caspase 12


Gene Symbol: caspase 12
Description: caspase 12
Alias: caspase-12, CASP-12
Species: rat
Products:     caspase 12

Top Publications

  1. Sima A, Li Z. The effect of C-peptide on cognitive dysfunction and hippocampal apoptosis in type 1 diabetic rats. Diabetes. 2005;54:1497-505 pubmed
    ..Although these abnormalities were not fully prevented by C-peptide replacement, the findings suggest that this regime will substantially prevent cognitive decline in the type 1 diabetic population...
  2. Kumar S, Kasseckert S, Kostin S, Abdallah Y, Schafer C, Kaminski A, et al. Ischemic acidosis causes apoptosis in coronary endothelial cells through activation of caspase-12. Cardiovasc Res. 2007;73:172-80 pubmed
    ..The main pathway of the simulated ischemia-induced apoptosis consists of the Ca2+ leak from the ER followed by activation of caspase-12 and caspase-3. ..
  3. Harding H, Zhang Y, Bertolotti A, Zeng H, Ron D. Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol Cell. 2000;5:897-904 pubmed
    ..PERK thus plays a major role in the ability of cells to adapt to ER stress. ..
  4. Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner B, et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature. 2000;403:98-103 pubmed
    ..Thus, caspase-12 mediates an ER-specific apoptosis pathway and may contribute to amyloid-beta neurotoxicity. ..
  5. Florian B, Vintilescu R, Balseanu A, Buga A, Grisk O, Walker L, et al. Long-term hypothermia reduces infarct volume in aged rats after focal ischemia. Neurosci Lett. 2008;438:180-5 pubmed publisher
    ..At the transcription level, hypothermia caused a reduction in the mRNA coding for caspase 12, NF-kappa B and grp78 in the peri-infarcted region, suggesting an overall decrease in the transcriptional ..
  6. Liu L, Liu C, Lu Y, Liu L, Jiang Y. ER stress related factor ATF6 and caspase-12 trigger apoptosis in neonatal hypoxic-ischemic encephalopathy. Int J Clin Exp Pathol. 2015;8:6960-6 pubmed
    ..1% O2 compared with the cells treated with 20% O2. Furthermore, the caspase 12 activation was triggered when the cells treated with the 0.1% O2...
  7. Cai J, Kang Z, Liu W, Luo X, Qiang S, Zhang J, et al. Hydrogen therapy reduces apoptosis in neonatal hypoxia-ischemia rat model. Neurosci Lett. 2008;441:167-72 pubmed publisher
    ..These results indicated H2 administration after HI appeared to provide brain protection via inhibition of neuronal apoptosis. ..
  8. Lou L, Geng B, Chen Y, Yu F, Zhao J, Tang C. Endoplasmic reticulum stress involved in heart and liver injury in iron-loaded rats. Clin Exp Pharmacol Physiol. 2009;36:612-8 pubmed publisher
    ..The ER stress response was analysed by expression of glucose-response protein 78 (GRP78) and activation of caspase 12. 3. In chronic iron-loaded rats, iron levels in the heart and liver were higher, by approximately 2- and 7...
  9. Chen J, Qin J, Liu X, Han Y, Yang Z, Chang X, et al. Nitric oxide-mediated neuronal apoptosis in rats with recurrent febrile seizures through endoplasmic reticulum stress pathway. Neurosci Lett. 2008;443:134-9 pubmed publisher
    ..These results suggest that NO mediates neuronal apoptosis caused by recurrent FS, and that the ER stress pathway is involved in NO-mediated neuronal apoptosis. ..

More Information


  1. Larner S, Hayes R, McKinsey D, Pike B, Wang K. Increased expression and processing of caspase-12 after traumatic brain injury in rats. J Neurochem. 2004;88:78-90 pubmed
    ..Our results suggest that the caspase-12-mediated ER apoptotic pathway may play a role in rat TBI pathology independent of the receptor- or mitochondria-mediated apoptotic pathways. ..
  2. Dirks A, Leeuwenburgh C. Aging and lifelong calorie restriction result in adaptations of skeletal muscle apoptosis repressor, apoptosis-inducing factor, X-linked inhibitor of apoptosis, caspase-3, and caspase-12. Free Radic Biol Med. 2004;36:27-39 pubmed
    ..Calorie restriction is able to lower the apoptotic potential in aged skeletal muscle by altering several key apoptotic proteins toward cellular survival, thereby reducing the potential for sarcopenia. ..
