Lactylering van BCAT2-K377 draagt bij aan ernstige pre-eclampsie
Pre-eclampsie wordt gekenmerkt door placentaire hypoxie en oppervlakkige trofoblastinvasie. Dit onderzoek toont aan dat hypoxie-geïnduceerde lactylering van BCAT2 een nieuw mechanisme is dat bijdraagt aan de progressie van ernstige pre-eclampsie.
Abstract (original)
BACKGROUND:Preeclampsia is a pregnancy-specific disorder characterized by placental hypoxia and superficial invasion of trophoblast cells. However, the precise mechanisms by which hypoxia induces lactate and lactylation remain unclear.METHODS:Pan lysine lactylation levels were analyzed in the placentae of 36 patients with severe preeclampsia (sPE) and 36 normotensive pregnancies. A global lactylome analysis was performed, and BCAT2 (branched-chain aminotransferase 2)-K377 was selected for further investigation. The BCAT2-377R mutant was constructed to evaluate the effect on trophoblast migration, invasion, tube formation, and oxidative stress. The impact of the BCAT2-377R mutant on BCAT2 ubiquitination and degradation was further examined using MG132 and cycloheximide supplementation. Co-immunoprecipitation and double-immunofluorescence staining were conducted to identify the lactyltransferase of BCAT2. The specialized antibody was developed to validate BCAT2-K377la (branched-chain ami
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Lees het volledige artikelDOI: 10.1161/HYPERTENSIONAHA.125.25378
