Cholesterol Signaling at the Endoplasmic Reticulum Occurs in npc1−/− but Not in npc1−/−, LDLR−/− Mice
Copyright policy )Cholesterol Signaling at the Endoplasmic Reticulum Occurs in npc1−/− but Not in npc1−/−, LDLR−/− Mice
It remains controversial whether deficiency of the Niemann-Pick C1 (npc1) protein results in altered cholesterol signaling at the endoplasmic reticulum (ER). In this report, we have measured the processed, nuclear form of sterol regulatory element binding protein (SREBP)-1 in livers of npc1 wild-type, heterozygous, and homozygous deficient mice, alone, and in combination with deficiencies of the low density lipoprotein receptor (LDLR) or the multiple drug resistant (mdr)1a, P-glycoprotein. Cleavage of SREBPs to activated forms normally occurs when the ER is deficient in cholesterol. A large decrease in processed SREBP-1 was evident in fasted npc1(-/-) mice and npc1(-/-), mdr1a(-/-) mice, with no decrease evident in npc1(-/-), LDLR(-/-) mice. These results suggest that the increase in cellular cholesterol which occurs in npc1(-/-) and in npc1(-/-), mdr1a(-/-) mice includes the sites responsible for cholesterol signaling, while the similar increase in cholesterol found in npc1(-/-), LDLR(-/-) mice does not.
- University of Arizona United States
- University of Arizona College of Medicine- Phoenix United States
Male, Heterozygote, Mice, Inbred BALB C, ATP Binding Cassette Transporter, Subfamily B, Homozygote, Intracellular Signaling Peptides and Proteins, Proteins, Endoplasmic Reticulum, Mice, Mutant Strains, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Cholesterol, Liver, Receptors, LDL, Niemann-Pick C1 Protein, CCAAT-Enhancer-Binding Proteins, Animals, ATP-Binding Cassette Transporters, Female
Male, Heterozygote, Mice, Inbred BALB C, ATP Binding Cassette Transporter, Subfamily B, Homozygote, Intracellular Signaling Peptides and Proteins, Proteins, Endoplasmic Reticulum, Mice, Mutant Strains, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Cholesterol, Liver, Receptors, LDL, Niemann-Pick C1 Protein, CCAAT-Enhancer-Binding Proteins, Animals, ATP-Binding Cassette Transporters, Female
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