Protective effect of hydrogen against ischemia-reperfusion induced spinal nerve cell apoptosis

Background: This study aims to explore the protective effect of hydrogen against oxygen-glucose-serum deprivation/restoration (OGSD/R)-induced PC12 cell apoptosis in vitro and the possible underlying mechanism. Methods: A normal control (NC) group was set where PC12 cells were cultured normal, while a positive control (PC) group, where PC12 cells were exposed to OGSD 12h/R1h without intervention, and a hydrogen intervention (HI) group, where PC12 cells were exposed to OGSD 12h/R1h plus HI, were conducted at the same time. At OGSD 12h/R 1h, cells were DAPI stained to detect viability and changes in the expression of apoptosis-associated proteins caspase-3, caspase-12 and CHOP/GADD153, and the endoplasmic reticulum-related signaling pathway protein PERK-eIF2α-ATF4. At the same time, the effect of HI was observed. Results: The result revealed that compared with NC group, cell apoptosis was more severe and cell viability was reduced significantly in PC group, while cell apoptosis was ameliorated and cell viability was increased significantly in HI as compared with PC group. In addition, the content of caspase-3 and caspase-12 in HI group was decreased significantly as compared with that in PC group. During this process, the endoplasmic reticulum-related signaling pathway protein PERK-eIF2α-ATF4 was activated. In HI group, the expression of this protein was decreased and cell viability was increased significantly as compared with those in PC group. Conclusions: Hydrogen was able to inhibit OGSD/R-induced PC12 cell apoptosis and exert a protective effect against ischemia-repurfusion injury (IRI) to nerve cells, probably through inhibiting the endoplasmic reticulum-related signaling pathway protein.

[1]  M. Nemethova,et al.  Neuroprotection mediated by remote preconditioning is associated with a decrease in systemic oxidative stress and changes in brain and blood glutamate concentration , 2019, Neurochemistry International.

[2]  H. Yao,et al.  Intake of Molecular Hydrogen in Drinking Water Increases Membrane Transporters, p-Glycoprotein, and Multidrug Resistance-Associated Protein 2 without Affecting Xenobiotic-Metabolizing Enzymes in Rat Liver , 2019, Molecules.

[3]  Xiao‐Kang Li,et al.  Hydrogen inhalation protects hypoxic–ischemic brain damage by attenuating inflammation and apoptosis in neonatal rats , 2019, Experimental biology and medicine.

[4]  Jin Zhang,et al.  Recent Advances in Studies of Molecular Hydrogen against Sepsis , 2019, International journal of biological sciences.

[5]  D. Rutkowski Liver function and dysfunction – a unique window into the physiological reach of ER stress and the unfolded protein response , 2019, The FEBS journal.

[6]  Feng Xu,et al.  Estrogen and propofol combination therapy inhibits endoplasmic reticulum stress and remarkably attenuates cerebral ischemia-reperfusion injury and OGD injury in hippocampus. , 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[7]  Yong Huang,et al.  Porcine parvovirus infection impairs progesterone production in luteal cells through mitogen-activated protein kinases, p53, and mitochondria-mediated apoptosis† , 2018, Biology of Reproduction.

[8]  Haiyan Li,et al.  TNF‐&agr; increases Staphylococcus aureus‐induced death of human alveolar epithelial cell line A549 associated with RIP3‐mediated necroptosis , 2018, Life sciences.

[9]  Boxu Ren,et al.  Transcription Factor C/EBP Homologous Protein in Health and Diseases , 2017, Front. Immunol..

[10]  Yuanyuan Zhang,et al.  Inhibition of Starvation-Triggered Endoplasmic Reticulum Stress, Autophagy, and Apoptosis in ARPE-19 Cells by Taurine through Modulating the Expression of Calpain-1 and Calpain-2 , 2017, International journal of molecular sciences.

[11]  M. Bhuiyan,et al.  Sigmar1 regulates endoplasmic reticulum stress-induced C/EBP-homologous protein expression in cardiomyocytes , 2017, Bioscience reports.

[12]  Meixiang Xiang,et al.  Involvement of Endoplasmic Reticulum Stress–Mediated C/EBP Homologous Protein Activation in Coxsackievirus B3–Induced Acute Viral Myocarditis , 2015, Circulation. Heart failure.

[13]  W. Dorsett-Martin,et al.  Hepatocyte autophagy is linked to C/EBP-homologous protein, Bcl2-interacting mediator of cell death, and BH3-interacting domain death agonist gene expression. , 2015, The Journal of surgical research.

[14]  W. Xu,et al.  Effects of three hydrogen-rich liquids on hemorrhagic shock in rats. , 2015, The Journal of surgical research.

[15]  S. Ohta Molecular hydrogen as a novel antioxidant: overview of the advantages of hydrogen for medical applications. , 2015, Methods in enzymology.

[16]  M. Duan,et al.  Hydrogen-rich saline attenuates neuronal ischemia--reperfusion injury by protecting mitochondrial function in rats. , 2014, The Journal of surgical research.

[17]  C. Suo,et al.  [Effects of hydrogen-rich saline on endoplasmic reticulum stress during myocardial ischemia-reperfusion in rats]. , 2014, Zhonghua yi xue za zhi.

[18]  E. Isenovic,et al.  Link Between Oxidative Stress and Acute Brain Ischemia , 2014, Angiology.

[19]  Le Yang,et al.  Endoplasmic reticulum stress and C/EBP homologous protein-induced Bax translocation are involved in angiotensin II-induced apoptosis in cultured neonatal rat cardiomyocytes , 2012, Experimental biology and medicine.

[20]  M. Seeliger,et al.  Pharmacological Modulation of the Retinal Unfolded Protein Response in Bardet-Biedl Syndrome Reduces Apoptosis and Preserves Light Detection Ability* , 2012, The Journal of Biological Chemistry.

[21]  I. Komuro,et al.  Ablation of C/EBP Homologous Protein Attenuates Endoplasmic Reticulum–Mediated Apoptosis and Cardiac Dysfunction Induced by Pressure Overload , 2010, Circulation.

[22]  John H. Zhang,et al.  Hydrogen therapy reduces apoptosis in neonatal hypoxia–ischemia rat model , 2008, Neuroscience Letters.

[23]  M. Bullock,et al.  Validation of brain extracellular glycerol as an indicator of cellular membrane damage due to free radical activity after traumatic brain injury. , 2008, Journal of neurotrauma.

[24]  P. Dash,et al.  Acute ethanol intake attenuates inflammatory cytokines after brain injury in rats: a possible role for corticosterone. , 2002, Journal of neurotrauma.