title: Protective Effect of Bendavia (SS-31) Against Oxygen/Glucose-Deprivation Stress-Induced Mitochondrial Damage in Human Brain Microvascular Endothelial Cells.
abstract: Mitochondria play a key role in cell survival by perfoming functions such as adenosine tri-phosphate (ATP) synthesis, regulation of apoptotic cell death, calcium storage. Hypoxic conditions induce mitochondrial dysfunction, which leads to endothelial injury in cerebral ischemia. Functional disorders include the following: collapse of mitochondrial membrane potential, reduction of ATP synthesis, and generation of reactive oxygen species (ROS). Bendavia, a novel tetra-peptide, has been reported to restrict the uncoupling of the mitochondrial membrane chain, protect the synthesis of ATP, and inhibit ROS generation. In the present study, we investigated whether bendavia protects mitochondria under hypoxic and starved conditions by using human brain microvascular endothelial cells (HBMVECs). After pre-treatment with bendavia, we exposed HBMVECs to oxygen glucose deprivation (OGD) for 6 h. We then assessed cell viability, the level of caspase-3/7 activity, ROS generation, mitochondrial membrane potential, ATP contents, and the number of mitochondria. Bendavia recovered cell viability and reduced the caspase-3/7 activity induced by OGDinduced damage. Bendavia also recovered mitochondrial functions. These results suggest that bendavia protects mitochondrial function against OGD-induced injury and inhibits apoptosis in HBMVECs. Consequently, our findings indicate that bendavia might become the new therapeutic drug of choice to target mitochondria in case of cerebral ischemia.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Imai
authors.forename: Keisuke
authors.initials: K
authors.lastname: Mishiro
authors.forename: Toshinori
authors.initials: T
authors.lastname: Takagi
authors.forename: Aoi
authors.initials: A
authors.lastname: Isono
authors.forename: Hideko
authors.initials: H
authors.lastname: Nagasawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuruma
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1- 25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D055806:Microvessels; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D009842:Oligopeptides; D017382:Reactive Oxygen Species; C506540:arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide; D005947:Glucose; D010100:Oxygen
keywords: Bendavia; ROS; apoptosis; endothelial cell; hypoxia; mitochondria