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Protective Effect of Bendavia (SS-31) Against Oxygen/Glucose-Deprivation Stress-Induced Mitochondrial Damage in Human Brain Microvascular Endothelial Cells

[ Vol. 14 , Issue. 1 ]

Author(s):

Takahiko Imai, Keisuke Mishiro, Toshinori Takagi, Aoi Isono, Hideko Nagasawa, Kazuhiro Tsuruma, Masamitsu Shimazawa and Hideaki Hara   Pages 53 - 59 ( 7 )

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.

Keywords:

Bendavia, mitochondria, apoptosis, endothelial cell, ROS, hypoxia.

Affiliation:

Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1- 25-4 Daigaku-nishi, Gifu 501-1196



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