Research Topics
Genomes and Genes
| Jun Ichi AbeSummaryAffiliation: University of Rochester Country: USA Publications
Research Grants
| Collaborators
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Detail Information
Publications
p90RSK targets the ERK5-CHIP ubiquitin E3 ligase activity in diabetic hearts and promotes cardiac apoptosis and dysfunctionNhat Tu Le
University of Rochester School of Medicine and Dentistry, Aab Cardiovascular Research Institute, 601 Elmwood Avenue, Rochester, NY 14642, USA
Circ Res 110:536-50. 2012..The regulatory mechanism governing ERK5/CHIP interaction is unknown...
Bcr in vascular smooth muscle cells involvement of Ras and Raf-1 activation by BcrJ I Abe
Center for Cardiovascular Research, University of Rochester, New York 14642, USA
Ann N Y Acad Sci 947:341-3. 2001..These results demonstrated the importance of Bcr in PDGF-mediated events such as activation of Ras, Raf-1, and ERK1/2 and stimulation of DNA synthesis...- PKCzeta decreases eNOS protein stability via inhibitory phosphorylation of ERK5Patrizia Nigro
Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642, USA
Blood 116:1971-9. 2010..Taken together our results show that PKCζ binds and phosphorylates ERK5, thereby decreasing eNOS protein stability and contributing to early events of atherosclerosis... - Regulation of epidermal growth factor-induced connexin 43 gap junction communication by big mitogen-activated protein kinase1/ERK5 but not ERK1/2 kinase activationScott J Cameron
Department of Pharmacology Physiology, University of Rochester Medical Center, Rochester, New York 14642, USA
J Biol Chem 278:18682-8. 2003..These data indicate that BMK1 is more important than ERK1/2 in EGF-mediated Cx43 gap junction uncoupling by association and Cx43 Ser- 255 phosphorylation... 
Extracellular signal-regulated kinase 5 SUMOylation antagonizes shear stress-induced antiinflammatory response and endothelial nitric oxide synthase expression in endothelial cellsChang Hoon Woo
Cardiovascular Research Institute, 601 Elmwood Ave, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
Circ Res 102:538-45. 2008..These data clearly defined SUMOylation-dependent ERK5 transcriptional repression independent of kinase activity and suggested this process as among the molecular mechanisms of diabetes-mediated endothelial dysfunction...- ERK1/2 associates with the c-Met-binding domain of growth factor receptor-bound protein 2 (Grb2)-associated binder-1 (Gab1): role in ERK1/2 and early growth response factor-1 (Egr-1) nuclear accumulationMasaki Osawa
Center for Cardiovascular Research, University of Rochester, Rochester, New York 14642, USA
J Biol Chem 279:29691-9. 2004..These data suggest that Gab1-ERK1/2 binding and their nuclear translocation play a crucial role in Egr-1 nuclear accumulation... - Role of p90 ribosomal S6 kinase (p90RSK) in reactive oxygen species and protein kinase C beta (PKC-beta)-mediated cardiac troponin I phosphorylationSeigo Itoh
Cardiovascular Research Institute, University of Rochester, Rochester, New York 14642, USA
J Biol Chem 280:24135-42. 2005..LY333,531, a specific PKCbeta inhibitor, inhibited both p90RSK and cTnI (Ser(23/24)) phosphorylation by H2O2. Taken together, our data support a new redox-sensitive mechanism regulating cTnI phosphorylation in cardiomyocytes... - Insulin-like growth factor-1 enhances inflammatory responses in endothelial cells: role of Gab1 and MEKK3 in TNF-alpha-induced c-Jun and NF-kappaB activation and adhesion molecule expressionWenyi Che
Center for Cardiovascular Research, University of Rochester, Rochester, NY, USA
Circ Res 90:1222-30. 2002..Furthermore, the IGF-1-mediated downregulation of Gab1 expression represents a novel mechanism to promote vascular inflammation and atherosclerosis... - Role of p90 ribosomal S6 kinase-mediated prorenin-converting enzyme in ischemic and diabetic myocardiumSeigo Itoh
Cardiovascular Research Institute, University of Rochester, Rochester, NY, USA
Circulation 113:1787-98. 2006.... - Vinpocetine inhibits NF-kappaB-dependent inflammation via an IKK-dependent but PDE-independent mechanismKye Im Jeon
Aab Cardiovascular Research Institute and Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
Proc Natl Acad Sci U S A 107:9795-800. 2010..These studies thus identify vinpocetine as a unique antiinflammatory agent that may be repositioned for the treatment of many inflammatory diseases... - Functional role of phosphodiesterase 3 in cardiomyocyte apoptosis: implication in heart failureBo Ding
Center for Cardiovascular Research, University of Rochester School of Medicine and Dentistry, Aab Institute of Biomedical Science, Rochester, NY 14642, USA
