MAIN METHODS: The effects of BChE on signaling pathways were determined by immunoblotting in a BChE knockout hepatocyte cell line. DiI-LDL probe was used to explore the effect of BChE expression on LDL internalization. Co-immunoprecipitation and LC-MS were used to explore the interacting proteins with BChE. Finally, a hepatocyte-restricted BChE silencing mouse model was established by AAV8-Tbg-shRNA, and the hypercholesterolemia was induced by 65% kcal% high-fat, high-sucrose diet feeding.
MAIN FINDINGS: Here we demonstrate that butyrylcholinesterase (BChE) governs the LDL receptor levels and LDL uptake capacity through the MEK-ERK signaling cascades to promote Ldlr transcription. BChE interacts and co-localizes with PRMT5, a protein methylation modifier controlling the ERK signaling. PRMT5 regulates LDLR-dependent LDL uptake and is a substrate of chaperone-mediated autophagy (CMA). BChE deficiency induces the PRTM5 degradation dependent on CMA activity, possibly through facilitating the HSC70 (Heat shock cognate 71 kDa) recognition of PRMT5. Remarkably, in vivo hepatocyte-restricted BChE silencing reduces plasma cholesterol levels substantially. In contrast, the BChE knockout mice are predisposed to hypercholesterolemia.
SIGNIFICANCE: Taken together, these findings outline a regulatory role for the BChE-PRMT5-ERK-LDLR axis in hepatocyte cholesterol metabolism, and suggest that targeting liver BChE is an effective therapeutic strategy to treat hypercholesterolemia.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1007/s13197-021-05039-y).
METHOD: In order to examine the cultural influence, using a sample of married individuals (N = 7973) from 35 nations, we used multilevel modeling to test whether the positive association between dyadic coping and relationship satisfaction varies across nations and whether gender might moderate the association.
RESULTS: RESULTS reveal that the association between dyadic coping and relationship satisfaction varies between nations. In addition, results show that in some nations the association is higher for men and in other nations it is higher for women.
CONCLUSIONS: Cultural and gender differences across the globe influence how couples' coping behavior affects relationship outcomes. This crucial finding indicates that couple relationship education programs and interventions need to be culturally adapted, as skill trainings such as dyadic coping lead to differential effects on relationship satisfaction based on the culture in which couples live.