPR pathways in congenital neutropenia. Br J Haematol. 2016;172:219-27 pubmed publisher
    ..response (UPR) in patients with severe congenital neutropenia (CN) harbouring mutations of ELANE, encoding neutrophil elastase. Why UPR is not activated in patients with cyclic neutropenia (CyN) carrying the same ELANE mutations is ..