Circulation 111:2469-76. 2005..Although chronic treatment with PDE3 inhibitors increases mortality in patients with heart failure, the contribution of PDE3 expression/activity in heart failure is not well known... - Mitochondrial Dok-4 recruits Src kinase and regulates NF-kappaB activation in endothelial cellsSeigo Itoh
Center for Cardiovascular Research, University of Rochester, Rochester, New York 14642, USA
J Biol Chem 280:26383-96. 2005..These data suggest a role for mitochondrial Dok-4 as an anchoring molecule for the tyrosine kinase c-Src, and in turn as a regulator of TNF-alpha-mediated ROS production and NF-kappaB activation... - Differential role of MEK5alpha and MEK5beta in BMK1/ERK5 activationScott J Cameron
Department of Pharmacology Physiology, Center for Cardiovascular Research, Department of Anesthesiology, University of Rochester Medical Center, Rochester, New York 14642, USA
J Biol Chem 279:1506-12. 2004..These data suggest that alternative splicing of MEK5alpha and MEK5beta may play a critical role in BMK1 activation and subsequent cell proliferation... - Cyclophilin A is an inflammatory mediator that promotes atherosclerosis in apolipoprotein E-deficient micePatrizia Nigro
Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
J Exp Med 208:53-66. 2011..These data define a role for CyPA in atherosclerosis and suggest CyPA as a target for cardiovascular therapies... - Ca2+/calmodulin-stimulated PDE1 regulates the beta-catenin/TCF signaling through PP2A B56 gamma subunit in proliferating vascular smooth muscle cellsKye Im Jeon
Aab Cardiovascular Research Institute, University of Rochester Medical Center, Rochester, NY 14642, USA
FEBS J 277:5026-39. 2010..Taken together, these findings provide direct evidence for the first time that PP2A B56γ is a critical mediator for PDE1A in the regulation of β-catenin signaling in proliferating VSMCs... - Novel role of C terminus of Hsc70-interacting protein (CHIP) ubiquitin ligase on inhibiting cardiac apoptosis and dysfunction via regulating ERK5-mediated degradation of inducible cAMP early repressorChang Hoon Woo
Aab Cardiovascular Research Institute, University of Rochester, Rochester, New York 14642, USA
FASEB J 24:4917-28. 2010..We identified ICER as a novel CHIP substrate and that the ERK5-CHIP complex plays an obligatory role in inhibition of ICER expression, cardiomyocyte apoptosis, and cardiac dysfunction... - Activation of extracellular signal-regulated kinase 5 reduces cardiac apoptosis and dysfunction via inhibition of a phosphodiesterase 3A/inducible cAMP early repressor feedback loopChen Yan
Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
Circ Res 100:510-9. 2007..These data suggest a new therapeutic paradigm for end stage of heart failure by inhibiting the PDE3A/ICER feedback loop via activating ERK5... - Protein kinase C-alpha and protein kinase C-epsilon are required for Grb2-associated binder-1 tyrosine phosphorylation in response to platelet-derived growth factorYuji Saito
Center for Cardiovascular Research, University of Rochester, Rochester, New York 14642, USA
J Biol Chem 277:23216-22. 2002..Because PDGF-mediated ERK activation is enhanced in Chinese hamster ovary cells that overexpress Gab1, Gab1 serves as an important link between PKC and ERK activation by PDGFbeta receptors in VSMC... - MK2 SUMOylation regulates actin filament remodeling and subsequent migration in endothelial cells by inhibiting MK2 kinase and HSP27 phosphorylationEugene Chang
Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Rochester, NY 14642, USA
Blood 117:2527-37. 2011..Our study shows that MK2 SUMOylation is a new mechanism for regulating actin filament dynamics in ECs... - Reactive oxygen species-induced activation of p90 ribosomal S6 kinase prolongs cardiac repolarization through inhibiting outward K+ channel activityZhibo Lu
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
Circ Res 103:269-78. 2008..These findings indicate that p90RSK activation is critical for reactive oxygen species-mediated inhibition of voltage-gated K+ channel activity and leads to prolongation of cardiac repolarization... - PKCζ mediates disturbed flow-induced endothelial apoptosis via p53 SUMOylationKyung Sun Heo
Aab Cardiovascular Research Institute, University of Rochester, Rochester, NY 14642, USA
J Cell Biol 193:867-84. 2011..We propose a novel mechanism for p53 SUMOylation mediated by the PKCζ-PIASy interaction during d-flow-mediated EC apoptosis, which has potential relevance to early events of atherosclerosis... - Inhibiting p90 ribosomal S6 kinase prevents (Na+)-H+ exchanger-mediated cardiac ischemia-reperfusion injuryNaoya Maekawa
