Up-regulation of Sirt1/miR-149-5p signaling may play a role in resveratrol induced protection against ischemia via p53 in rat brain |
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| Affiliation: | 1. Department of Pharmaceutics, Aditya Pharmacy College, Suramaplem, Gandepalli Mandal, East Godavari, Andhra Pradesh, 533437, India;2. Department of Biochemistry, Acharya Nagarjuna University, Nagarjuna Nagar, Guntur, Andhra Pradesh, 522510, India;3. Department of Biotechnology and Bioinformatics, School of life Sciences, University of Hyderabad, Hyderabad, Telangana, 500046, India;4. Department of Pharmaceutics, JSS College of Pharmacy, Ooty, Tamil Nadu 643001, India;5. Department of Biotechnology and Bioinformatics, School of life Sciences, University of Hyderabad, Hyderabad, 500046, Telangana, India;1. Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan;2. Department of Neurosurgery, Graduate School of Medicine, Osaka University, Japan;3. Department of Neurosurgery, Osaka International Cancer Institute, Osaka, Japan;4. WPI Immunology Frontier Research Center, Osaka University, Japan;5. Department of Molecular Pharmacology, National Institute of Neuroscience, National Center of Neurology and Neurology and Psychiatry, Kodaira, Japan;6. Department of Molecular Neuroscience, Graduate School of Frontier Biosciences, Osaka University, Japan;1. Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, South Korea;2. Department of Internal Medicine, Dongkang Hospital, Ulsan, South Korea;3. Department of Neurology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, South Korea;1. Department of Neurosciences, Reproductive and Odontostomatological Sciences, “Federico II” University, Naples, Italy;2. Department of Public Health, “Federico II” University, Naples, Italy;1. Department of Pharmacology and Neuroscience, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, United States;2. Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, United States;3. Department of Physiology and Pharmacology, Center for Neuroscience, West Virginia University Health Science Center, 1 Medical Center Drive, Morgantown, WV 26506, United States |
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| Abstract: | Micro-RNA(miRNA) are well studied small noncoding RNA, which plays a diverse role in the regulation of vital elements in cell survival and apoptosis. However, the functional significance of miRNAs after the pathogenesis of ischemic stroke remains unclear. The present study is designed to investigate the regulatory role of miR-149-5p on Sirtuin-1/p53 axis during ischemic-reperfusion-induced injury. Middle cerebral artery occlusion (MCAO) was performed by nylon monofilament for 60 min. Resveratrol was administered via intraperitoneal (IP) route, 30 min before the MCAO. Our study demonstrated that the miR-149-5p levels were markedly decreased at 24 h after ischemic-reperfusion (I/R) injury. Further, we observed decreased p53 protein expression and increased miR-149-5p activity on sirtuin1 (Sirt1) activation with resveratrol after 24 h following MCAO. Moreover, immunohistochemistry studies found that resveratrol treatment significantly decreased the immunoreactivity of p53 and caspase-3 on activation of Sirt1/miR149-5p axis. In conclusion, our findings suggest that miR-149-5p could play a regulatory role in neuronal cell death via Sirt1/p53 axis, which offers a new target for novel therapeutic interventions during acute ischemic stroke. |
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| Keywords: | Sirtuin-1 P53 MicroRNA-149-5p Caspase-3 Middle cerebral artery occlusion |
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