Melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS

Abstract Mitochondrial injury in granulosa cells (GCs) is associated with the pathophysiological mechanism of polycystic ovary syndrome (PCOS). Melatonin reduces the mitochondrial injury by enhancing SIRT1 (NAD-dependent deacetylase sirtuin-1), while the mechanism remains unclear. Mitochondrial memb...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Bo Zheng, Junan Meng, Yuan Zhu, Min Ding, Yuting Zhang, Jianjun Zhou
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Melatonin PCOS Akt SIRT1 mPTP Gynecology and obstetrics RG1-991
Acceso en línea:	https://doaj.org/article/4ac614385a26416387f1b71c8e4834f5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4ac614385a26416387f1b71c8e4834f5
record_format	dspace
spelling	oai:doaj.org-article:4ac614385a26416387f1b71c8e4834f52021-11-14T12:31:58ZMelatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS10.1186/s13048-021-00912-y1757-2215https://doaj.org/article/4ac614385a26416387f1b71c8e4834f52021-11-01T00:00:00Zhttps://doi.org/10.1186/s13048-021-00912-yhttps://doaj.org/toc/1757-2215Abstract Mitochondrial injury in granulosa cells (GCs) is associated with the pathophysiological mechanism of polycystic ovary syndrome (PCOS). Melatonin reduces the mitochondrial injury by enhancing SIRT1 (NAD-dependent deacetylase sirtuin-1), while the mechanism remains unclear. Mitochondrial membrane potential is a universal selective indicator of mitochondrial function. In this study, mitochondrial swelling and membrane defect mitochondria in granulosa cells were observed from PCOS patients and DHT-induced PCOS-like mice, and the cytochrome C level in the cytoplasm and the expression of BAX (BCL2-associated X protein) in mitochondria were significantly increased in GCs, with p-Akt decreased, showing mitochondrial membrane was damaged in GCs of PCOS. Melatonin treatment decreased mitochondrial permeability transition pore (mPTP) opening and increased the JC-1 (5,5′,6,6′-tetrachloro1,1′,3,3′-tetramethylbenzimidazolylcarbocyanine iodide) aggregate/monomer ratio in the live KGN cells treated with DHT, indicating melatonin mediates mPTP to increase mitochondrial membrane potential. Furthermore, we found melatonin decreased the levels of cytochrome C and BAX in DHT-induced PCOS mice. PDK1/Akt played an essential role in improving the mitochondrial membrane function, and melatonin treatment increased p-PDK 1 and p-Akt in vivo and in vitro. The SIRT1 was also increased with melatonin treatment, while knocking down SIRT1 mRNA inhibiting the protective effect of melatonin to activate PDK1/Akt. In conclusion, melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS.Bo ZhengJunan MengYuan ZhuMin DingYuting ZhangJianjun ZhouBMCarticleMelatoninPCOSAktSIRT1mPTPGynecology and obstetricsRG1-991ENJournal of Ovarian Research, Vol 14, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Melatonin PCOS Akt SIRT1 mPTP Gynecology and obstetrics RG1-991
spellingShingle	Melatonin PCOS Akt SIRT1 mPTP Gynecology and obstetrics RG1-991 Bo Zheng Junan Meng Yuan Zhu Min Ding Yuting Zhang Jianjun Zhou Melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS
description	Abstract Mitochondrial injury in granulosa cells (GCs) is associated with the pathophysiological mechanism of polycystic ovary syndrome (PCOS). Melatonin reduces the mitochondrial injury by enhancing SIRT1 (NAD-dependent deacetylase sirtuin-1), while the mechanism remains unclear. Mitochondrial membrane potential is a universal selective indicator of mitochondrial function. In this study, mitochondrial swelling and membrane defect mitochondria in granulosa cells were observed from PCOS patients and DHT-induced PCOS-like mice, and the cytochrome C level in the cytoplasm and the expression of BAX (BCL2-associated X protein) in mitochondria were significantly increased in GCs, with p-Akt decreased, showing mitochondrial membrane was damaged in GCs of PCOS. Melatonin treatment decreased mitochondrial permeability transition pore (mPTP) opening and increased the JC-1 (5,5′,6,6′-tetrachloro1,1′,3,3′-tetramethylbenzimidazolylcarbocyanine iodide) aggregate/monomer ratio in the live KGN cells treated with DHT, indicating melatonin mediates mPTP to increase mitochondrial membrane potential. Furthermore, we found melatonin decreased the levels of cytochrome C and BAX in DHT-induced PCOS mice. PDK1/Akt played an essential role in improving the mitochondrial membrane function, and melatonin treatment increased p-PDK 1 and p-Akt in vivo and in vitro. The SIRT1 was also increased with melatonin treatment, while knocking down SIRT1 mRNA inhibiting the protective effect of melatonin to activate PDK1/Akt. In conclusion, melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS.
format	article
author	Bo Zheng Junan Meng Yuan Zhu Min Ding Yuting Zhang Jianjun Zhou
author_facet	Bo Zheng Junan Meng Yuan Zhu Min Ding Yuting Zhang Jianjun Zhou
author_sort	Bo Zheng
title	Melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS
title_short	Melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS
title_full	Melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS
title_fullStr	Melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS
title_full_unstemmed	Melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS
title_sort	melatonin enhances sirt1 to ameliorate mitochondrial membrane damage by activating pdk1/akt in granulosa cells of pcos
publisher	BMC
publishDate	2021
url	https://doaj.org/article/4ac614385a26416387f1b71c8e4834f5
work_keys_str_mv	AT bozheng melatoninenhancessirt1toamelioratemitochondrialmembranedamagebyactivatingpdk1aktingranulosacellsofpcos AT junanmeng melatoninenhancessirt1toamelioratemitochondrialmembranedamagebyactivatingpdk1aktingranulosacellsofpcos AT yuanzhu melatoninenhancessirt1toamelioratemitochondrialmembranedamagebyactivatingpdk1aktingranulosacellsofpcos AT minding melatoninenhancessirt1toamelioratemitochondrialmembranedamagebyactivatingpdk1aktingranulosacellsofpcos AT yutingzhang melatoninenhancessirt1toamelioratemitochondrialmembranedamagebyactivatingpdk1aktingranulosacellsofpcos AT jianjunzhou melatoninenhancessirt1toamelioratemitochondrialmembranedamagebyactivatingpdk1aktingranulosacellsofpcos
_version_	1718429164503040000

Melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS

Ejemplares similares