AIDS (London, England) · 2002
Indinavir inhibits sterol-regulatory element-binding protein-1c-dependent lipoprotein lipase and fatty acid synthase gene activations.
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Miserez André R, Muller Patrick Y, Spaniol Violeta
Аннотация
BACKGROUND: A syndrome characterized by hypertriglyceridaemia, hypercholesterolaemia, hyperinsulinaemia, and lipodystrophy has been found to be associated with highly active antiretroviral treatment (HAART) including protease inhibitors. A marker predicting this syndrome has been previously identified in the gene encoding the sterol-regulatory element-binding protein (SREBP)-1c, a regulator of triglycerides, cholesterol, insulin, and adipocytes.
OBJECTIVE: A possible inhibition of SREBP-1c-dependent genes by the protease inhibitor indinavir and its possible reversal by the lipid-lowering drug simvastatin were studied.
METHODS: The effects of indinavir and simvastatin on the inhibition/activation of SREBP-1c-dependent genes were compared with the effects of indinavir and simvastatin on the inhibition/activation of SREBP-1c-independent genes.
RESULTS: Indinavir inhibited the SREBP-1c-dependent genes encoding the lipoprotein lipase (103 nmol/l resulted in an inhibition of 12.4%; P = 0.0051) and the fatty acid synthase (103 nmol/l resulted in an inhibition of 30.3%; P = 0.036) in a dose-dependent fashion but not the SREBP-1c-independent gene encoding the low-density lipoprotein receptor. Simvastatin antagonized the indinavir-induced SREBP-1c-inhibition.
CONCLUSIONS: Indinavir inhibits important effector genes of the SREBP-1c pathway, explaining major HAART-related adverse effects.
OBJECTIVE: A possible inhibition of SREBP-1c-dependent genes by the protease inhibitor indinavir and its possible reversal by the lipid-lowering drug simvastatin were studied.
METHODS: The effects of indinavir and simvastatin on the inhibition/activation of SREBP-1c-dependent genes were compared with the effects of indinavir and simvastatin on the inhibition/activation of SREBP-1c-independent genes.
RESULTS: Indinavir inhibited the SREBP-1c-dependent genes encoding the lipoprotein lipase (103 nmol/l resulted in an inhibition of 12.4%; P = 0.0051) and the fatty acid synthase (103 nmol/l resulted in an inhibition of 30.3%; P = 0.036) in a dose-dependent fashion but not the SREBP-1c-independent gene encoding the low-density lipoprotein receptor. Simvastatin antagonized the indinavir-induced SREBP-1c-inhibition.
CONCLUSIONS: Indinavir inhibits important effector genes of the SREBP-1c pathway, explaining major HAART-related adverse effects.