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Advanced Oxidation Protein Products Induce G1/G0-Phase Arrest in Ovarian Granulosa Cells via the ROS-JNK/p38 MAPK-p21 Pathway in Premature Ovarian Insufficiency.
Zhou, Xing-Yu; Zhang, Jun; Li, Ying; Chen, Ying-Xue; Wu, Xiao-Min; Li, Xin; Zhang, Xiao-Fei; Ma, Lin-Zi; Yang, Yi-Zhen; Zheng, Ke-Ming; Liu, Yu-Dong; Wang, Zhe; Chen, Shi-Ling.
Afiliación
  • Zhou XY; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, No 1838 Guangzhou Northern Road, Guangzhou 510515, China.
  • Zhang J; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, No 1838 Guangzhou Northern Road, Guangzhou 510515, China.
  • Li Y; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, No 1838 Guangzhou Northern Road, Guangzhou 510515, China.
  • Chen YX; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, No 1838 Guangzhou Northern Road, Guangzhou 510515, China.
  • Wu XM; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, No 1838 Guangzhou Northern Road, Guangzhou 510515, China.
  • Li X; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, No 1838 Guangzhou Northern Road, Guangzhou 510515, China.
  • Zhang XF; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, No 1838 Guangzhou Northern Road, Guangzhou 510515, China.
  • Ma LZ; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, No 1838 Guangzhou Northern Road, Guangzhou 510515, China.
  • Yang YZ; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, No 1838 Guangzhou Northern Road, Guangzhou 510515, China.
  • Zheng KM; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, No 1838 Guangzhou Northern Road, Guangzhou 510515, China.
  • Liu YD; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, No 1838 Guangzhou Northern Road, Guangzhou 510515, China.
  • Wang Z; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, No 1838 Guangzhou Northern Road, Guangzhou 510515, China.
  • Chen SL; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, No 1838 Guangzhou Northern Road, Guangzhou 510515, China.
Oxid Med Cell Longev ; 2021: 6634718, 2021.
Article en En | MEDLINE | ID: mdl-34367464
The mechanism underlying the role of oxidative stress and advanced oxidation protein products (AOPPs) in the aetiology of premature ovarian insufficiency (POI) is poorly understood. Here, we investigated the plasma AOPP level in POI patients and the effects of AOPPs on granulosa cells both in vitro and in vivo. KGN cells were treated with different AOPP doses, and cell cycle distribution, intracellular reactive oxygen species (ROS), and protein expression levels were measured. Sprague-Dawley (SD) rats were treated daily with PBS, rat serum albumin, AOPP, or AOPP+ N-acetylcysteine (NAC) for 12 weeks to explore the effect of AOPPs on ovarian function. Plasma AOPP concentrations were significantly higher in both POI and biochemical POI patients than in controls and negatively correlated with anti-Müllerian hormone and the antral follicle count. KGN cells treated with AOPP exhibited G1/G0-phase arrest. AOPP induced G1/G0-phase arrest in KGN cells by activating the ROS-c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK)-p21 pathway. Pretreatment with NAC, SP600125, SB203580, and si-p21 blocked AOPP-induced G1/G0-phase arrest. In SD rats, AOPP treatment increased the proportion of atretic follicles, and NAC attenuated the adverse effects of AOPPs in the ovary. In conclusion, we provide mechanistic evidence that AOPPs may induce cell cycle arrest in granulosa cells via the ROS-JNK/p38 MAPK-p21 pathway and thus may be a novel biomarker of POI.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Insuficiencia Ovárica Primaria / Especies Reactivas de Oxígeno / Proteínas Quinasas JNK Activadas por Mitógenos / Proteínas Quinasas p38 Activadas por Mitógenos / Inhibidor p21 de las Quinasas Dependientes de la Ciclina / Puntos de Control del Ciclo Celular / Productos Avanzados de Oxidación de Proteínas Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Oxid Med Cell Longev Asunto de la revista: METABOLISMO Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Insuficiencia Ovárica Primaria / Especies Reactivas de Oxígeno / Proteínas Quinasas JNK Activadas por Mitógenos / Proteínas Quinasas p38 Activadas por Mitógenos / Inhibidor p21 de las Quinasas Dependientes de la Ciclina / Puntos de Control del Ciclo Celular / Productos Avanzados de Oxidación de Proteínas Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Oxid Med Cell Longev Asunto de la revista: METABOLISMO Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos