Sphingomyelin synthase overexpression increases cholesterol accumulation and decreases cholesterol secretion in liver cells

Abstract

BackgroundStudies have shown that plasma high density lipoprotein cholesterol levels are negatively correlated with the development of atherosclerosis, whereas epidemiological studies have also shown that plasma sphingomyelin level is an independent risk factor for atherosclerosis.MethodsTo evaluate the relationship between cellular sphingomyelin level and cholesterol metabolism, we created two cell lines that overexpressed sphingomyelin synthase 1 or 2 (SMS1 or SMS2), using the Tet-off expression system.ResultsWe found that SMS1 or SMS2 overexpression in Huh7 cells, a human hepatoma cell line, significantly increased the levels of intracellular sphingomyelin, cholesterol, and apolipoprotein A-I and decreased levels of apolipoprotein A-I and cholesterol in the cell culture medium, implying a defect in both processes.ConclusionsOur findings indicate that the manipulation of sphingomyelin synthase activity could influence the metabolism of sphingomyelin, cholesterol and apolipoprotein A-I.

Circular RNA of the human sphingomyelin synthase 1 gene: Multiple splice variants, evolutionary conservatism and expression in different tissues

“…[1][2][3][4] Previously, we studied the structure of the human SGMS1 gene and characterized transcripts of this gene that are potentially able to direct protein synthesis. We established that the transcriptional diversity of the SGMS1 gene is provided by the presence of alternative promoters, alternative polyadenylation and exon splicing.…”

Pharmacological Activation of Peroxisome Proliferator-Activated Receptor {Delta} Increases Sphingomyelin Synthase Activity in THP-1 Macrophage-Derived Foam Cell

“…Adenovirus-mediated SMS1 and SMS2 overexpressions lead to increased liver SMS activity, which contributes to the increased plasma SM levels [10]. SMS overexpression-mediated SM increases paralleled the cholesterol content changes in a human hepatoma cell line [47]. Conversely, SMS2-deficient mice showed a significant decrease in plasma SM levels either on a chow diet or on a high-fat diet [26].…”

“…Increased sphingomyelin content impaired (LCAT)-mediated maturation and is attributed to HDL deficiency. Further, recent studies have found that augmented expression of SMS increased the levels of intracellular SM, cholesterol, and apolipoprotein A-I within Huh7 cells [47]. Overexpressions of both SMS1 and SMS2 increased cellular SM and DAG levels and induced TNF-α-mediated CHO cell apoptosis [9].…”

Effects of sepsis on the metabolism of sphingomyelin and cholesterol in mice with liver dysfunction

“…Furthermore, patients with Niemann-Pick disease cannot hydrolyze SM due to defective SMase, resulting in the accumulation of SM and cholesterol in the liver and the nervous system (33). Additionally, because ABCA1 is a transmembrane protein that is located in or near the lipid raft, some researchers have implied that the enhancement of SM and cholesterol may also increase the ABCA1 expression in cells (32).…”