Dataset Information

AKG Attenuates Cerebral Ischemia-Reperfusion Injury through c-Fos/IL-10/Stat3 Signaling Pathway.

ABSTRACT: Inflammation is dominant in the pathogenesis of ischemic stroke (IS). Alpha-ketoglutarate (AKG), according to previous studies, has demonstrated a variety of pharmacological effects such as antioxidation and inhibitive inflammation activities. However, whether AKG ameliorates cerebral ischemic injury, as well as the underlying molecular events, is still unclear. Therefore, the effect and underlying mechanisms of AKG on ischemic brain injury should be identified. The study established a cerebral ischemia-reperfusion (I/R) model in mice as well as an oxygen-glucose deprivation/reperfusion (OGD/R) model in SH-SY5Y cells, respectively. It was observed that AKG markedly suppressed infarction volume and neuronal injuries and improved the neurological score in vivo. Moreover, AKG reduced the inflammatory response and lowered the expression of proinflammatory cytokines. In vitro, AKG treatment strongly inhibited OGD/R-induced neuronal injury and the proinflammatory factors. It was also found that the increased SOD and GSH levels, as well as the lower ROS levels, showed that AKG reduced oxidative stress in OGD/R-treated SY-SY5Y cells. Mechanistically, AKG largely promoted IL-10 expression in ischemic brain injury and OGD/R-induced neuronal injury. Furthermore, IL-10 silencing neutralized the protective effect of AKG on inflammation. Notably, it was discovered that AKG could upregulate IL-10 expression by promoting the translocation of c-Fos from the cytoplasm to the nucleus. The results indicated that AKG demonstrated neuroprotection on cerebral ischemia while inhibiting inflammation through c-Fos/IL-10/stat3 pathway.

SUBMITTER: Hua W

PROVIDER: S-EPMC9113869 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

AKG Attenuates Cerebral Ischemia-Reperfusion Injury through c-Fos/IL-10/Stat3 Signaling Pathway.

Hua Weilong W Zhang Xiaoxi X Tang Haishuang H Li Chen C Han Ning N Li He H Ma Hongyu H Liu Pei P Zhou Yihan Y Zhang Hongjian H Zhang Yongxin Y Zhang Lei L Li Zifu Z Shen Hongjian H Xing Pengfei P Yu Longjuan L Zhang Yongwei Y Zhou Yu Y Yang Pengfei P Liu Jianmin J

Oxidative medicine and cellular longevity 20220510

Inflammation is dominant in the pathogenesis of ischemic stroke (IS). Alpha-ketoglutarate (AKG), according to previous studies, has demonstrated a variety of pharmacological effects such as antioxidation and inhibitive inflammation activities. However, whether AKG ameliorates cerebral ischemic injury, as well as the underlying molecular events, is still unclear. Therefore, the effect and underlying mechanisms of AKG on ischemic brain injury should be identified. The study established a cerebral ...[more]

PMID: 35592527

Similar Datasets

Project description:BackgroundMitochondrial dysfunctions play a pivotal role in cerebral ischemia-reperfusion (I/R) injury. Although mitochondrial transplantation has been recently explored for the treatment of cerebral I/R injury, the underlying mechanisms and fate of transplanted mitochondria are still poorly understood.MethodsMitochondrial morphology and function were assessed by fluorescent staining, electron microscopy, JC-1, PCR, mitochondrial stress testing, and metabolomics. Therapeutic effects of mitochondria were evaluated by cell viability, reactive oxygen species (ROS), and apoptosis levels in a cellular hypoxia-reoxygenation model. Rat middle cerebral artery occlusion model was applied to assess the mitochondrial therapy in vivo. Transcriptomics was performed to explore the underlying mechanisms. Mitochondrial fate tracking was implemented by a variety of fluorescent labeling methods.ResultsNeuro-2a (N2a) cell-derived mitochondria had higher mitochondrial membrane potential, more active oxidative respiration capacity, and less mitochondrial DNA copy number. Exogenous mitochondrial transplantation increased cellular viability in an oxygen-dependent manner, decreased ROS and apoptosis levels, improved neurobehavioral deficits, and reduced infarct size. Transcriptomic data showed that the differential gene enrichment pathways are associated with metabolism, especially lipid metabolism. Mitochondrial tracking indicated specific parts of the exogenous mitochondria fused with the mitochondria of the host cell, and others were incorporated into lysosomes. This process occurred at the beginning of internalization and its efficiency is related to intercellular connection.ConclusionsMitochondrial transplantation may attenuate cerebral I/R injury. The mechanism may be related to mitochondrial component separation, altering cellular metabolism, reducing ROS, and apoptosis in an oxygen-dependent manner. The way of isolated mitochondrial transfer into the cell may be related to intercellular connection.

Dataset Information

AKG Attenuates Cerebral Ischemia-Reperfusion Injury through c-Fos/IL-10/Stat3 Signaling Pathway.

Publications

AKG Attenuates Cerebral Ischemia-Reperfusion Injury through c-Fos/IL-10/Stat3 Signaling Pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets