Protective effects of N,4,5-trimethylthiazol-2-amine hydrochloride on hypoxia-induced β-amyloid production in SH-SY5Y cells
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Although hypoxic/ischemic injury is thought to contribute to the incidence of Alzheimer’s disease (AD), the molecular mechanism that determines the relationship between hypoxiainduced -amyloid (A) generation and development of AD is not yet known. We have now investigated the protective effects of N,4,5-trimethylthiazol-2-amine hydrochloride (KHG26702), a novel thiazole derivative, on oxygen-glucose deprivation (OGD)-reoxygenation (OGD-R)-induced A production in SH-SY5Y human neuroblastoma cells. Pretreatment of these cells with KHG26702 significantly attenuated OGD-R-induced production of reactive oxygen species and elevation of levels of malondialdehyde, prostaglandin E2, interleukin 6 and glutathione, as well as superoxide dismutase activity. KHG26702 also reduced OGD-R-induced expression of the apoptotic protein caspase-3, the apoptosis regulator Bcl-2, and the autophagy protein becn-1. Finally, KHG26702 reduced OGD-R-induced A production and cleavage of amyloid precursor protein, by inhibiting secretase activity and suppressing the autophagic pathway. Although supporting data from in vivo studies are required, our results indicate that KHG26702 may prevent neuronal cell damage from OGD-R-induced toxicity.
Abstract
Although hypoxic/ischemic injury is thought to contribute to the incidence of Alzheimer’s disease (AD), the molecular mechanism that determines the relationship between hypoxiainduced -amyloid (A) generation and development of AD is not yet known. We have now investigated the protective effects of N,4,5-trimethylthiazol-2-amine hydrochloride (KHG26702), a novel thiazole derivative, on oxygen-glucose deprivation (OGD)-reoxygenation (OGD-R)-induced A production in SH-SY5Y human neuroblastoma cells. Pretreatment of these cells with KHG26702 significantly attenuated OGD-R-induced production of reactive oxygen species and elevation of levels of malondialdehyde, prostaglandin E2, interleukin 6 and glutathione, as well as superoxide dismutase activity. KHG26702 also reduced OGD-R-induced expression of the apoptotic protein caspase-3, the apoptosis regulator Bcl-2, and the autophagy protein becn-1. Finally, KHG26702 reduced OGD-R-induced A production and cleavage of amyloid precursor protein, by inhibiting secretase activity and suppressing the autophagic pathway. Although supporting data from in vivo studies are required, our results indicate that KHG26702 may prevent neuronal cell damage from OGD-R-induced toxicity.
참고문헌 (30)
- Taveira M, "Neuroprotective effect of steroid alalkaloids on glutamateinduced toxicity by preserving mitochondrial membrane potential and reducing oxidative stress", J Steroid Biochem Mol Biol, 140, pp.106~115 (2014)
- Nalivaevaa NN, "Effect of hypoxia", ischemia and hypoxic preconditioning, Ann New York Aca Sci, pp.2004, 1035[DOI]
- Pluta R, "Brain ischemia activates β- and γ-secretase cleavage of amyloid precursor protein: significance in sporadic Alzheimer’s disease", Mol Neurobiol, 47, pp.425~434 (2013)
- Salminen A, "Hypoxia", ischemia activate processing of Amyloid precursor protein : impact of vascular dysfunction in the pathogenesis of Alzheimer’s disease, 2017, pp.140, 536~549
- Shiota S, "Chronic intermittent hypoxia", reoxygenation facilitate amyloid-generation in mice, 2013, pp.37, 325~333
- Li L, "Hypoxia increases Aβ generation by altering β-and γ-cleavage of APP", Neurobiol Aging, 30, pp.1091~1098 (2009)
