2. Academic Validation
  3. Deficiency of ROS-Activated TRPM2 Channel Protects Neurons from Cerebral Ischemia-Reperfusion Injury through Upregulating Autophagy

Deficiency of ROS-Activated TRPM2 Channel Protects Neurons from Cerebral Ischemia-Reperfusion Injury through Upregulating Autophagy

  • Oxid Med Cell Longev. 2021 Jul 27;2021:7356266. doi: 10.1155/2021/7356266.
Xupang Hu  # 1,  Lijuan Wu  # 1 2,  Xingyu Liu  # 1,  Yi Zhang 1,  Min Xu 1,  Qiuyuan Fang 1,  Lin Lu 3,  Jianguo Niu 4,  Tarek Mohamed Abd El-Aziz 5 6,  Lin-Hua Jiang 7,  Fangfang Li 1,  Wei Yang 1
Affiliations

Affiliations

  • 1 Department of Biophysics, and Department of Neurosurgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
  • 2 School of Medicine, Taizhou University, Taizhou 318000, China.
  • 3 School of Medicine, Zhejiang University City College, Hangzhou 310015, China.
  • 4 Ningxia Key Laboratory of Craniocerebral Diseases, Ningxia Medical University, Yinchuan 750004, China.
  • 5 Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
  • 6 Zoology Department, Faculty of Science, Minia University, El-Minia 61519, Egypt.
  • 7 School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK.
  • # Contributed equally.
PMID: 34367466 DOI: 10.1155/2021/7356266
Abstract

Cerebral ischemia-reperfusion (I-R) transiently increased Autophagy by producing excessively Reactive Oxygen Species (ROS); on the Other hand, activated Autophagy would remove ROS-damaged mitochondria and proteins, which led to cell survival. However, the regulation mechanism of Autophagy activity during cerebral I-R is still unclear. In this study, we found that deficiency of the TRPM2 channel which is a ROS sensor significantly decreased I-R-induced neuronal damage. I-R transiently increased Autophagy activity both in vitro and in vivo. More importantly, TRPM2 deficiency decreased I-R-induced neurological deficit score and infarct volume. Interestingly, our results indicated that TRPM2 deficiency could further activate AMPK rather than Beclin1 activity, suggesting that TRPM2 inhibits Autophagy by regulating the AMPK/mTOR pathway in I-R. In conclusion, our study reveals that ROS-activated TRPM2 inhibits Autophagy by downregulating the AMPK/mTOR pathway, which results in neuronal death induced by cerebral I-R, further supporting that TRPM2 might be a potential drug target for cerebral ischemic injury therapy.

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