期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 63, 期 23, 页码 2829-2837出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-006-6325-y
关键词
high-density lipoprotein (HDL); apolipoprotein A-I; cholesterol; hepatocyte; nucleotide metabolism; adenylate kinase; nucleoside diphosphokinase
We have previously demonstrated on human hepatocytes that apolipoprotein A-I binding to an ecto-F-1-ATPase stimulates the production of extracellular ADP that activates a P2Y(13)-mediated high-density lipoprotein (HDL) endocytosis pathway. Therefore, we investigated the mechanisms controlling the extracellular ATP/ADP level in hepatic cell lines and primary cultures to determine their impact on HDL endocytosis. Here we show that addition of ADP to the cell culture medium induced extracellular ATP production that was due to adenylate kinase (AK; 2ADP reversible arrow ATP + AMP) and nucleoside diphosphokinase (NDPK; ADP + NTP reversible arrow ATP + NDP) activities, but not to ATP synthase activity. We further observed that in vitro modulation of both ecto-NDPK and AK activities could regulate the ADP-dependent HDL endocytosis. But interestingly, only AK appeared to naturally participate in the pathway by consuming the ADP generated by the ecto-F-1-ATPase. Thus controlling the extracellular ADP level is a potential target for reverse cholesterol transport regulation.
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