Inhibition of the Glycolysis Prevents the Cerebral Infarction Progression Through Decreasing the Lactylation Levels of LCP1

Abstract

Cerebral infarction (CI), also known as ischemic stroke, has a high incidence rate and mortality rate. The purpose of this study was to investigate the potential effect and mechanism of Lymphocyte cytosolic protein 1 (LCP1) in the CI progression. The middle cerebral artery occlusion (MCAO) treated rats and oxygen–glucose deprivation/reoxygenation (OGD/R) stimulated PC12 cells were used to establish CI model in vivo and in vitro. The cell proliferation and apoptosis was determined by CCK-8 assay and flow cytometry, respectively. Immunoprecipitation and western blot was performed to test the lactylation levels of LCP1. The cells were treated with cycloheximide to determined the protein stability of LCP1. The glucose uptake and lactate production was determined with commercial kits. The extracellular acidification rate were evaluated by Seahorse. The results showed that LCP1 was upregulated in the MCAO rats and OGD/R stimulated PC12 cells. LCP1 knockdown dramatically decreased the neurological score, infarct volume and the brain water content of MCAO rats. Besides, LCP1 knockdown promoted the cell viability while decreased the apoptosis rate of the OGD/R stimulated PC12 cells. Additionally, the global lactylation and lactylation levels of LCP1 was prominently enhanced in vivo and in vitro in cerebral infarction. 2-DG treatment prominently decreased it. In conclusion, inhibiting the glycolysis decreased the lactylation levels of LCP1 and resulted in the degradation of LCP1, which eventually relieved the CI progression.

Exploring Corneal Neovascularization: An Integrated Approach Using Transcriptomics and Proteomics in an Alkali Burn Mouse Model

“… 22 Recent investigations have also revealed the potential of LCP1 as a therapeutic target for cerebral ischemia–reperfusion injury. 23 In our study, LCP1 exhibited low expression in normal corneas but showed significant upregulation in CNV corneas, possibly because of the low density of immune cells at immune-privileged sites. 24 However, following corneal alkali burn, the influx of immune cells, particularly neutrophils, migrated to the injured area, potentially influencing LCP1 expression.…”

Scopolamine regulates the osteogenic differentiation of human periodontal ligament stem cells through lactylation modification of RUNX2 protein

“…As shown by previous studies, the lactylation modification could enhance protein stability. 18,38 Herein, we performed the half-life profile of RUNX2 and identified that mutation of K176 site shortened the half-life time of RUNX2, indicating that the lactylation of RUNX2 at K176 site affected the stability of RUNX2.…”

MUC20 regulated by extrachromosomal circular DNA attenuates proteasome inhibitor resistance of multiple myeloma by modulating cuproptosis

“…A recent study has reported that hypoxia enhances β-catenin lactylation to improve its stability in colorectal cancer [ 44 ]. Decreased lactylation of lymphocyte cytosolic protein 1 (LCP1) caused by glycolysis inhibition reduces LCP1 stability during cerebral infarction progression [ 45 ]. Moreover, methyltransferase-like 3 (METTL3) lactylation enhances METTL 3 protein stability in intracerebral hemorrhage [ 46 ].…”