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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.7
- 수록면
- 457 - 465 (9page)
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Streptozotocin (STZ)-induced murine models of type 1 diabetes have been used to examine ER stress during pancreatic β-cell apoptosis, as this ER stress plays important roles in the pathogenesis and development of the disease. However, the mechanisms linking type 1 diabetes to the ER stress-modulating anti-diabetic signaling pathway remain to be addressed, though it was recently established that ERK5 (Extracellular-signal-regulated kinase 5) contributes to the pathogeneses of diabetic complications. This study was undertaken to explore the mechanism whereby ERK5 inhibition instigates pancreatic β-cell apoptosis via an ER stress-dependent signaling pathway. STZ-induced diabetic WT and CHOP deficient mice were i.p. injected every 2 days for 6 days under BIX02189 (a specific ERK5 inhibitor) treatment in order to evaluate the role of ERK5. Hyperglycemia was exacerbated by co-treating C57BL/6J mice with STZ and BIX02189 as compared with mice administered with STZ alone. In addition, immunoblotting data revealed that ERK5 inhibition activated the unfolded protein response pathway accompanying apoptotic events, such as, PARP-1 and caspase-3 cleavage. Interestingly, ERK5 inhibition-induced exacerbation of pancreatic β-cell apoptosis was inhibited in CHOP deficient mice. Moreover, transduction of adenovirus encoding an active mutant form of MEK5α, an upstream kinase of ERK5, inhibited STZ-induced unfolded protein responses and β-cell apoptosis. These results suggest that ERK5 protects against STZ-induced pancreatic β-cell apoptosis and hyperglycemia by interrupting the ER stress-mediated apoptotic pathway.
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참고문헌 (31)
참고문헌 신청
Ahn, C. / 2015 / Streptozotocin induces endoplasmic reticulum stress and apoptosis via disruption of calcium homeostasis in mouse pancreas / Mol. Cell. Endocrinol 412:302~308
Apostolou, I. / 2003 / Effective destruction of Fas-deficient insulin-producing beta cells in type 1 diabetes / J. Exp. Med 198:1103~1106
Araki, E. / 2003 / Impact of endoplasmic reticulum stress pathway on pancreatic beta-cells and diabetes mellitus / Exp. Biol. Med 228:1213~1217
Dai, R. Y. / 2010 / PI3K/Akt promotes GRP78 accumulation and inhibits endoplasmic reticulum stress-induced apoptosis in HEK293 cells / Folia Biol 56:37~46
Eizirik, D. L. / 2008 / The role for endoplasmic reticulum stress in diabetes mellitus / Endocrine Rev 29:42~61
Apostolou, I. / 2003 / Effective destruction of Fas-deficient insulin-producing beta cells in type 1 diabetes / J. Exp. Med 198:1103~1106
Araki, E. / 2003 / Impact of endoplasmic reticulum stress pathway on pancreatic beta-cells and diabetes mellitus / Exp. Biol. Med 228:1213~1217
Dai, R. Y. / 2010 / PI3K/Akt promotes GRP78 accumulation and inhibits endoplasmic reticulum stress-induced apoptosis in HEK293 cells / Folia Biol 56:37~46
Eizirik, D. L. / 2008 / The role for endoplasmic reticulum stress in diabetes mellitus / Endocrine Rev 29:42~61
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