14-3-3 Protein Protects Against Cardiac Endoplasmic Reticulum Stress (ERS) and ERS-Initiated Apoptosis in Experimental Diabetes
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- Sari Flori R.
- Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Japan Department of Pharmacology, Faculty of Medicine and Health Sciences, Syarif Hidayatullah Jakarta, State Islamic University, Indonesia
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- Watanabe Kenichi
- Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Japan
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- Thandavarayan Rajarajan A.
- Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Japan
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- Harima Meilei
- Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Japan
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- Zhang Shaosong
- Lightlab Imaging, Inc., USA
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- Muslin Anthony J.
- Center for Cardiovascular Research, John Milliken Department of Internal Medicine, Washington University School of Medicine, USA
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- Kodama Makoto
- First Department of Internal Medicine, Niigata University Graduate School of Medical and Dental Science, Japan
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- Aizawa Yoshifusa
- First Department of Internal Medicine, Niigata University Graduate School of Medical and Dental Science, Japan
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Diabetic cardiomyopathy and nephropathy induce endoplasmic reticulum stress (ERS) and ERS-initiated apoptosis. The primary function of 14-3-3 protein is to inhibit apoptosis, but the roles of this protein in protecting against cardiac ERS and apoptosis in the diabetic heart are largely unknown. In this study, we investigated the in vivo role of 14-3-3 protein in diabetic ERS and apoptosis using streptozotocin (STZ)-induced transgenic mice that showed cardiac-specific expression of a dominant negative (DN) 14-3-3η protein mutant. The expression levels of cardiac glucose-regulated protein (GRP) 78, inositol-requiring enzyme (Ire) 1α, and tumor necrosis factor receptor (TNFR)-associated factor (TRAF) 2 protein were significantly increased in the diabetic DN 14-3-3η mice compared with the diabetic wild-type. Moreover, cardiac apoptosis and the expression of CCAAT / enhancer binding protein homology protein (CHOP), caspase-12, and cleaved caspase-12 protein were significantly increased in the diabetic DN 14-3-3η mice. In conclusion, partial depletion of 14-3-3 protein in the diabetic heart exacerbates cardiac ERS and activates ERS-induced apoptosis pathways, at least in part, through the regulation of CHOP and caspase-12 via the Ire1α/TRAF2 pathway. The enhancement of 14-3-3 protein expression can be used as a novel protective therapy against ERS and ERS-initiated apoptosis in the diabetic heart.
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 113 (4), 325-334, 2010
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390282680156309888
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- NII論文ID
- 10027745962
- 130000301209
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- NII書誌ID
- AA11806667
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 10790566
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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