Inhibiting aberrant p53-PUMA feedback loop activation attenuates ischaemia reperfusion-induced neuroapoptosis and neuroinflammation in rats by downregulating caspase 3 and the NF-κB cytokine pathway.

Journal of Neuroinflammation
Xiao-Qian LiHong Ma

Abstract

Ischaemia reperfusion (IR) induces multiple pathophysiological changes. In addition to its classical role in regulating tumourigenesis, the feedback loop formed by p53 and its driven target p53-upregulated modulator of apoptosis (PUMA) was recently demonstrated to be the common node tightly controlling various cellular responses during myocardial IR. However, the roles of the p53-PUMA feedback loop in the spinal cord remain unclear. This study aimed to elucidate the roles of p53-PUMA feedback interactions in the spinal cord after IR, specifically investigating their regulation of caspase 3-mediated apoptosis and nuclear factor (NF)-κB-mediated cytokine release. SD rats subjected to 12 min of aortic arch occlusion served as IR models. Neurological assessment as well as p53 and PUMA mRNA and protein expression analyses were performed at 12-h intervals during a 48-h reperfusion period. The cellular distributions of p53 and PUMA were determined via double immunofluorescence staining. The effects of the p53-PUMA feedback loop on modulating hind-limb function; the number of TUNEL-positive cells; and protein levels of caspase 3, NF-κB and cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α, were evaluated by intrathecal t...Continue Reading

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Citations

Aug 30, 2020·Journal of Neuroinflammation·Mengya JiaoHui Yin
Nov 24, 2020·Frontiers in Cell and Developmental Biology·Wei ZhouQifa Ye
Jun 7, 2021·Journal of Biochemical and Molecular Toxicology·Lian ZengHuiyu Luo
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mengya JiaoHui Yin
Jun 19, 2021·Molecular Therapy. Methods & Clinical Development·Xiuqing ZhangXiaoliu Dong

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Methods Mentioned

BETA
electrophoresis
confocal microscopy
immunoprecipitation
pull-down
nuclear translocation

Software Mentioned

Quantity One
SPSS

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