Cardiovascular Research Institute, Department of Medicine, University of Rochester, Rochester, NY, USA
Circulation 113:2516-23. 2006..Therefore, we hypothesized that inhibiting RSK in cardiomyocytes would prevent NHE1 activation and decrease I/R-mediated injury... - p90 ribosomal S6 kinase regulates activity of the renin-angiotensin system: a pathogenic mechanism for ischemia-reperfusion injuryXi Shi
Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14620, USA
J Mol Cell Cardiol 51:272-5. 2011..Thus, renin inhibition may provide an alternative therapeutic strategy under conditions of increased RAS... - A positive feedback loop of phosphodiesterase 3 (PDE3) and inducible cAMP early repressor (ICER) leads to cardiomyocyte apoptosisBo Ding
Cardiovascular Research Institute, Department of Pathology, University of Rochester, Rochester, NY 14642, USA
Proc Natl Acad Sci U S A 102:14771-6. 2005..Our findings may provide a therapeutic paradigm to prevent cardiomyocyte apoptosis and the progression of heart failure by inhibiting the PDE3A-ICER feedback loop... - Role of Ca2+/calmodulin-stimulated cyclic nucleotide phosphodiesterase 1 in mediating cardiomyocyte hypertrophyClint L Miller
Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, NY 14642, USA
Circ Res 105:956-64. 2009..Ca(2+)/calmodulin (CaM)-activated cGMP-hydrolyzing PDE1 family may play a pivotal role in balancing intracellular Ca(2+)/CaM and cGMP signaling; however, its function in cardiomyocytes is unknown... - Flow shear stress and atherosclerosis: a matter of site specificityPatrizia Nigro
Department of Medicine, Aab Cardiovascular Research Institute, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA
Antioxid Redox Signal 15:1405-14. 2011..The targeted modulation of proteins activated in a site-specific manner holds the promise for a new approach to limit atherosclerosis... - Flow antagonizes TNF-alpha signaling in endothelial cells by inhibiting caspase-dependent PKC zeta processingGwenaele Garin
University of Rochester, Cardiovascular Research Institute, Box 679, 601 Elmwood Avenue, Rochester, NY 14642, USA
Circ Res 101:97-105. 2007..These results define a novel role for PKCzeta as a shared signaling mediator for flow and TNF-alpha, and important for flow-mediated inhibition of proinflammatory and apoptotic events in ECs... - SUMO--a post-translational modification with therapeutic potential?Chang Hoon Woo
Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box CVRI, Rochester, NY 14642, United States
Curr Opin Pharmacol 10:146-55. 2010..These findings support the idea that ERK5-sumoylation is a novel therapeutic target for the treatment of diabetes-related cardiovascular diseases... - Central role of endogenous Toll-like receptor-2 activation in regulating inflammation, reactive oxygen species production, and subsequent neointimal formation after vascular injuryTetsuro Shishido
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Japan
Biochem Biophys Res Commun 345:1446-53. 2006..Here, we report that vascular injury-mediated cytokine expression, reactive oxygen species (ROS) production, as well as subsequent neointimal formation requires Toll-like receptor-2 (TLR-2) mediated signaling pathway in vivo... - Bcr kinase activation by angiotensin II inhibits peroxisome-proliferator-activated receptor gamma transcriptional activity in vascular smooth muscle cellsJeffrey D Alexis
Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
Circ Res 104:69-78. 2009.... - Regulation of phosphodiesterase 3 and inducible cAMP early repressor in the heartChen Yan
Center for Cardiovascular Research, Aab Institute of Biomedical Science, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
Circ Res 100:489-501. 2007..Hence, strategies that maintain PDE3A function may represent an attractive approach to circumvent myocyte apoptosis and cardiac dysfunction... - Fluid shear stress inhibits TNF-mediated JNK activation via MEK5-BMK1 in endothelial cellsLingli Li
Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine and Dentistry, Box 706, 601 Elmwood Avenue, Rochester, NY 14642, USA
Biochem Biophys Res Commun 370:159-63. 2008..These results support a key role for the MEK5-BMK1 signaling pathway in the atheroprotective effects of blood flow... - Disturbed-flow-mediated vascular reactive oxygen species induce endothelial dysfunctionKyung Sun Heo
Aab Cardiovascular Research Institute, University of Rochester, NY, USA
