H2 S inhibits apo(a) expression and secretion through PKCα/FXR and Akt/HNF4α pathways in HepG2 cells.
Lipoprotein(a) [Lp(a)] is a strong genetic risk factor for coronary heart diseases. However, the metabolism of this protein remains poorly understood. Efficient and specific drugs that can decrease high plasma levels of Lp(a) have not been developed yet. Hydrogen sulfide (H2 S), a member of the gas transmitter family, performs important biological actions, including protection against cardiovascular diseases and maintenance of the lipid metabolism equilibrium in hepatocytes and adipocytes. In this study, we investigated the possible molecular mechanism of H2 S that influences apolipoprotein(a) [apo(a)] biosynthesis. We also determined the effects of H2 S on apo(a) expression and secretion in HepG2 cells as well as the underlying mechanisms. Results showed that H2 S significantly inhibited the expression and secretion levels of apo(a). These effects were attenuated by the PKCα inhibitor and FXR siRNA. H2 S also reduced HNF4α expression and enhanced FXR expression. The Akt inhibitor partially reversed H2 S-induced inhibition of apo(a) and HNF4α expression and apo(a) secretion. This study reveals that H2 S suppressed apo(a) expression and secretion via the PKCα-FXR and PI3K/Akt-HNF4α pathways.
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan, 421001, PR China.
Kai
K
Qu
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan, 421001, PR China.
Ya-Mi
YM
Liu
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan, 421001, PR China.
Xing-Lan
XL
He
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan, 421001, PR China.
Hai
H
Zhang
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan, 421001, PR China.|The Second Hospital Affiliated to University of South China, Hengyang, Hunan, 421001, PR China.
Kai
K
Zhang
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan, 421001, PR China.
Juan
J
Peng
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan, 421001, PR China.
Ya-Ling
YL
Tang
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan, 421001, PR China.
Xiao-Hua
XH
Yu
The Second Hospital Affiliated to University of South China, Hengyang, Hunan, 421001, PR China.
Jun-Fa
JF
Zeng
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan, 421001, PR China.
Jian-Jun
JJ
Lei
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan, 421001, PR China.
Dang-Heng
DH
Wei
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan, 421001, PR China.
Zuo
Z
Wang
D001054:Apolipoproteins A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D012634:Bodily Secretions / Q000187:drug effects; D056945:Hep G2 Cells; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D050356:Lipid Metabolism; D017270:Lipoprotein(a) / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000099150:Receptor, Farnesoid X-Activated
D001054:Apolipoproteins A; D051557:Hepatocyte Nuclear Factor 4; D006862:Hydrogen Sulfide; D017270:Lipoprotein(a); D051571:Protein Kinase C-alpha; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C496592:HNF4A protein, human
apolipoprotein(a); farnesoid X receptor; hepG2 cell; hepatocyte nuclear factor 4α; hydrogen sulfide; lipoprotein (a)