Resveratrol reduces RVLM neuron activity via activating the AMPK/Sirt3 pathway in stress-induced hypertension
Neuronal hyperexcitability in the rostral ventrolateral medulla (RVLM), driven by oxidative stress, plays a crucial role in stress-induced hypertension (SIH). While resveratrol (RSV) is known for its antioxidant properties, its effects on RVLM neurons in SIH remain unclear. We investigated this usin...
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| Published in | The Journal of biological chemistry Vol. 301; no. 4; p. 108394 |
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| Main Authors | , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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United States
Elsevier Inc
01.04.2025
American Society for Biochemistry and Molecular Biology |
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| Abstract | Neuronal hyperexcitability in the rostral ventrolateral medulla (RVLM), driven by oxidative stress, plays a crucial role in stress-induced hypertension (SIH). While resveratrol (RSV) is known for its antioxidant properties, its effects on RVLM neurons in SIH remain unclear. We investigated this using an SIH rat model exposed to electric foot shocks and noise stimulation for 15 days. Analysis of RVLM tissue revealed increased mitochondrial damage, oxidative stress, apoptosis, and dysregulated ferroptosis in SIH rats. RSV microinjection into the RVLM reduced blood pressure, sympathetic vascular tone, and neuronal excitability. Both in vivo and in vitro studies showed that RSV treatment alleviated mitochondrial oxidative stress, apoptosis, and ferroptosis through AMPK activation and subsequent Sirt3 upregulation. These therapeutic effects were blocked by either AMPK inhibition or Sirt3 knockdown. Our findings demonstrate that RSV attenuates SIH by activating the AMPK/Sirt3 pathway, thereby reducing RVLM oxidative stress and cell death. |
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| AbstractList | Neuronal hyperexcitability in the rostral ventrolateral medulla (RVLM), driven by oxidative stress, plays a crucial role in stress-induced hypertension (SIH). While resveratrol (RSV) is known for its antioxidant properties, its effects on RVLM neurons in SIH remain unclear. We investigated this using an SIH rat model exposed to electric foot shocks and noise stimulation for 15 days. Analysis of RVLM tissue revealed increased mitochondrial damage, oxidative stress, apoptosis, and dysregulated ferroptosis in SIH rats. RSV microinjection into the RVLM reduced blood pressure, sympathetic vascular tone, and neuronal excitability. Both in vivo and in vitro studies showed that RSV treatment alleviated mitochondrial oxidative stress, apoptosis, and ferroptosis through AMPK activation and subsequent Sirt3 upregulation. These therapeutic effects were blocked by either AMPK inhibition or Sirt3 knockdown. Our findings demonstrate that RSV attenuates SIH by activating the AMPK/Sirt3 pathway, thereby reducing RVLM oxidative stress and cell death. Neuronal hyperexcitability in the rostral ventrolateral medulla (RVLM), driven by oxidative stress, plays a crucial role in stress-induced hypertension (SIH). While resveratrol (RSV) is known for its antioxidant properties, its effects on RVLM neurons in SIH remain unclear. We investigated this using an SIH rat model exposed to electric foot shocks and noise stimulation for 15 days. Analysis of RVLM tissue revealed increased mitochondrial damage, oxidative stress, apoptosis, and dysregulated ferroptosis in SIH rats. RSV microinjection into the RVLM reduced blood pressure, sympathetic vascular tone, and neuronal excitability. Both in vivo and in vitro studies showed that RSV treatment alleviated mitochondrial oxidative stress, apoptosis, and ferroptosis through AMPK activation and subsequent Sirt3 upregulation. These therapeutic effects were blocked by either AMPK inhibition or Sirt3 knockdown. Our findings demonstrate that RSV attenuates SIH by activating the AMPK/Sirt3 pathway, thereby reducing RVLM oxidative stress and cell death. Neuronal hyperexcitability in the rostral ventrolateral medulla (RVLM), driven by oxidative stress, plays a crucial role in stress-induced hypertension (SIH). While resveratrol (RSV) is known for its antioxidant properties, its effects on RVLM neurons in SIH remain unclear. We investigated this using an SIH rat model exposed to electric foot shocks and noise stimulation for 15 days. Analysis of RVLM tissue revealed increased mitochondrial damage, oxidative stress, apoptosis, and dysregulated ferroptosis in SIH rats. RSV microinjection into the RVLM reduced blood pressure, sympathetic vascular tone, and neuronal excitability. Both in vivo and in vitro studies showed that RSV treatment alleviated mitochondrial oxidative stress, apoptosis, and ferroptosis through AMPK activation and subsequent Sirt3 upregulation. These therapeutic effects were blocked by either AMPK inhibition or Sirt3 knockdown. Our findings demonstrate that RSV attenuates SIH by activating the AMPK/Sirt3 pathway, thereby reducing RVLM oxidative stress and cell death.Neuronal hyperexcitability in the rostral