Circ J 75:2722-30. 2011..In addition, we highlight several mechanisms contributing to endothelial dysfunction, focusing on the relations between flow patterns and activation of reactive oxygen species generating enzymes... - TR4 nuclear receptor functions as a fatty acid sensor to modulate CD36 expression and foam cell formationShaozhen Xie
George Whipple Lab for Cancer Research, Department of Pathology, and Cardiovascular Research Institute, University of Rochester Medical Center, Rochester, NY 14642, USA
Proc Natl Acad Sci U S A 106:13353-8. 2009.... - Effects of MEK5/ERK5 association on small ubiquitin-related modification of ERK5: implications for diabetic ventricular dysfunction after myocardial infarctionTetsuro Shishido
Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, West Henrietta, NY 14586, USA
Circ Res 102:1416-25. 2008..These results demonstrated that ERK5 transcriptional activity is subject to downregulation by diabetes-dependent SUMOylation, which resulted in a proapoptotic condition contributing to poor post-MI LV function... - Cyclophilin A enhances vascular oxidative stress and the development of angiotensin II-induced aortic aneurysmsKimio Satoh
Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
Nat Med 15:649-56. 2009..These data define a previously undescribed role for CypA in AAA formation and suggest CypA as a new target for treating cardiovascular disease... - Activation of big MAP kinase 1 (BMK1/ERK5) inhibits cardiac injury after myocardial ischemia and reperfusionScott J Cameron
Department of Pharmacology/Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA
FEBS Lett 566:255-60. 2004..We propose a novel role for BMK1 in protecting the heart from ischemia/reperfusion-induced cardiac injury... - ERK5 activation inhibits inflammatory responses via peroxisome proliferator-activated receptor delta (PPARdelta) stimulationChang-Hoon Woo
Cardiovascular Research Institute, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA
J Biol Chem 281:32164-74. 2006..Based on these data, we propose a new mechanism by which CO and HO-1 mediate anti-inflammatory effects via activating ERK5/PPARdelta, and ERK5 mediates CO and HO-1-induced PPARdelta activation via its interaction with PPARdelta... - Activation of mitogen-activated protein kinases and p90 ribosomal S6 kinase in failing human hearts with dilated cardiomyopathyYasuchika Takeishi
Department of Medicine, Case Western Reserve University, Cleveland, OH 44106 5029, USA
Cardiovasc Res 53:131-7. 2002..However, the abundance and activity of these kinases in human hearts are unknown... - Cyclophilin A mediates vascular remodeling by promoting inflammation and vascular smooth muscle cell proliferationKimio Satoh
Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Rochester, NY 14642, USA
Circulation 117:3088-98. 2008.... - Cardiac-specific overexpression of diacylglycerol kinase zeta prevents Gq protein-coupled receptor agonist-induced cardiac hypertrophy in transgenic miceTakanori Arimoto
First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan
Circulation 113:60-6. 2006..We hypothesized that DGK might prevent GPCR agonist-induced activation of diacylglycerol downstream signaling cascades and subsequent cardiac hypertrophy... - Fluid shear stress activates proline-rich tyrosine kinase via reactive oxygen species-dependent pathwayLung-Kuo Tai
Center for Cardiovascular Research, University of Rochester, Rochester, NY 14642, USA
Arterioscler Thromb Vasc Biol 22:1790-6. 2002..CONCLUSIONS: These results show a redox-sensitive pathway for flow-mediated activation of nonreceptor tyrosine kinase activity that requires ROS and intracellular calcium, but not Src kinase... - Stress and vascular responses: atheroprotective effect of laminar fluid shear stress in endothelial cells: possible role of mitogen-activated protein kinasesMasanori Yoshizumi
Department of Pharmacology, The University of Tokushima School of Medicine, Tokushima, Japan
J Pharmacol Sci 91:172-6. 2003..Understanding the mechanisms by which steady laminar flow regulates JNK activation by cytokines may provide insight into the atheroprotective mechanisms induced by laminar blood flow... - Role of phosphodiesterase 3 in NO/cGMP-mediated antiinflammatory effects in vascular smooth muscle cellsToru Aizawa
University of Rochester, Center for Cardiovascular Research, 601 Elmwood Ave, Box 679, Rochester, NY 14642, USA
Circ Res 93:406-13. 2003..These results suggest that SNAP and CNP exert inhibitory effects on NF-kappaB-dependent transcription by activation of PKA via cGMP-dependent inhibition of PDE3 activity. Therefore, PDE3 is a novel mediator of inflammation in VSMCs... - Inhibition of tumor necrosis factor-[alpha]-induced SHP-2 phosphatase activity by shear stress: a mechanism to reduce endothelial inflammationNicole Lerner-Marmarosh
