{"title":"槲皮素对高浓度 CuSO4 诱导的猪卵巢颗粒细胞自噬和凋亡的影响","authors":"","doi":"10.1016/j.domaniend.2024.106881","DOIUrl":null,"url":null,"abstract":"<div><p>Copper is a vital micronutrient necessary for the maintenance of physiological functions. However, excessive amounts can lead to organ damage. Porcine ovarian granulosa cells are damaged by a high concentration of CuSO<sub>4</sub>, which can reduce the reproductive capacity of sows. Quercetin has shown remarkable efficacy in mitigating the harmful effects of heavy metals. Therefore, the aim of this study was to investigate the effects of a high concentration of CuSO<sub>4</sub> on autophagy and apoptosis in porcine ovarian granulosa cells and to explore whether quercetin can counteract these toxic effect. Cell morphology, and the mRNA expression levels of autophagy-related genes (<em>LC3-Ⅰ, ATG5, ATG7, ATG12, Beclin1, mTOR, LC3-Ⅱ</em> and <em>P62</em>) were significantly changed upon treatment with 200 and 400 µM CuSO<sub>4</sub>. Treatment with 200 µM CuSO<sub>4</sub> increased expression of P62 protein (<em>P</em><0.05), promoted LC3-Ⅰ to LC3-Ⅱ conversion (<em>P</em><0.05), and reduced PINK1 protein expression and the ATP content (<em>P</em><0.05). In addition, expression of Caspase3 protein was increased and TUNEL staining indicated that the number of apoptotic cells was increased. However, co-treatment with 10 µM quercetin significantly decreased expression of P62 and conversion of LC3-Ⅰ to LC3-Ⅱ. Furthermore, flow cytometric analysis revealed that addition of 10 µM quercetin significantly reduced apoptosis induced by a high concentration of CuSO<sub>4</sub>. In summary, the results indicate that a high concentration of CuSO<sub>4</sub> can trigger mitochondrial and autophagy dysfunction, activate mitochondrial apoptosis pathway, and exert cytotoxic effects. Quercetin can mitigate autophagy dysfunction, enhance autophagic processes, and alleviate apoptosis.</p></div>","PeriodicalId":11356,"journal":{"name":"Domestic animal endocrinology","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impact of quercetin on autophagy and apoptosis induced by a high concentration of CuSO4 in porcine ovarian granulosa cells\",\"authors\":\"\",\"doi\":\"10.1016/j.domaniend.2024.106881\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Copper is a vital micronutrient necessary for the maintenance of physiological functions. However, excessive amounts can lead to organ damage. Porcine ovarian granulosa cells are damaged by a high concentration of CuSO<sub>4</sub>, which can reduce the reproductive capacity of sows. Quercetin has shown remarkable efficacy in mitigating the harmful effects of heavy metals. Therefore, the aim of this study was to investigate the effects of a high concentration of CuSO<sub>4</sub> on autophagy and apoptosis in porcine ovarian granulosa cells and to explore whether quercetin can counteract these toxic effect. Cell morphology, and the mRNA expression levels of autophagy-related genes (<em>LC3-Ⅰ, ATG5, ATG7, ATG12, Beclin1, mTOR, LC3-Ⅱ</em> and <em>P62</em>) were significantly changed upon treatment with 200 and 400 µM CuSO<sub>4</sub>. Treatment with 200 µM CuSO<sub>4</sub> increased expression of P62 protein (<em>P</em><0.05), promoted LC3-Ⅰ to LC3-Ⅱ conversion (<em>P</em><0.05), and reduced PINK1 protein expression and the ATP content (<em>P</em><0.05). In addition, expression of Caspase3 protein was increased and TUNEL staining indicated that the number of apoptotic cells was increased. However, co-treatment with 10 µM quercetin significantly decreased expression of P62 and conversion of LC3-Ⅰ to LC3-Ⅱ. Furthermore, flow cytometric analysis revealed that addition of 10 µM quercetin significantly reduced apoptosis induced by a high concentration of CuSO<sub>4</sub>. In summary, the results indicate that a high concentration of CuSO<sub>4</sub> can trigger mitochondrial and autophagy dysfunction, activate mitochondrial apoptosis pathway, and exert cytotoxic effects. Quercetin can mitigate autophagy dysfunction, enhance autophagic processes, and alleviate apoptosis.</p></div>\",\"PeriodicalId\":11356,\"journal\":{\"name\":\"Domestic animal endocrinology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2024-08-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Domestic animal endocrinology\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0739724024000444\",\"RegionNum\":2,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"AGRICULTURE, DAIRY & ANIMAL SCIENCE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Domestic animal endocrinology","FirstCategoryId":"97","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0739724024000444","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"AGRICULTURE, DAIRY & ANIMAL SCIENCE","Score":null,"Total":0}
Impact of quercetin on autophagy and apoptosis induced by a high concentration of CuSO4 in porcine ovarian granulosa cells
Copper is a vital micronutrient necessary for the maintenance of physiological functions. However, excessive amounts can lead to organ damage. Porcine ovarian granulosa cells are damaged by a high concentration of CuSO4, which can reduce the reproductive capacity of sows. Quercetin has shown remarkable efficacy in mitigating the harmful effects of heavy metals. Therefore, the aim of this study was to investigate the effects of a high concentration of CuSO4 on autophagy and apoptosis in porcine ovarian granulosa cells and to explore whether quercetin can counteract these toxic effect. Cell morphology, and the mRNA expression levels of autophagy-related genes (LC3-Ⅰ, ATG5, ATG7, ATG12, Beclin1, mTOR, LC3-Ⅱ and P62) were significantly changed upon treatment with 200 and 400 µM CuSO4. Treatment with 200 µM CuSO4 increased expression of P62 protein (P<0.05), promoted LC3-Ⅰ to LC3-Ⅱ conversion (P<0.05), and reduced PINK1 protein expression and the ATP content (P<0.05). In addition, expression of Caspase3 protein was increased and TUNEL staining indicated that the number of apoptotic cells was increased. However, co-treatment with 10 µM quercetin significantly decreased expression of P62 and conversion of LC3-Ⅰ to LC3-Ⅱ. Furthermore, flow cytometric analysis revealed that addition of 10 µM quercetin significantly reduced apoptosis induced by a high concentration of CuSO4. In summary, the results indicate that a high concentration of CuSO4 can trigger mitochondrial and autophagy dysfunction, activate mitochondrial apoptosis pathway, and exert cytotoxic effects. Quercetin can mitigate autophagy dysfunction, enhance autophagic processes, and alleviate apoptosis.
期刊介绍:
Domestic Animal Endocrinology publishes scientific papers dealing with the study of the endocrine physiology of domestic animal species. Those manuscripts utilizing other species as models for clinical or production problems associated with domestic animals are also welcome.
Topics covered include:
Classical and reproductive endocrinology-
Clinical and applied endocrinology-
Regulation of hormone secretion-
Hormone action-
Molecular biology-
Cytokines-
Growth factors