Cholesterol-enriched membrane microdomains ...
Type de document :
Article dans une revue scientifique
DOI :
PMID :
URL permanente :
Titre :
Cholesterol-enriched membrane microdomains are needed for insulin signaling and proliferation in hepatic cells.
Auteur(s) :
Fonseca Matheus De, Castro [Auteur]
Franca, Andressa [Auteur]
Florentino Rodrigo, Machado [Auteur]
Fonseca Roberta, Cristelli [Auteur]
Melo Antonio, Carlos [Auteur]
Vidigal Paula Teixeira, Vieira [Auteur]
Oliveira Andre, G [Auteur]
Dubuquoy, Laurent [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Nathanson Michael, H [Auteur]
Leite M, Fatima [Auteur]
Franca, Andressa [Auteur]
Florentino Rodrigo, Machado [Auteur]
Fonseca Roberta, Cristelli [Auteur]
Melo Antonio, Carlos [Auteur]
Vidigal Paula Teixeira, Vieira [Auteur]
Oliveira Andre, G [Auteur]
Dubuquoy, Laurent [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Nathanson Michael, H [Auteur]
Leite M, Fatima [Auteur]
Titre de la revue :
American journal of physiology. Gastrointestinal and liver physiology
Nom court de la revue :
Am. J. Physiol. Gastrointest. Liver Physiol.
Numéro :
315
Pagination :
G80-G94
Date de publication :
2018-07
ISSN :
1522-1547
Mot(s)-clé(s) :
calcium signaling
insulin signaling
hepatocytes
liver regeneration
lipid rafts
insulin signaling
hepatocytes
liver regeneration
lipid rafts
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Hepatocyte proliferation during liver regeneration is a well-coordinated process regulated by the activation of several growth factor receptors, including the insulin receptor (IR). The IR can be localized in part to ...
Lire la suite >Hepatocyte proliferation during liver regeneration is a well-coordinated process regulated by the activation of several growth factor receptors, including the insulin receptor (IR). The IR can be localized in part to cholesterol-enriched membrane microdomains, but the role of such domains in insulin-mediated events in hepatocytes is not known. We investigated whether partitioning of IRs into cholesterol-enriched membrane rafts is important for the mitogenic effects of insulin in the hepatic cells. IR and lipid rafts were labeled in HepG2 cells and primary rat hepatocytes. Membrane cholesterol was depleted in vitro with metyl-β-cyclodextrin (MβCD) and in vivo with lovastatin. Insulin-induced calcium (Ca2+) signals studies were examined in HepG2 cells and in freshly isolated rat hepatocytes as well as in whole liver in vivo by intravital confocal imaging. Liver regeneration was studied by 70% partial hepatectomy (PH), and hepatocyte proliferation was assessed by PCNA staining. A subpopulation of IR was found in membrane microdomains enriched in cholesterol. Depletion of cholesterol from plasma membrane resulted in redistribution of the IR along the cells, which was associated with impaired insulin-induced nuclear Ca2+ signals, a signaling event that regulates hepatocyte proliferation. Cholesterol depletion also led to ERK1/2 hyper-phosphorylation. Lovastatin administration to rats decreased hepatic cholesterol content, disrupted lipid rafts and decreased insulin-induced Ca2+ signaling in hepatocytes, and delayed liver regeneration after PH. Therefore, membrane cholesterol content and lipid rafts integrity showed to be important for the proliferative effects of insulin in hepatic cells.Lire moins >
Lire la suite >Hepatocyte proliferation during liver regeneration is a well-coordinated process regulated by the activation of several growth factor receptors, including the insulin receptor (IR). The IR can be localized in part to cholesterol-enriched membrane microdomains, but the role of such domains in insulin-mediated events in hepatocytes is not known. We investigated whether partitioning of IRs into cholesterol-enriched membrane rafts is important for the mitogenic effects of insulin in the hepatic cells. IR and lipid rafts were labeled in HepG2 cells and primary rat hepatocytes. Membrane cholesterol was depleted in vitro with metyl-β-cyclodextrin (MβCD) and in vivo with lovastatin. Insulin-induced calcium (Ca2+) signals studies were examined in HepG2 cells and in freshly isolated rat hepatocytes as well as in whole liver in vivo by intravital confocal imaging. Liver regeneration was studied by 70% partial hepatectomy (PH), and hepatocyte proliferation was assessed by PCNA staining. A subpopulation of IR was found in membrane microdomains enriched in cholesterol. Depletion of cholesterol from plasma membrane resulted in redistribution of the IR along the cells, which was associated with impaired insulin-induced nuclear Ca2+ signals, a signaling event that regulates hepatocyte proliferation. Cholesterol depletion also led to ERK1/2 hyper-phosphorylation. Lovastatin administration to rats decreased hepatic cholesterol content, disrupted lipid rafts and decreased insulin-induced Ca2+ signaling in hepatocytes, and delayed liver regeneration after PH. Therefore, membrane cholesterol content and lipid rafts integrity showed to be important for the proliferative effects of insulin in hepatic cells.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Inserm
Université de Lille
CHU Lille
Université de Lille
CHU Lille
Équipe(s) de recherche :
Inflammatory digestive disease : pathophysiology and therapeutic targets developement
Date de dépôt :
2019-03-01T14:46:26Z
2023-12-01T13:35:30Z
2023-12-01T13:35:30Z