  3. Shimoke K, Amano H, Kishi S, Uchida H, Kudo M, Ikeuchi T. Nerve growth factor attenuates endoplasmic reticulum stress-mediated apoptosis via suppression of caspase-12 activity. J Biochem. 2004;135:439-46 pubmed
    ..These results demonstrate that the inactivation of caspase-12 via the NGF-mediated PI3-K signaling pathway leads to inactivation of the caspase cascade including caspase-3 and -9. ..
  4. Zong W, Li C, Hatzivassiliou G, Lindsten T, Yu Q, Yuan J, et al. Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis. J Cell Biol. 2003;162:59-69 pubmed
    ..In wild-type cells, this is associated with caspase 12 cleavage that is abolished in bax-/-bak-/- cells...
  5. Haidara K, Marion M, Gascon Barre M, Denizeau F, Averill Bates D. Implication of caspases and subcellular compartments in tert-butylhydroperoxide induced apoptosis. Toxicol Appl Pharmacol. 2008;229:65-76 pubmed publisher
    ..This study demonstrates that caspase-9 and caspase-12 are activated in t-BHP-induced apoptosis in hepatocytes. We highlight the importance of subcellular compartments such as mitochondria, ER and nuclei in the apoptotic process. ..
  6. Sun Y, Liu G, Song T, Liu F, Kang W, Zhang Y, et al. Upregulation of GRP78 and caspase-12 in diastolic failing heart. Acta Biochim Pol. 2008;55:511-6 pubmed
    ..These results suggest that GRP78 and caspase-12 were upregulated in cardiomyocytes and ERS can contribute to cardiac myocyte apoptosis in the diastolic heart failure resulting from hypertension. ..
  7. Zhang G, Teng X, Liu Y, Cai Y, Zhou Y, Duan X, et al. Inhibition of endoplasm reticulum stress by ghrelin protects against ischemia/reperfusion injury in rat heart. Peptides. 2009;30:1109-16 pubmed publisher
    ..Ghrelin could protect the heart against I/R injury, at least in part, through inhibiting myocardial ERS. ..
  8. Sun H, Sun L, Li Y, Shao M, Cheng X, Ge N, et al. ACE-inhibitor suppresses the apoptosis induced by endoplasmic reticulum stress in renal tubular in experimental diabetic rats. Exp Clin Endocrinol Diabetes. 2009;117:336-44 pubmed publisher
    ..Increased tubular apoptosis in experimental diabetic rats is attenuated by blockade of the renin-angiotensin system with an ACE inhibitor, which might be in an association with reduced endoplasmic reticulum stress. ..
  9. Li G, Wang H, Jiang C. [Effects of edaravone on the expression of GRP78, Caspase-12, and neuron apoptosis in juvenile rat hippocampus after status convulsive]. Zhonghua Er Ke Za Zhi. 2011;49:53-9 pubmed
    ..These results suggest that edaravone may have protective effect against the hippocampal damage caused by status convulsive. ..
  10. Dlugos C. ATF6 and caspase 12 expression in Purkinje neurons in acute slices from adult, ethanol-fed rats. Brain Res. 2014;1577:11-20 pubmed publisher
    ..floating sections were stained with antibodies against activating transcription factor 6 (ATF6) or activated caspase 12 and calbindin...
  11. Kosuge Y, Imai T, Kawaguchi M, Kihara T, Ishige K, Ito Y. Subregion-specific vulnerability to endoplasmic reticulum stress-induced neurotoxicity in rat hippocampal neurons. Neurochem Int. 2008;52:1204-11 pubmed publisher
  12. Kubisch C, Sans M, Arumugam T, Ernst S, Williams J, Logsdon C. Early activation of endoplasmic reticulum stress is associated with arginine-induced acute pancreatitis. Am J Physiol Gastrointest Liver Physiol. 2006;291:G238-45 pubmed
    ..These results indicate that ER stress is an important early acinar cell event that likely contributes to the development of acute pancreatitis in the arginine model. ..
  13. Jang Y, Kendaiah S, Drew B, Phillips T, Selman C, Julian D, et al. Doxorubicin treatment in vivo activates caspase-12 mediated cardiac apoptosis in both male and female rats. FEBS Lett. 2004;577:483-90 pubmed
    ..Moreover, no major sex differences exist in apoptosis signaling transduction cascade due to doxorubicin treatment. ..
