title: 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: Center for Drug Research and Development, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors: Jingjing
authors: J
authors: Zhang
authors: Center for Drug Research and Development, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors: Houliang
authors: H
authors: Deng
authors: Center for Drug Research and Development, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors: Li
authors: L
authors: Liu
authors: Center for Drug Research and Development, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors: Xiaoxia
authors: X
authors: Liu
authors: Institute of Neurosciences, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, P.R. China.
authors: Xialin
authors: X
authors: Zuo
authors: Center for Drug Research and Development, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors: Qian
authors: Q
authors: Xu
authors: Center for Drug Research and Development, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors: Zhuomin
authors: Z
authors: Wu
authors: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors: Xiaobin
authors: X
authors: Peng
authors: Center for Drug Research and Development, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors: Aimin
authors: A
authors: Ji
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D005947:Glucose / Q000172:deficiency; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D010100:Oxygen / Q000494:pharmacology; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015427:Reperfusion Injury / Q000517:prevention & control; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C025946:3-methyladenine; D008063:Thioctic Acid; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; D005947:Glucose; D000225:Adenine; D010100:Oxygen