Folic Acid Deficiency Enhances the Tyr705 and Ser727 Phosphorylation of Mitochondrial STAT3 in In Vivo and In Vitro Mode
- PDF / 2,982,559 Bytes
- 15 Pages / 595.276 x 790.866 pts Page_size
- 105 Downloads / 167 Views
ORIGINAL ARTICLE
Folic Acid Deficiency Enhances the Tyr705 and Ser727 Phosphorylation of Mitochondrial STAT3 in In Vivo and In Vitro Models of Ischemic Stroke Zhiping Dong 1,2 & Xiaoshan Liang 1,3 & Qiang Zhang 3,4 & Suhui Luo 3 & Huan Liu 1,3 & Xuan Wang 1,3 & Na Sai 1,3 & Xumei Zhang 1,3 Received: 8 April 2020 / Revised: 28 September 2020 / Accepted: 30 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Ischemic stroke remains one of the most common causes of death and disability worldwide. The stroke patients with an inadequate intake of folic acid tend to have increased brain injury and poorer prognosis. However, the precise mechanisms underlying the harmful effects of folic acid deficiency (FD) in ischemic stroke is still elusive. Here, we aimed to test the hypothesis that mitochondrial localized STAT3 (mitoSTAT3) expression may be involved in the process of neuronal damage induced by FD in in vivo and in vitro models of ischemic stroke. Our results exhibited that FD increased infarct size and aggravated the damage of mitochondrial ultrastructure in ischemic brains. Meanwhile, FD upregulated the phosphorylation levels of mitoSTAT3 at Tyr705 (Y705) and Ser727 (S727) sites in the rat middle cerebral artery occlusion/reperfusion (MCAO/R) model and oxygen-glucose deprivation followed by reperfusion (OGD/R) N2a cells. Furthermore, the inhibition of JAK2 by AG490 led to a significant decrease in FD-induced phosphorylation of Y705, while S727 phosphorylation was unaffected. Conversely, U0126 and LY294002, which respectively inhibited phosphorylation of ERK1/2 and Akt, partially prevented S727 phosphorylation, but had limited effects on the level of pY705, suggesting that phosphorylation of Y705 and S727 is regulated via independent mechanisms in FD-treated brains. Keywords Folic acid . Ischemic brain . N2a cells . Mitochondrial injury . STAT3 phosphorylation
Introduction Ischemic stroke, the most common type (80%) of stroke, is one of the leading causes of disability and death in adults [1]. There is a * Xumei Zhang [email protected] 1
Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, No 22 Qixiangtai Road, Heping District, Tianjin 300070, China
2
NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin 300134, China
3
Tianjin Key Laboratory of Environment, Nutrition and Public Health, Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin Medical University, Tianjin 300070, China
4
Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China
significant amount of neuronal cell death after a stroke as a result of a lack of essential nutrients and reperfusion. However, few preventive or long-term effective treatment strategies are available
Data Loading...