  14. Chung L, Ng Y. Age-related alterations in expression of apoptosis regulatory proteins and heat shock proteins in rat skeletal muscle. Biochim Biophys Acta. 2006;1762:103-9 pubmed
    ..The increased expression of the HSPs suggests a relationship between HSPs and the aging-related apoptotic process. ..
  15. Mehmeti I, Gurgul Convey E, Lenzen S, Lortz S. Induction of the intrinsic apoptosis pathway in insulin-secreting cells is dependent on oxidative damage of mitochondria but independent of caspase-12 activation. Biochim Biophys Acta. 2011;1813:1827-35 pubmed publisher
  16. Roy S, Sharom J, Houde C, Loisel T, Vaillancourt J, Shao W, et al. Confinement of caspase-12 proteolytic activity to autoprocessing. Proc Natl Acad Sci U S A. 2008;105:4133-8 pubmed publisher
  17. Wang G, Wang Y, Teng Y, Sun F, Xiang H, Liu J, et al. Protective Effects of Emodin-Induced Neutrophil Apoptosis via the Ca2+-Caspase 12 Pathway against SIRS in Rats with Severe Acute Pancreatitis. Biomed Res Int. 2016;2016:1736024 pubmed publisher
    ..These results suggest that emodin inhibits SIRS in rats with SAP by inducing circulating neutrophil apoptosis via the Ca2+-calpain 1-caspase 12-caspase 3 signaling pathway.
  18. Diaz Horta O, Kamagate A, Herchuelz A, Van Eylen F. Na/Ca exchanger overexpression induces endoplasmic reticulum-related apoptosis and caspase-12 activation in insulin-releasing BRIN-BD11 cells. Diabetes. 2002;51:1815-24 pubmed
  19. Huang Y, Li X, Wang Y, Wang H, Huang C, Li J. Endoplasmic reticulum stress-induced hepatic stellate cell apoptosis through calcium-mediated JNK/P38 MAPK and Calpain/Caspase-12 pathways. Mol Cell Biochem. 2014;394:1-12 pubmed publisher
  20. Wan S, Shi P, Zhang X, Gu C, Fan S. Stronger expression of CHOP and caspase 12 in diabetic spinal cord injury rats. Neurol Res. 2009;31:1049-55 pubmed publisher
    ..and 7 days, and the level of C/EBP homologous transcription factor protein (CHOP), a proapoptotic protein, and caspase 12 were determined by immunohistochemistry staining and real-time reverse transcription quantitative polymerase ..
  21. Lee W, Kim D, Boo J, Kim Y, Park I, Mook Jung I. ER stress-induced caspase-12 activation is inhibited by PKC in neuronal cells. Apoptosis. 2005;10:407-15 pubmed
    ..These results suggest that an ER stress induces the activation of caspase-12 via caspase-3, and that PKC regulates both caspase-12 and caspase-3 activations in Cas-12 cells. ..
  22. Arakawa T, Katada A, Shigyo H, Kishibe K, Adachi M, Nonaka S, et al. Electrical stimulation prevents apoptosis in denervated skeletal muscle. NeuroRehabilitation. 2010;27:147-54 pubmed publisher
    ..We proposed that electrical stimulation would be a potential treatment for preventing atrophy of denervated skeletal muscles. ..
  23. Chen Y, Tang Y, Xiang Y, Xie Y, Huang X, ZHANG Y. Shengmai injection improved doxorubicin-induced cardiomyopathy by alleviating myocardial endoplasmic reticulum stress and caspase-12 dependent apoptosis. Biomed Res Int. 2015;2015:952671 pubmed publisher
    ..05), accompanied with improved heart function. SMI could alleviate myocardial ER stress and caspase-12 dependent apoptosis, which subsequently helped to improve the heart function of rats with DOX-CM. ..
  24. Xu B, Wang F, Wu S, Deng Y, Liu W, Feng S, et al. ?-Synuclein is involved in manganese-induced ER stress via PERK signal pathway in organotypic brain slice cultures. Mol Neurobiol. 2014;49:399-412 pubmed publisher
    ..Moreover, alpha-synuclein protein was associated with Mn-induced activation of PERK signaling pathway. ..
  25. Cao Y, Hao Y, Liu Q, Wang J, Li H, Duan H. [The relationship between endoplasmic reticulum stress and its particular apoptosis way caspase-12 and apoptosis in renal cortex of diabetic rats]. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2011;27:236-40 pubmed
    ..There was no significant difference between group A and group B. Activation of endoplasmic reticulum stress may play an important role in the development of diabetic nephropathy. ..
