title: Reduction in Autophagy by (-)-Epigallocatechin-3-Gallate (EGCG): a Potential Mechanism of Prevention of Mitochondrial Dysfunction After Subarachnoid Hemorrhage.
abstract: Mitochondrial dysfunction and subsequent autophagy, which are common features in central nervous system (CNS) disorders, were found to contribute to neuronal cell injury after subarachnoid hemorrhage (SAH). (-)-Epigallocatechin-3-gallate (EGCG), the main biological active of tea catechin, is well known for its beneficial effects in the treatment of CNS diseases. Here, the ability of EGCG to rescue cellular injury and mitochondrial function following the improvement of autophagic flux after SAH was investigated. As expected, EGCG-protected mitochondrial function depended on the inhibition of cytosolic Ca2+concentration ([Ca2+]i) influx via voltage-gated calcium channels (VGCCs) and, consequently, mitochondrial Ca2+concentration ([Ca2+]m) overload via mitochondrial Ca2+uniporter (MCU). The attenuated [Ca2+]iand [Ca2+]mlevels observed in the EGCG-treated group likely lessened oxyhemoglobin (OxyHb)-induced mitochondrial dysfunction, including mitochondrial membrane potential depolarization, mitochondrial membrane permeability transition pore (mPTP) opening, reactive oxygen species (ROS), and cytochrosome c (cyt c) releasing. Subsequently, EGCG can restore the disrupted autophagy flux after SAH both at the initiation and formation stages by regulating Atg5, LC3B, and Becn-1 (Beclin-1) mRNA expressions. Thus, precondition EGCG resulted in autophagosomes and more autolysosomes compared with SAH group. As a result, EGCG pre-treatment increased the neurological score and decreased cell death. This study suggested that the mitochondrial dysfunction and abnormal autophagy flux synergistically contribute to SAH pathogenesis. Thus, EGCG can be regarded as a new pharmacological agent that targets both mitochondria and altered autophagy in SAH therapy.
authors.affiliation: College of Life Sciences, Henan Normal University, Xinxiang, Henan, 453007, China. yingch0816@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, 453100, China.
authors.forename: Liyong
authors.initials: L
authors.lastname: Huang
authors.affiliation: College of Life Science and Biotechnology, Xinxiang Medical University, Xinxiang, Henan, 453003, China.
authors.forename: Huiyong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, 453100, China.
authors.forename: Xiling
authors.initials: X
authors.lastname: Diao
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, 453100, China.
authors.forename: Shuyang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, 453100, China.
authors.forename: Wenke
authors.initials: W
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016716:PC12 Cells; D051381:Rats; D013345:Subarachnoid Hemorrhage / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*
chemical_list: D018696:Neuroprotective Agents; D002392:Catechin; C045651:epigallocatechin gallate
keywords: Autophagy; Ca2+; EGCG; Mitochondrial dysfunction; Subarachnoid hemorrhage