Xiaoyin He, Zhenzhen Wang, Qingbo Ge, Shuyu Sun, Ruru Li, Baoping Wang
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引用次数: 0
Abstract
Ischemic stroke remains a major cause of disability and mortality. Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy is involved in cerebral ischemic injury. Additionally, lactylation regulates the progression of ischemia injury. This study aimed to investigate the impact of NCOA4 on ferritinophagy and glycolysis of hippocampal neuron cells and its lactylation modification. Middle cerebral artery occlusion (MCAO) mouse and oxygen-glucose deprivation (OGD)-treated HT22 cell models were generated. Ferritinophagy was evaluated via detecting ferrous iron (Fe 2+ ), glutathione, malondialdehyde, and protein levels. Glycolysis was assessed by examining the glucose consumption, lactate production, and extracellular acidification rate. The lactylation was evaluated using immunoprecipitation and immunoblotting. Brain injury in vivo was analyzed by measuring brain infarct and neurological function. The results showed that NCOA4 expression was increased in the blood of patients with acute ischemia stroke, the peri-infarct region of the brain in MCAO mice (increased percentage: 142.11%) and OGD-treated cells (increased percentage: 114.70%). Knockdown of NCOA4 inhibited ferritinophagy and glycolysis of HT22 cells induced by OGD. Moreover, OGD promoted the lactylation of NCOA4 at lysine (K)450 sites, which enhanced NCOA4 protein stability. Additionally, interfering with NCOA4 attenuated brain infarction and neurological dysfunction in MCAO mice. Lactylation of NCOA4 at K450 sites promotes ferritinophagy and glycolysis of hippocampal neuron cells, thereby accelerating cerebral ischemic injury. These findings suggest a novel pathogenesis of ischemic stroke.
期刊介绍:
NeuroReport is a channel for rapid communication of new findings in neuroscience. It is a forum for the publication of short but complete reports of important studies that require very fast publication. Papers are accepted on the basis of the novelty of their finding, on their significance for neuroscience and on a clear need for rapid publication. Preliminary communications are not suitable for the Journal. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.
The core interest of the Journal is on studies that cast light on how the brain (and the whole of the nervous system) works.
We aim to give authors a decision on their submission within 2-5 weeks, and all accepted articles appear in the next issue to press.