SFRP2 Improves Mitochondrial Dynamics and Mitochondrial Biogenesis, Oxidative Stress, and Apoptosis in Diabetic Cardiomyopathy

Background. The mitochondrial dynamics and mitochondrial biogenesis are essential for maintaining the bioenergy function of mitochondria in diabetic cardiomyopathy (DCM). Previous studies have revealed that secreted frizzled-related protein 2 (SFRP2) is beneficial against apoptosis and oxidative str...

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Autores principales:	Tianyi Ma, Xiaohui Huang, Haoxiao Zheng, Guolin Huang, Weiwen Li, Xinyue Liu, Jingjing Liang, Yue Cao, Yunzhao Hu, Yuli Huang
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/4f884f465e5f482482abd57bf85ffaa8
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spelling	oai:doaj.org-article:4f884f465e5f482482abd57bf85ffaa82021-11-22T01:10:36ZSFRP2 Improves Mitochondrial Dynamics and Mitochondrial Biogenesis, Oxidative Stress, and Apoptosis in Diabetic Cardiomyopathy1942-099410.1155/2021/9265016https://doaj.org/article/4f884f465e5f482482abd57bf85ffaa82021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/9265016https://doaj.org/toc/1942-0994Background. The mitochondrial dynamics and mitochondrial biogenesis are essential for maintaining the bioenergy function of mitochondria in diabetic cardiomyopathy (DCM). Previous studies have revealed that secreted frizzled-related protein 2 (SFRP2) is beneficial against apoptosis and oxidative stress. However, no research has confirmed whether SFRP2 regulates oxidative stress and apoptosis through mitochondrial function in DCM. Methods. Exposure of H9C2 cardiomyocytes in high glucose (HG) 25 mM and palmitic acid (PAL) 0.2 mM was used to simulate DCM in vitro. H9C2 cells with SFRP2 overexpression or SFRP2 knockdown were constructed and cultured under glucolipotoxicity or normal glucose conditions. An SD rat model of type 2 diabetes mellitus (T2DM) was generated using a high-fat diet combined with a low-dose STZ injection. Overexpression of SFRP2 in the rat model was generated by using an adeno-associated virus approach. CCK-8, TUNEL assay, and DHE staining were used to detect cell viability, and MitoTracker Red CMXRos was used to detect changes in mitochondrial membrane potential. We used qRT-PCR and western blot to further explore the mechanisms of SFRP2 regulating mitochondrial dynamics through the AMPK/PGC1-α pathway to improve diabetic cardiomyocyte injury. Results. Our results indicated that SFRP2 was significantly downregulated in H9C2 cells and cardiac tissues in T2DM conditions, accompanied by decreased expression of mitochondrial dysfunction. The mitochondrial membrane potential was reduced, and the cells were led to oxidative stress injury and apoptosis. Furthermore, the overexpression of SFRP2 could reverse apoptosis and promote mitochondrial function in T2DM conditions in vitro and in vivo. We also found that silencing endogenous SFRP2 could further promote glucolipotoxicity-induced mitochondrial dysfunction and apoptosis in cardiomyocytes, accompanied by downregulation of p-AMPK. Conclusion. SFRP2 exerted cardioprotective effects by salvaging mitochondrial function in an AMPK-PGC1-α-dependent manner, which modulates mitochondrial dynamics and mitochondrial biogenesis, reducing oxidative stress and apoptosis. SFRP2 may be a promising therapeutic biomarker in DCM.Tianyi MaXiaohui HuangHaoxiao ZhengGuolin HuangWeiwen LiXinyue LiuJingjing LiangYue CaoYunzhao HuYuli HuangHindawi LimitedarticleCytologyQH573-671ENOxidative Medicine and Cellular Longevity, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Tianyi Ma Xiaohui Huang Haoxiao Zheng Guolin Huang Weiwen Li Xinyue Liu Jingjing Liang Yue Cao Yunzhao Hu Yuli Huang SFRP2 Improves Mitochondrial Dynamics and Mitochondrial Biogenesis, Oxidative Stress, and Apoptosis in Diabetic Cardiomyopathy