Center for Cardiovascular Research, University of Rochester, NY 14642, USA
Arterioscler Thromb Vasc Biol 23:1775-81. 2003.... - Protease-activated receptor-1 contributes to cardiac remodeling and hypertrophyRafal Pawlinski
The Scripps Research Institute, Department of Immunology, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
Circulation 116:2298-306. 2007..The purpose of the present study was to investigate the role of PAR-1 in infarction, cardiac remodeling, and hypertrophy after I/R injury. In addition, we analyzed the effect of overexpression of PAR-1 on cardiomyocytes... - The hinge-helix 1 region of peroxisome proliferator-activated receptor gamma1 (PPARgamma1) mediates interaction with extracellular signal-regulated kinase 5 and PPARgamma1 transcriptional activation: involvement in flow-induced PPARgamma activation in endMasashi Akaike
Center for Cardiovascular Research, 601 Elmwood Ave, Box 679, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
Mol Cell Biol 24:8691-704. 2004..These data suggest that ERK5 mediates flow- and ligand-induced PPARgamma activation via the interaction of ERK5 with the hinge-helix 1 region of PPARgamma... - Adenovirus-mediated overexpression of diacylglycerol kinase-zeta inhibits endothelin-1-induced cardiomyocyte hypertrophyHiroki Takahashi
First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan
Circulation 111:1510-6. 2005..Because DGK inactivates DAG, a strong activator of protein kinase C (PKC), we hypothesized that DGK inhibited ET-1-induced activation of a DAG-PKC signaling cascade and subsequent cardiomyocyte hypertrophy... - BMK1/ERK5 is a novel regulator of angiogenesis by destabilizing hypoxia inducible factor 1alphaXinchun Pi
Cardiovascular Research Institute, Department of Medicine, University of Rochester, NY, USA
Circ Res 96:1145-51. 2005..In summary, BMK1 is a novel negative regulator of HIF1alpha and angiogenesis by increasing HIF1alpha ubiquitination and inhibiting HIF1alpha activity in endothelial cells... - Perlecan proteolysis induces an alpha2beta1 integrin- and Src family kinase-dependent anti-apoptotic pathway in fibroblasts in the absence of focal adhesion kinase activationPatrick Laplante
Centre de recherche du Centre Hospitalier de l Universite de Montreal, University of Montreal, 1560 Sherbrooke East, Montreal, Quebec H2L 4M1, Canada
J Biol Chem 281:30383-92. 2006..In the long term, additional SFK members are recruited for sustaining the anti-apoptotic response, which could play crucial roles in abnormal fibrogenic healing... - Role of PKCs and NF-kappaB activation in myocardial inflammation: enemy or ally?Jun Ichi Abe
J Mol Cell Cardiol 43:404-8. 2007 - The novel role of the C-terminal region of SHP-2. Involvement of Gab1 and SHP-2 phosphatase activity in Elk-1 activationQunhua Huang
Center for Cardiovascular Research, University of Rochester, Rochester, New York 14642, USA
J Biol Chem 277:29330-41. 2002..Furthermore, we identified a novel sequence for SHP-2/Gab1 interactions in the C-terminal region of SHP-2...
Research Grants
- Kinases-mediated SUMOylation in Diabetic CardiomyopathyJay Yang; Fiscal Year: 2010..Moreover, we believe that our novel small molecule specific p90RSK inhibitor should provide a new therapeutic strategy for reducing post- ischemic cardiac dysfunction in diabetics. ..
- PPARgamma, Endothelial Inflammation and AtherosclerosisJun Ichi Abe; Fiscal Year: 2004..These experiments will provide a new molecular mechanism for the anti-inflammatory effect of PPARgamma and flow associated with ERK5 activity. ..
- ROLE OF P90RSK IN DIABETIC CARDIOMYOPATHYJun Ichi Abe; Fiscal Year: 2003..These results of these experiments will provide a molecular mechanism for the cardiac dysfunction associated with increased PKC activity, based on phosphorylation of TnI by p90RSK. ..
- BCR KINASE IN PDGF-MED EFFECTS IN VASCULAR SMOOTH MUSCLEJun Ichi Abe; Fiscal Year: 2002..We propose that Bcr is a novel downstream component of PDGF receptor signaling in vascular smooth muscle, and may be a candidate gene responsible for the atherosclerosis and restenosis. ..
- p90RSK: A flow responsive mediator of inflammationKeigi Fujiwara; Fiscal Year: 2010..These studies should provide insight into mechanisms by which disturbed flow promotes vascular inflammation and facilitate development of new therapeutic approaches to limit atherosclerosis, especially in DM. ..