  26. Badiola N, Penas C, Miñano Molina A, Barneda Zahonero B, Fadó R, Sánchez Opazo G, et al. Induction of ER stress in response to oxygen-glucose deprivation of cortical cultures involves the activation of the PERK and IRE-1 pathways and of caspase-12. Cell Death Dis. 2011;2:e149 pubmed publisher
    ..Processing of procaspase-12 was mediated by NMDA receptor and calpain activation. Moreover, our data suggest that caspase-12 activation is independent of the unfolded protein response activated by ER stress. ..
  27. Matzno S, Yasuda S, Kitada Y, Akiyoshi T, Tanaka N, Juman S, et al. Clofibrate-induced apoptosis is mediated by Ca2+-dependent caspase-12 activation. Life Sci. 2006;78:1892-9 pubmed
    ..Taken together, our findings indicate that the clofibrate-induced myopathy is triggered by Ca2+ influx, then activated cytosolic caspase-12 through calpain-independent cascade, and consequently caused apoptotic DNA fragmentation. ..
  28. Zhang H, Song L, Jia C, Lu Y. Effects of ATP sensitive potassium channel opener on the mRNA and protein expressions of caspase-12 after cerebral ischemia-reperfusion in rats. Neurosci Bull. 2008;24:7-12 pubmed publisher
    ..05). K(ATP) opener may protect neurons from apoptosis following the cerebral ischemia-reperfusion by inhibiting ER stress pathway. ..
  29. Sasaya H, Utsumi T, Shimoke K, Nakayama H, Matsumura Y, Fukunaga K, et al. Nicotine suppresses tunicamycin-induced, but not thapsigargin-induced, expression of GRP78 during ER stress-mediated apoptosis in PC12 cells. J Biochem. 2008;144:251-7 pubmed publisher
  30. Zhao Q, Hu X, Shao L, Wu G, Du J, Xia J. LipoxinA4 attenuates myocardial ischemia reperfusion injury via a mechanism related to downregulation of GRP-78 and caspase-12 in rats. Heart Vessels. 2014;29:667-78 pubmed publisher
    ..LXA4 downregulates the mRNA and protein expression of GRP-78 and caspase-12. LXA4 could play a role in myocardial protection via a mechanism related to downregulation of GRP-78 and caspase-12, and inhibition of apoptosis. ..
  31. Sakurazawa M, Katsura K, Saito M, Asoh S, Ohta S, Katayama Y. Mild hypothermia enhanced the protective effect of protein therapy with transductive anti-death FNK protein using a rat focal transient cerebral ischemia model. Brain Res. 2012;1430:86-92 pubmed publisher
  32. Zhao D, Liu Q, Ji Y, Wang G, He X, Tian W, et al. Correlation between nitric oxide and early brain injury after subarachnoid hemorrhage. Int J Neurosci. 2015;125:531-9 pubmed publisher
    ..NO was also correlated with caspase-12. Our results suggest that NO is involved in the pathophysiological events of EBI after SAH by increasing caspase-12, which results in neuronal apoptosis. ..
  33. Lakshmanan A, Harima M, Suzuki K, Soetikno V, Nagata M, Nakamura T, et al. The hyperglycemia stimulated myocardial endoplasmic reticulum (ER) stress contributes to diabetic cardiomyopathy in the transgenic non-obese type 2 diabetic rats: a differential role of unfolded protein response (UPR) signaling proteins. Int J Biochem Cell Biol. 2013;45:438-47 pubmed publisher
  34. Zhang A, Zhang J, Sun P, Yao C, Su C, Sui T, et al. EIF2alpha and caspase-12 activation are involved in oxygen-glucose-serum deprivation/restoration-induced apoptosis of spinal cord astrocytes. Neurosci Lett. 2010;478:32-6 pubmed publisher
    ..These results indicate that both the PERK/eIF2 alpha/ATF4 ISR and activation of caspase-12 may be involved in apoptosis of spinal cord astrocytes induced by OGSD/restoration. ..
  35. Szegezdi E, Duffy A, O Mahoney M, Logue S, Mylotte L, O BRIEN T, et al. ER stress contributes to ischemia-induced cardiomyocyte apoptosis. Biochem Biophys Res Commun. 2006;349:1406-11 pubmed
    ..Thus, we provide evidence that the ER can generate and propagate apoptotic signals in response to ischemic stress and this pathway is therefore a novel target for prevention of ischemia-mediated cardiomyocyte loss. ..
