Lipoprotein lipase expression in undifferentiated hepatoma cells is regulated by progesterone and protein kinase A.
Recently, it was shown that lipoprotein lipase (LPL) was produced in neonatal but not in adult rat liver. In an attempt to further define the mechanism involved in liver LPL expression, we identified a neonatal mouse hepatoma cell line, BWTG3, capable of producing LPL. The regulation of LPL expression by various extracellular stimuli was investigated in this cell line. Progesterone caused a rise in LPL production by BWTG3 cells. Other hormones tested, such as insulin, glucagon, adrenalin, testosterone, and thyroid hormone, had no effect on LPL production. The effects of progesterone on LPL production showed slow kinetics reaching a maximum 24 h after addition. Cotransfection of a progesterone receptor expression vector with a 5'-LPL-CAT reporter construct resulted in an induction of CAT activity, suggesting that the increase in LPL accumulation after progesterone was linked to transcriptional induction of the LPL gene. Stimuli causing an elevation of protein kinase A activity in the cells also increased LPL production. Three agents capable of elevating intracellular cAMP levels, i.e., forskolin, dBcAMP, and choleratoxin, caused an elevation of LPL production. The increase in LPL activity caused by forskolin and choleratoxin was paralleled by an elevation of LPL mRNA levels, while dBcAMP only induced a small elevation of LPL mRNA levels. The increase in LPL production was shown to be linked to the stimulation of the PKA signal transduction pathway and was apparently transmitted via the transcription factor CREB. No effect of the stimulation of protein kinase C or calcium/calmodulin-dependent kinase on LPL production was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
Peinado-Onsurbe
J
J
Department of Developmental Biology, Campus Gasthuisberg, Leuven, Belgium.
Staels
B
B
Deeb
S
S
Auwerx
J
J
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D008071:Lipoprotein Lipase / Q000096:biosynthesis / Q000235:genetics*; D008114:Liver Neoplasms, Experimental; D051379:Mice; D011374:Progesterone / Q000494:pharmacology*; D011494:Protein Kinases / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured
D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D005576:Colforsin; D011374:Progesterone; D003994:Bucladesine; D002772:Cholera Toxin; D011494:Protein Kinases; D008071:Lipoprotein Lipase