Nesfatin-1 antagonized rotenone-induced neurotoxicity in MES23.5 dopaminergic cells.
Nesfatin-1 is a recently identified brain-gut peptide involved in feeding and energy homeostasis. Recently, it has been proved that nesfatin-1 could exert its neuroprotective effect against subarachnoid hemorrhage-induced injury via its anti-apoptotic and anti-inflammatory properties. However, whether it has neuroprotective effect on dopamine neurons is largely unknown. In the present study, we investigated the neuroprotective effect of nesfatin-1 on rotenone-treated MES23.5 dopaminergic cells and illustrated the underlying mechanisms. Our results showed that nesfatin-1 pretreatment could significantly attenuate rotenone-induced cell loss. Further studies showed that the neuroprotective effect of nesfatin-1 against rotenone was mediated by reversing rotenone-induced mitochondrial dysfunction. Nesfatin-1 could rescue rotenone-induced mitochondrial transmembrane potential collapse and restore the function of mitochondrial respiratory chain complex I. In addition, rotenone-induced release of cytochrome C from mitochondria, ROS production and the subsequent caspase-3 activation were also attenuated by nesfatin-1 pretreatment. Our data suggested that nesfatin-1 exerted its neuroprotective effect on dopaminergic cells against rotenone by ameliorating mitochondrial dysfunction and its anti-apoptotic property. This suggested that nesfatin-1 had the potential to be considered as an aid for prevention of Parkinson's disease.
Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Medical College of Qingdao University, Qingdao, 266071, China.
Zhen
Z
Tan
Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Medical College of Qingdao University, Qingdao, 266071, China.
Huamin
H
Xu
Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Medical College of Qingdao University, Qingdao, 266071, China.
Xiaoli
X
Shen
Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Medical College of Qingdao University, Qingdao, 266071, China. Electronic address: jhkyk@163.com.
Hong
H
Jiang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000008:administration & dosage / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006822:Hybrid Cells / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism; D000080866:Nucleobindins; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C000630650:NUCB2 protein, human; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C000630651:Nucb1 protein, mouse; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D017382:Reactive Oxygen Species; D012402:Rotenone; D004298:Dopamine
Apoptosis; Dopamine neuron; Nesfatin-1; Parkinson's disease; Rotenone