title: Cytoprotection against Hypoxic and/or MPP⁺ Injury: Effect of δ-Opioid Receptor Activation on Caspase 3.
abstract: The pathological changes of Parkinson's disease (PD) are, at least partially, associated with the dysregulation of PTEN-induced putative kinase 1 (PINK1) and caspase 3. Since hypoxic and neurotoxic insults are underlying causes of PD, and since δ-opioid receptor (DOR) is neuroprotective against hypoxic/ischemic insults, we sought to determine whether DOR activation could protect the cells from damage induced by hypoxia and/or MPP⁺ by regulating PINK1 and caspase 3 expressions. We exposed PC12 cells to either severe hypoxia (0.5%-1% O₂) for 24-48 h or to MPP⁺ at different concentrations (0.5, 1, 2 mM) and then detected the levels of PINK1 and cleaved caspase 3. Both hypoxia and MPP⁺ reduced cell viability, progressively suppressed the expression of PINK1 and increased the cleaved caspase 3. DOR activation using UFP-512, effectively protected the cells from hypoxia and/or MPP⁺ induced injury, reversed the reduction in PINK1 protein and significantly attenuated the increase in the cleaved caspase 3. On the other hand, the application of DOR antagonist, naltrindole, greatly decreased cell viability and increased cleaved caspase 3. These findings suggest that DOR is cytoprotective against both hypoxia and MPP⁺ through the regulation of PINK1 and caspase 3 pathways.
authors: Modern Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou 213000, Jiangsu, China. 13685262339@163.com.
authors: Yuan
authors: Y
authors: Xu
authors: Modern Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou 213000, Jiangsu, China. danielzhif@163.com.
authors: Feng
authors: F
authors: Zhi
authors: Modern Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou 213000, Jiangsu, China. naiyuanshao@126.com.
authors: Naiyuan
authors: N
authors: Shao
authors: Modern Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou 213000, Jiangsu, China. wangrong1949@163.com.
authors: Rong
authors: R
authors: Wang
authors: Modern Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou 213000, Jiangsu, China. bigyang@vip.sina.com.
authors: Yilin
authors: Y
authors: Yang
authors: Department of Neurosurgery, The University of Texas McGovern Medical School, Houston, TX 77030, USA. Y55738088@gmail.com.
authors: Ying
authors: Y
authors: Xia
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism*; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016716:PC12 Cells; D010300:Parkinson Disease / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D015655:1-Methyl-4-phenylpyridinium; D053148:Caspase 3; D011494:Protein Kinases; D017465:Receptors, Opioid, delta; D000099202:PTEN-Induced Putative Kinase
keywords: MPP+; PINK1; Parkinson’s disease; caspase 3; cytoprotection; hypoxia; δ-opioid receptor