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Tetramethylpyrazine reverses high-glucose induced hypoxic effects by negatively regulating HIF-1α induced BNIP3 expression to ameliorate H9c2 cardiomyoblast apoptosis.

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机构： [1]Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan [2]College of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan [3]School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan [4]China Medical University Children’s Hospital, China Medical University, Taichung, Taiwan [5]Department of Biological Science and Technology, China Medical University, Taichung, Taiwan [6]Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan [7]Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan [8]Department of Cardiology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan 511518, Guangdong, China [9]Department of Biotechnology, Asia University, Taichung, Taiwan.

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关键词： HIF-1 Diabetes mellitus Food flavoring Caspase Hypoxia

摘要：

Diabetic patients are highly vulnerable to hypoxic injury, which is associated with hypoxia induced BNIP3 expression that subsequently activate apoptosis. Our previous research show that Tetramethylpyrazine (TMP), a food flavoring agent, represses the hypoxia induced BNIP3 expression attenuate myocardial apoptosis. In this study, we evaluate the effect of TMP to provide protection against hypoxia aggravated high-glucose associated cellular apoptosis. The cytoprotective effect of TMP against high glucose induced cellular damages was determined on embryo derived H9c2 cardiomyoblast cells that were subjected to 5% hypoxia for 24 h and subjected to different duration of 33 mM high glucose challenge. Further, the involvement of HIF-1α and BNIP3 in cellular damage and the mechanism of protection of TMP were determined by overexpression and silencing HIF-1α and BNIP3 protein expression. The results show that hypoxic effects on cell viability aggravates with high glucose challenge and this augmentative effect is mediated through BNIP3 in H9c2 cardiomyoblast cells. However, TMP administration effectively reversed the augmented HIF-1α levels and BNIP3 elevation. TMP improved the survival of H9c2 cells and effectively suppressed apoptosis in H9c2 cells. Further comparison on the effects of TMP on H9c2 cells challenged with high glucose and those challenged with hypoxia show that TMP precisely regulated the hypoxic intensified apoptotic effects in high-glucose condition. The results clearly show that flavoring agent-TMP attenuates cytotoxicity amplified by hypoxia challenge in high glucose condition by destabilizing HIF-1α. © The Author(s). 2020.

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出版当年[2019]版：

大类 | 3 区医学

小类 | 3 区营养学

最新[2025]版：

大类 | 2 区医学

小类 | 3 区营养学

第一作者：

第一作者机构： [1]Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

通讯作者：

通讯机构： [2]College of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan [7]Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan [9]Department of Biotechnology, Asia University, Taichung, Taiwan.

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Tetramethylpyrazine reverses high-glucose induced hypoxic effects by negatively regulating HIF-1α induced BNIP3 expression to ameliorate H9c2 cardiomyoblast apoptosis.

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