title: Redundant pathways for negative feedback regulation of bile acid production.
abstract: The orphan nuclear hormone receptor SHP has been proposed to have a key role in the negative feedback regulation of bile acid production. Consistent with this, mice lacking the SHP gene exhibit mild defects in bile acid homeostasis and fail to repress cholesterol 7-alpha-hydroxylase expression in response to a specific agonist for the bile acid receptor FXR. However, this repression is retained in SHP null mice fed bile acids, demonstrating the existence of compensatory repression pathways of bile acid signaling. We provide evidence for two such pathways, based on activation of the xenobiotic receptor PXR or the c-Jun N-terminal kinase JNK. We conclude that redundant mechanisms regulate this critical aspect of cholesterol homeostasis.
authors.affiliation: Department of Molecular and Cellular Biology, Houston, TX 77030, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Yoon-Kwang
authors.initials: YK
authors.lastname: Lee
authors.forename: Donnie
authors.initials: D
authors.lastname: Bundman
authors.forename: Yunqing
authors.initials: Y
authors.lastname: Han
authors.forename: Sundararajah
authors.initials: S
authors.lastname: Thevananther
authors.forename: Chang Soo
authors.initials: CS
authors.lastname: Kim
authors.forename: Steven S
authors.initials: SS
authors.lastname: Chua
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.forename: Richard A
authors.initials: RA
authors.lastname: Heyman
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
authors.forename: David D
authors.initials: DD
authors.lastname: Moore
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000096:biosynthesis / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D019826:Cholic Acid / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000378:metabolism; D005246:Feedback / Q000502:physiology*; D006706:Homeostasis; D007555:Isoxazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009539:Nicotinic Acids / Q000494:pharmacology; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D047488:Retinoid X Receptors; D013234:Stem Cells / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014157:Transcription Factors / Q000819:agonists / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D002790:Cholesterol 7-alpha-Hydroxylase; D019826:Cholic Acid; D004268:DNA-Binding Proteins; D007555:Isoxazoles; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D009539:Nicotinic Acids; D009687:Nuclear Proteins; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011987:Receptors, Steroid; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated; C099713:nuclear receptor subfamily 0, group B, member 2; C412815:GW 4064; C095104:LG 100268