description	Background. The mitochondrial dynamics and mitochondrial biogenesis are essential for maintaining the bioenergy function of mitochondria in diabetic cardiomyopathy (DCM). Previous studies have revealed that secreted frizzled-related protein 2 (SFRP2) is beneficial against apoptosis and oxidative stress. However, no research has confirmed whether SFRP2 regulates oxidative stress and apoptosis through mitochondrial function in DCM. Methods. Exposure of H9C2 cardiomyocytes in high glucose (HG) 25 mM and palmitic acid (PAL) 0.2 mM was used to simulate DCM in vitro. H9C2 cells with SFRP2 overexpression or SFRP2 knockdown were constructed and cultured under glucolipotoxicity or normal glucose conditions. An SD rat model of type 2 diabetes mellitus (T2DM) was generated using a high-fat diet combined with a low-dose STZ injection. Overexpression of SFRP2 in the rat model was generated by using an adeno-associated virus approach. CCK-8, TUNEL assay, and DHE staining were used to detect cell viability, and MitoTracker Red CMXRos was used to detect changes in mitochondrial membrane potential. We used qRT-PCR and western blot to further explore the mechanisms of SFRP2 regulating mitochondrial dynamics through the AMPK/PGC1-α pathway to improve diabetic cardiomyocyte injury. Results. Our results indicated that SFRP2 was significantly downregulated in H9C2 cells and cardiac tissues in T2DM conditions, accompanied by decreased expression of mitochondrial dysfunction. The mitochondrial membrane potential was reduced, and the cells were led to oxidative stress injury and apoptosis. Furthermore, the overexpression of SFRP2 could reverse apoptosis and promote mitochondrial function in T2DM conditions in vitro and in vivo. We also found that silencing endogenous SFRP2 could further promote glucolipotoxicity-induced mitochondrial dysfunction and apoptosis in cardiomyocytes, accompanied by downregulation of p-AMPK. Conclusion. SFRP2 exerted cardioprotective effects by salvaging mitochondrial function in an AMPK-PGC1-α-dependent manner, which modulates mitochondrial dynamics and mitochondrial biogenesis, reducing oxidative stress and apoptosis. SFRP2 may be a promising therapeutic biomarker in DCM.
format	article
author	Tianyi Ma Xiaohui Huang Haoxiao Zheng Guolin Huang Weiwen Li Xinyue Liu Jingjing Liang Yue Cao Yunzhao Hu Yuli Huang
author_facet	Tianyi Ma Xiaohui Huang Haoxiao Zheng Guolin Huang Weiwen Li Xinyue Liu Jingjing Liang Yue Cao Yunzhao Hu Yuli Huang
author_sort	Tianyi Ma
title	SFRP2 Improves Mitochondrial Dynamics and Mitochondrial Biogenesis, Oxidative Stress, and Apoptosis in Diabetic Cardiomyopathy
title_short	SFRP2 Improves Mitochondrial Dynamics and Mitochondrial Biogenesis, Oxidative Stress, and Apoptosis in Diabetic Cardiomyopathy
title_full	SFRP2 Improves Mitochondrial Dynamics and Mitochondrial Biogenesis, Oxidative Stress, and Apoptosis in Diabetic Cardiomyopathy
title_fullStr	SFRP2 Improves Mitochondrial Dynamics and Mitochondrial Biogenesis, Oxidative Stress, and Apoptosis in Diabetic Cardiomyopathy
title_full_unstemmed	SFRP2 Improves Mitochondrial Dynamics and Mitochondrial Biogenesis, Oxidative Stress, and Apoptosis in Diabetic Cardiomyopathy
title_sort	sfrp2 improves mitochondrial dynamics and mitochondrial biogenesis, oxidative stress, and apoptosis in diabetic cardiomyopathy
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/4f884f465e5f482482abd57bf85ffaa8
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SFRP2 Improves Mitochondrial Dynamics and Mitochondrial Biogenesis, Oxidative Stress, and Apoptosis in Diabetic Cardiomyopathy

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