Rosiglitazone ameliorates palmitic acid-induced endoplasmic reticulum stress and steroidogenic capacity in granulosa cells |
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| Institution: | 1. Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, P.O.Box: 1177, Urmia, Iran;2. Department of Surgery and Diagnostic Imaging, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran;3. Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran;1. Department of Obstetrics and Gynecology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey;2. Department of Obstetrics and Gynecology, Reyap Hospital Corlu, Tekirdag, Turkey;3. Department of Biochemistry, Yildiz Technical University, Istanbul, Turkey;4. Department of Biochemistry, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey;5. Department of Obstetrics and Gynecology, Memorial Bahcelievler Hospital, Istanbul, Turkey;6. Department of Physiology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey;1. Facility for Risk Assessment and Intervention Studies, Department of Pharmacology and Toxicology, India;2. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab, 160062, India;3. National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S Nagar, Punjab, 160062, India;4. National Toxicology Centre, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab, 160062, India;1. Faculty of Medicine, Universiti Teknologi MARA Sungai Buloh Campus, Selangor, Malaysia;2. I-PPerFORM, Universiti Teknologi MARA, Malaysia;1. Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China;2. Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, China;3. Department of Veterinary Anatomy & Histology, Shaheed Benazir Bhutto University of Veterinary and Animal Sciences, Sakrand, 67210, Sindh, Pakistan;4. Department of Veterinary Parasitology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China;5. Department of Veterinary Parasitology, Faculty of Veterinary Sciences, Shaheed Benazir Bhutto University of Veterinary and Animal Sciences, Sakrand, 67210, Sindh, Pakistan;1. Department of Physiology. University of the Basque Country (UPV/EHU), Leioa, Spain;2. Department of Biochemistry and Molecular Biology. University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain;3. Department of Biochemistry and Molecular Biology. University of Southern Denmark. Odense. Denmark;4. Center for Reproductive Medicine and Infertility Quirón Bilbao, Bilbao, Spain |
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| Abstract: | Granulosa cells play essential roles in follicular development, oocyte maturation and sex hormone secretion. The exposure of granulosa cells to palmitic acid (PA), the main component of dietary saturated fat, inhibits cell viability. However, the mechanism underlying PA-induced cytotoxicity in granulosa cells has not been deeply investigated. Rosiglitazone (RSG) is a member of the thiazolidinedione family and is reported to protect cells from cytotoxicity and endoplasmic reticulum (ER) stress in other cell types, but whether RSG protects granulosa cells remain unknown. In this study, KGN cell line and primary granulosa cells were used as models of granulosa cells to explore the effects of PA and RSG and the underlying mechanisms. The results showed that PA inhibits cell viability and estradiol secretion through inducing ER stress and cAMP/PKA/CREB pathway. CCAAT/enhancer-binding protein homologous protein (CHOP), an ER stress marker, was demonstrated to participate in PA-induced cytotoxicity. RSG treatment rescued granulosa cells from PA-induced cell death and ER stress. Moreover, RSG was identified to ameliorate ER stress induced by tunicamycin in granulosa cells. In addition, RSG treatment rescued granulosa cells from PA-induced decrease of estrogen secretion by cAMP/PKA/CREB pathway. In conclusion, RSG can protect granulosa cells against PA-induced cytotoxicity by inhibiting ER stress, and can recover steroidogenic capacity, indicating a potential use of RSG in the treatment of granulosa cell dysfunction. |
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| Keywords: | Rosiglitazone Palmitic acid ER stress cAMP pathway Granulosa cells |
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