  36. Ohse T, Inagi R, Tanaka T, Ota T, Miyata T, Kojima I, et al. Albumin induces endoplasmic reticulum stress and apoptosis in renal proximal tubular cells. Kidney Int. 2006;70:1447-55 pubmed
    ..In conclusion, renal tubular cells exposed to high protein load suffer from ER stress. ER stress may subsequently lead to tubular damage by activation of caspase-12. ..
  37. Wei H, Zhang R, Jin H, Liu D, Tang X, Tang C, et al. Hydrogen sulfide attenuates hyperhomocysteinemia-induced cardiomyocytic endoplasmic reticulum stress in rats. Antioxid Redox Signal. 2010;12:1079-91 pubmed publisher
    ..Glucose-regulated protein 78 (GRP78), CHOP, and caspase 12 expressions by myocardial tissues and cleaved caspase 12 and p-eIF2alpha expressions by H9c2 cells were detected ..
  38. Crosby K, Connell B, Saleh T. Estrogen limits ischemic cell death by modulating caspase-12-mediated apoptotic pathways following middle cerebral artery occlusion. Neuroscience. 2007;146:1524-35 pubmed
  39. de la Cadena S, Hernández Fonseca K, Camacho Arroyo I, Massieu L. Glucose deprivation induces reticulum stress by the PERK pathway and caspase-7- and calpain-mediated caspase-12 activation. Apoptosis. 2014;19:414-27 pubmed publisher
    ..In addition, we show that calpain and caspase-7 are soon activated after GD and mediate caspase-12 activation and neuronal death. ..
  40. Wang P, Arjona A, Zhang Y, Sultana H, Dai J, Yang L, et al. Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I. Nat Immunol. 2010;11:912-9 pubmed publisher
  41. Shimoke K, Matsuki Y, Fukunaga K, Matsumura Y, Fujita E, Sugihara K, et al. Appearance of nuclear-sorted caspase-12 fragments in cerebral cortical and hippocampal neurons in rats damaged by autologous blood clot embolic brain infarctions. Cell Mol Neurobiol. 2011;31:795-802 pubmed publisher
    ..This result suggests that the fragmentation of caspase-12 and the subsequent nuclear translocation of these fragments are involved in the brain infarction process in rats. ..
  42. Mouw G, Zechel J, Gamboa J, Lust W, Selman W, Ratcheson R. Activation of caspase-12, an endoplasmic reticulum resident caspase, after permanent focal ischemia in rat. Neuroreport. 2003;14:183-6 pubmed
  43. Liu Y, Liu P, Liu C, Hu Y, Xu L, Mu Y, et al. [Proteomic analysis of proliferation and apoptosis in carbon tetrachloride induced rat liver fibrosis]. Zhonghua Gan Zang Bing Za Zhi. 2005;13:563-6 pubmed
    ..Proliferation and apoptosis related proteins are expressed dynamically in different stages of rat liver fibrosis induced by CCl4. ..
  44. Dong Y, Miao L, Hei L, Lin L, Ding H. Neuroprotective effects and impact on caspase-12 expression of tauroursodeoxycholic acid after acute spinal cord injury in rats. Int J Clin Exp Pathol. 2015;8:15871-8 pubmed
    ..05). TUDCA can inhibit the expression of caspase-12 in rat neurons after SCI, reduce cell apoptosis, and exert neuroprotective effects on rat secondary nerve injuries after SCI. ..
  45. Ikeuchi Y, Stegmuller J, Netherton S, Huynh M, Masu M, Frank D, et al. A SnoN-Ccd1 pathway promotes axonal morphogenesis in the mammalian brain. J Neurosci. 2009;29:4312-21 pubmed publisher
    ..These findings define a novel SnoN-Ccd1 link that promotes axonal growth in the mammalian brain, with important implications for axonal development and regeneration. ..
  46. Morishima N, Nakanishi K, Takenouchi H, Shibata T, Yasuhiko Y. An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12. J Biol Chem. 2002;277:34287-94 pubmed
    ..These data suggest that procaspase-9 is a substrate of caspase-12 and that ER stress triggers a specific cascade involving caspase-12, -9, and -3 in a cytochrome c-independent manner. ..
  47. Zhang Q, Liu J, Chen S, Liu J, Liu L, Liu G, et al. Caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress. Apoptosis. 2016;21:432-42 pubmed publisher
    ..We concluded that caspase-12 played an important role in stretch-induced apoptosis that is associated by endoplasmic reticulum stress by activating caspase-3. ..