Pharmacological Activation of Peroxisome Proliferator-Activated Receptor {Delta} Increases Sphingomyelin Synthase Activity in THP-1 Macrophage-Derived Foam Cell.
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors, which mediate glucose and lipid homeostasis by regulating the expression of a large number of transcription factors. Sphingomyelin synthase (SMS) is a key enzyme in the synthesis of sphingomyelin (SM), and its expression and activity have been reported to be associated with atherosclerosis (AS). Although there have been many functional PPAR and SMS studies on atherosclerosis in recent years, few have investigated the correlation between the activation of PPARδ and the activity of SMS. In his study, macrophage-induced foam cells were utilized to model important pathological changes that occur in AS. The influence of PPARδ agonism by GW501516 on SMS and its product molecule SM were measured. Results indicated that the activation of PPARδ was correlated in a positive manner with the activity of SMS2, and the content of SM was dose dependently increased by GW501516. Together, this study represents the first to suggest that PPARδ activation may be a potential risk of AS through enhancing activity of SMS2.
Hubei University for Nationalities, Enshi, Hubei, 445000, China.
Dongsheng
D
Mou
Department of Neurology, University Hospital of Hubei University for Nationalities, Enshi, Hubei, 445000, China.
Hua
H
Yang
Department of Neurology, University Hospital of Hubei University for Nationalities, Enshi, Hubei, 445000, China.
Changhua
C
Qu
Department of Neurology, University Hospital of Hubei University for Nationalities, Enshi, Hubei, 445000, China.
Juan
J
Chen
Department of Neurology, University Hospital of Hubei University for Nationalities, Enshi, Hubei, 445000, China. zhangchaogui69@163.com.
Chaogui
C
Zhang
D050197:Atherosclerosis / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D005487:Foam Cells / Q000378:metabolism*; D006801:Humans; D008264:Macrophages; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D047494:PPAR delta / Q000819:agonists / Q000378:metabolism*; D013109:Sphingomyelins / Q000096:biosynthesis; D013844:Thiazoles / Q000494:pharmacology; D017855:Transferases (Other Substituted Phosphate Groups) / Q000187:drug effects / Q000378:metabolism*
C425931:GW 501516; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D047494:PPAR delta; D013109:Sphingomyelins; D013844:Thiazoles; C455440:SGMS1 protein, human; D017855:Transferases (Other Substituted Phosphate Groups); C070186:phosphatidylcholine-ceramide phosphocholine transferase
GW501516; atherosclerosis; peroxisome proliferator-activated receptors; sphingomyelin synthase