ventrolateral medulla (RVLM), driven by oxidative stress, plays a crucial role in stress-induced hypertension (SIH). While resveratrol (RSV) is known for its antioxidant properties, its effects on RVLM neurons in SIH remain unclear. We investigated this using an SIH rat model exposed to electric foot shocks and noise stimulation for 15 days. Analysis of RVLM tissue revealed increased mitochondrial damage, oxidative stress, apoptosis, and dysregulated ferroptosis in SIH rats. RSV microinjection into the RVLM reduced blood pressure, sympathetic vascular tone, and neuronal excitability. Both in vivo and in vitro studies showed that RSV treatment alleviated mitochondrial oxidative stress, apoptosis, and ferroptosis through AMPK activation and subsequent Sirt3 upregulation. These therapeutic effects were blocked by either AMPK inhibition or Sirt3 knockdown. Our findings demonstrate that RSV attenuates SIH by activating the AMPK/Sirt3 pathway, thereby reducing RVLM oxidative stress and cell death. |
| ArticleNumber | 108394 |
| Author | Du, Dong-Shu Li, Yan-Fang Zhang, Hai-Li Liu, Tian-Feng Zhang, Shuai He, Qing Dai, Teng-Teng Tong, Lei Zeng, Qiang-Cheng Wang, Lin-Ping Liu, Hai-Sheng Li, Wen-Zhi Ren, Zhang-Yan Deng, Xin |
| Author_xml | – sequence: 1 givenname: Lin-Ping surname: Wang fullname: Wang, Lin-Ping organization: School of Environmental and Chemical Engineering, Shanghai University, Shanghai, China – sequence: 2 givenname: Tian-Feng surname: Liu fullname: Liu, Tian-Feng organization: School of Environmental and Chemical Engineering, Shanghai University, Shanghai, China – sequence: 3 givenname: Teng-Teng surname: Dai fullname: Dai, Teng-Teng organization: School of Life Sciences, Shanghai University, Shanghai, China – sequence: 4 givenname: Xin surname: Deng fullname: Deng, Xin organization: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Institute of Biomedical Science, Fudan University, Shanghai, China – sequence: 5 givenname: Lei surname: Tong fullname: Tong, Lei organization: School of Life Sciences, Shanghai University, Shanghai, China – sequence: 6 givenname: Qiang-Cheng surname: Zeng fullname: Zeng, Qiang-Cheng organization: College of Life Sciences, Dezhou University, Dezhou, Shandong, China – sequence: 7 givenname: Qing surname: He fullname: He, Qing organization: College of Life Sciences, Dezhou University, Dezhou, Shandong, China – sequence: 8 givenname: Zhang-Yan surname: Ren fullname: Ren, Zhang-Yan organization: School of Life Sciences, Shanghai University, Shanghai, China – sequence: 9 givenname: Hai-Li surname: Zhang fullname: Zhang, Hai-Li organization: College of Agriculture and Bioengineering, Heze University, Heze, Shandong, China – sequence: 10 givenname: Hai-Sheng surname: Liu fullname: Liu, Hai-Sheng organization: College of Agriculture and Bioengineering, Heze University, Heze, Shandong, China – sequence: 11 givenname: Yan-Fang surname: Li fullname: Li, Yan-Fang organization: Department of Preventive Medicine, Heze Medical College, Heze, Shandong, China – sequence: 12 givenname: Wen-Zhi surname: Li fullname: Li, Wen-Zhi email: wenchihlee@sina.com organization: Department of Urology, School of Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China – sequence: 13 givenname: Shuai surname: Zhang fullname: Zhang, Shuai email: szhang@zcmu.edu.cn organization: International Cooperation Laboratory of Molecular Medicine, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China – sequence: 14 givenname: Dong-Shu surname: Du fullname: Du, Dong-Shu email: dsdu@shu.edu.cn organization: School of Environmental and Chemical Engineering, Shanghai University, Shanghai, China |
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| Keywords | DHE Cyt-cyto C ferroptosis mitochondrial oxidative stress apoptosis HR MDA BP Com.C RSNA reactive oxygen species CCK-8 cDNA RVLM DCF qRT-PCR SOD MMP SIH RSV TH AAV CAT NE ROS TEM |
| Language | English |
| License | This is an open access article under the CC BY license. Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
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| Snippet | Neuronal hyperexcitability in the rostral ventrolateral medulla (RVLM), driven by oxidative stress, plays a crucial role in stress-induced hypertension (SIH).... |
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| SubjectTerms | AMP-Activated Protein Kinases - metabolism Animals Antioxidants - pharmacology apoptosis Apoptosis - drug effects ferroptosis Hypertension - drug therapy Hypertension - etiology Hypertension - metabolism Hypertension - pathology Male Medulla Oblongata - drug effects Medulla Oblongata - metabolism Medulla Oblongata - pathology Mitochondria - drug effects Mitochondria - metabolism mitochondrial oxidative stress Neurons - drug effects Neurons - metabolism Neurons - pathology Oxidative Stress - drug effects Rats Rats, Sprague-Dawley reactive oxygen species Resveratrol - pharmacology RVLM Signal Transduction - drug effects Sirtuin 3 - genetics Sirtuin 3 - metabolism Sirtuins |
| Title | Resveratrol reduces RVLM neuron activity via activating the AMPK/Sirt3 pathway in stress-induced hypertension |
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