Age-related alteration in hepatic acyl-CoA: cholesterol acyltransferase and its relation to LDL receptor and MAPK.
The aim of this study was to evaluate changes in the regulation of lipid metabolism and mitogen-activated protein kinases (MAPK) in the liver of C57BL/6 mice as they age. This was done by assessing the status of total cholesterol content and its enzyme, acyl-CoA: cholesterol acyltransferase (ACAT), in liver microsomal preparations and the low-density lipoprotein receptor (LDLr) mRNA expression in the livers of 4-24-month-old C57B/6 mice, without exogenous cholesterol feeding. With aging, there was an increase in cholesterol content and ACAT activity in liver microsomes. Northern blot analysis and real-time quantitative polymerase chain reaction data showed that ACAT-2 mRNA increased with age as well. LDLr expression decreased significantly in an age-dependent manner. In addition, we studied the basal and activated forms of MAPK, e.g. extracellular regulatory kinase (ERK-1/2), c-jun NH2-terminal kinase (JNK-1/2) and p38 MAPK. During aging, there was a considerable decrease in phosphorylated ERK-1/2 level while JNK-1/2 and p38 MAPK levels increased with age. Our studies showed an altered LDLr expression and altered phosphorylated MAPK in the liver of C57BL/6 mice during aging. These alterations might contribute to the development of atherosclerosis, hypercholesterolemia and other cholesterol-related conditions.
Bose
Chhanda
C
Donald W. Reynolds Department of Geriatrics, University of Arkansas for Medical Sciences and Medical Research, Central Arkansas Veterans Healthcare System, Little Rock, 72205, USA.
Bhuvaneswaran
Chidambaram
C
Udupa
Kodetthoor B
KB
D000375:Aging / Q000378:metabolism*; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011973:Receptors, LDL / Q000096:biosynthesis*; D002785:Sterol O-Acyltransferase / Q000378:metabolism*
D011973:Receptors, LDL; D002785:Sterol O-Acyltransferase; D020928:Mitogen-Activated Protein Kinases