α-Lipoic acid protects against hypoxia/reoxygenation-induced injury in human umbilical vein endothelial cells through suppression of apoptosis and autophagy.

Abstract

α-Lipoic acid (ALA) is known as a powerful antioxidant, which has been reported to have protective effects against various cardiovascular diseases. The present study aimed to determine whether ALA pre- or post-treatment induced protective effects against hypoxia/reoxygenation-induced injury via inhibition of apoptosis and autophagy in human umbilical vein endothelial cells (HUVECs). In order to simulate the conditions of hypoxia/reoxygenation, HUVECs were subjected to 4 h of oxygen-glucose deprivation (OGD) followed by 12 h of reoxygenation. For the pre-treatment, ALA was added to the buffer 12 h prior to OGD, whereas for the post-treatment, ALA was added at the initiation of reoxygenation. The results demonstrated that ALA pre- or post-treatment significantly reduced lactate dehydrogenase (LDH) release induced through hypoxia/reoxygenation in HUVECs in a dose-dependent manner; of note, 1 mM ALA pre- or post-treatment exhibited the most potent protective effects. In addition, ALA significantly reduced hypoxia/reoxygenation-induced loss of mitochondrial membrane potential, apoptosis and the expression of cleaved caspase-3 in HUVECs. In the presence of the specific autophagy inhibitor 3-methyladenine, hypoxia/reoxygenation-induced apoptosis was significantly reduced. Furthermore, the formation of autophagosomes, cytosolic microtubule-associated protein 1A/1B-light chain 3 ratio and beclin1 levels significantly increased following hypoxia/reoxygenation injury; however, all of these effects were ameliorated following pre- or post-treatment with ALA. The results of the present study suggested that ALA may provide beneficial protection against hypoxia/reoxygenation-induced injury via attenuation of apoptosis and autophagy in HUVECs.

• Authors: Jingjing Zhang, Houliang Deng, Li Liu, Xiaoxia Liu, Xialin Zuo, Qian Xu, Zhuomin Wu, Xiaobin Peng, Aimin Ji
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 12 Issue 1 Pg. 180-6 (Jul 2015) ISSN: 1791-3004 [Electronic] Greece
• PMID: 25684163 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Apoptosis Regulatory Proteins
• BECN1 protein, human
• Beclin-1
• Membrane Proteins
• Microtubule-Associated Proteins
• 3-methyladenine
• Thioctic Acid
• L-Lactate Dehydrogenase
• Caspase 3
• Glucose
• Adenine
• Oxygen

Topics

• Adenine (analogs & derivatives, pharmacology)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Autophagy (drug effects)
• Beclin-1
• Caspase 3 (genetics, metabolism)
• Cell Hypoxia
• Dose-Response Relationship, Drug
• Gene Expression
• Glucose (deficiency)
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism, ultrastructure)
• Humans
• L-Lactate Dehydrogenase (antagonists & inhibitors, metabolism)
• Membrane Potential, Mitochondrial (drug effects)
• Membrane Proteins (genetics, metabolism)
• Microtubule-Associated Proteins (genetics, metabolism)
• Models, Biological
• Oxygen (pharmacology)
• Phagosomes (drug effects, metabolism, ultrastructure)
• Reperfusion Injury (prevention & control)
• Thioctic Acid (pharmacology)