- Li Q, "Salidroside attenuates hypoxia-induced abnormal processing of amyloid precursor protein by decreasing BACE1expression in SH-SY5Y cells", Neurosci Lett, 481, pp.154~158 (2010)
- Margaill I, "Antioxidant strategies in the treatment of stroke", Free Radic Biol Med, 39, pp.429~443 (2005)
- Gould E, "How widespread is adult neurogenesis in mammals?", Nat Rev Neurosci, 8, pp.481~488 (2007)
- -4 pyrimidinyl)acetonitrile) : a c-Jun NH2-terminal protein kinase inhibitor with neuroprotective properties, "J Pharmacol Exp Ther", 2004, 25~32
- Choi MM, "Protective effect of benzothiazole derivative KHG21834 on amyloid beta-induced neurotoxicity in PC12 cells and cortical and mesencephalic neurons", Toxicology, 239, pp.156~166 (2007)
- Miglio G, "Cabergoline protects SH-SY5Y neuronal cells in an in vitro model of ischemia", Eur J Pharmacol, 489, pp.157~165 (2004)
- Fallarini S, "Clovamide and rosmarinic acid induce neuroprotective effects in in vitro models of neuronal death", Br J Pharmacol, 157, pp.1072~1084 (2009)
- Lewen A, "Free radical pathways in CNS injury", J Neurotrauma, 17, pp.871~890 (2000)
- Urabe T, "Accumulation of 4-hydroxynonenal-modified proteins in hippocampal CA1 pyramidal neurons precedes delayed neuronal damage in the gerbil brain", Neuroscience, 100, pp.241~250 (2000)
- Kunwar A, "Curcumin mediates time and concentration dependent regulation of redox homeostasis leading to cytotoxicity in macrophage cells", Eur J Pharmacol, 611, pp.8~16 (2009)
- Katoh S, "Hyperoxia induces the neuronal differentiated phenotype of PC12 cells via a sustained activity of mitogen-activated protein kinase induced by Bcl-2", Biochem J, 338, pp.465~470 (1999)
- Conrad M, "The oxidative stressinducible cystine", glutamate antiporter, system x(c)(-) : cystine supplier and beyond, 2012, pp.42, 231~246
- Le DA, "Caspase activation and neuroprotection in caspase-3-deficient mice after in vivo cerebral ischemia and in vitro oxygen glucose deprivation", Proc Natl Acad Sci U S A, 99, pp.15188~15193 (2002)
- Niwa M, "Caspase activation as an apoptotic evidence in the gerbil hippocampal CA1pyramidal cells following transient forebrain ischemia", Neurosci Lett, 300, pp.103~106 (2001)
- Wang Q, "Neuroprotective mechanisms of curcumin against cerebral ischemiainduced neuronal apoptosis and behavioral deficits", J Neurosci Res, 82, pp.138~148 (2005)
- Zhao H, "Bcl-2overexpression protects against neuron loss within the ischemic margin following experimental stroke and inhibits cytochrome c translocation and caspase-3 activity", J Neurochem, 85, pp.1026~1036 (2003)
- Karch J, "Regulated necrotic cell death : the passive aggressive side of Bax and Bak", Circ Res, 116, pp.1800~1809 (2015)
- Braak H, "Staging of Alzheimerrelated cortical destruction", Eur Neurol, 33, pp.403~408 (1993)
- Suzuki WA, "Functional neuroanatomy of the medial temporal lobe memory system", Cortex, 40, pp.220~222 (2004)
- Banati RB, "Glial expression of the beta-amyloid precursor protein(APP)in global ischemia", J Cereb Blood Flow Metab, 15, pp.647~654 (1995)
- Webster NJ, "Altered processing of amyloid precursor protein in the human neuroblastoma SH-SY5Y by chronic hypoxia", J Neurochem, 83, pp.1262~1271 (2002)
- Mattson MP, "Pathways towards and away from Alzheimer’s disease", Nature, 430, pp.631~639 (2004)
- Müller UC, "Not just amyloid : physiological functions of the amyloid precursor protein family", Nat Rev Neurosci, 18, pp.281~298 (2017)
- Yu WH, "Macroautophagy-a novel Beta-amyloid peptide generating pathway activated in Alzheimer’s disease", J Cell Biol, 171, pp.87~98 (2005)