Abstract
Ischemic cerebral stroke is a severe neurodegenerative disease with high mortality. Ischemia and reperfusion injury plays a fundamental role in ischemic cerebral stroke. To date, the strategy for ischemic cerebral stroke treatment is limited. In the present study, we aimed to investigate the effect of kaempferol (KFL), a natural flavonol, on cell injury induced by oxygen and glucose deprivation (OGD) and reoxygenation (OGD-reoxygenation) in PC12 cells. We found that KFL inhibited OGD-induced decrease of cell viability and the increase of lactate dehydrogenase (LDH) release. OGD-induced activation of mitochondrial dysfunction, mitochondrial apoptotic pathway, and apoptosis was inhibited by KFL. KFL also reduced OGD-induced oxidative stress in PC12 cells. P66shc expression and acetylation were increased by OGD and KFL inhibited these changes. Upregulation of P66shc suppressed KFL-induced decrease of apoptosis, the decrease of LDH release, and the increase of cell viability. Furthermore, KFL inhibited OGD-induced decrease of sirtuin 1 (SIRT1) expression and downregulation of SIRT1 blocked KFL-induced decrease of apoptosis, the decrease of LDH release, and the increase of cell viability. In summary, we identified that KFL exhibited a beneficial effect against OGD-induced cytotoxicity in an ischemia/reperfusion injury cell model. The findings suggest that KFL may be a promising choice for the intervention of ischemic stroke and highlighted the SIRT1/P66shc signaling.
Highlights
Ischemic cerebral stroke is a severe neurodegenerative disease that accounts for approximately 70–80% of all cerebrovascular patients with a high risk of disability and mortality [1]. ere are approximately 15 million ischemic stroke patients each year which leads to 5 million deaths annually [2]
Protein expression of cleaved caspase 3, caspase 9, and caspase 7 was substantially increased by oxygen and glucose deprivation (OGD) and this effect was remarkably prohibited by KFL (Figure 2(b))
OGD induced a significant increase of Bax mRNA expression and an obvious decrease of Bcl-2 expression in PC 12 cells (Figures 2(e) and 2(f )). e changes of Bcl-2-associated X (Bax) and B-cell lymphoma 2 (Bcl-2) mRNA expression induced by OGD were notably inhibited by KFL (Figures 2(e) and 2(f )). e results indicated that KFL could attenuate OGD-resulted apoptosis in PC12 cells
Summary
Ischemic cerebral stroke is a severe neurodegenerative disease that accounts for approximately 70–80% of all cerebrovascular patients with a high risk of disability and mortality [1]. ere are approximately 15 million ischemic stroke patients each year which leads to 5 million deaths annually [2]. Ischemic cerebral stroke is a severe neurodegenerative disease that accounts for approximately 70–80% of all cerebrovascular patients with a high risk of disability and mortality [1]. Ere are approximately 15 million ischemic stroke patients each year which leads to 5 million deaths annually [2]. Ischemic stroke is characterized by the sudden neuronal death in the brain due to ischemia and reperfusion injury. Various pathological processes are involved in ischemic cerebral stroke, including oxidative stress, apoptosis, inflammation, neuronal excitotoxicity, and disequilibrium of energy metabolism [3]. A primary concern for reducing ischemic stroke injury is to recover cerebral blood flow and oxygen supply. The resultant cerebral ischemia and reperfusion injury may further aggravate pathological damage in the ischemic district which is potentially rendered irreversible [4]. There are no other novel strategies that have proven to be efficacious and safe for the clinical intervention of ischemic [7]
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