title: Regulation of gap junction function and Connexin 43 expression by cytochrome P450 oxidoreductase (CYPOR).
abstract: Cytochrome P450 oxidoreductase (CYPOR) is a microsomal electron-transferring enzyme containing both FAD and FMN as co-factors, which provides the reducing equivalents to various redox partners, such as cytochromes P450 (CYPs), heme oxygenase (HO), cytochrome b(5) and squalene monooxygenase. Human patients with severe forms of CYPOR mutation show bone defects such as cranio- and humeroradial synostoses and long bone fractures, known as Antley-Bixler-like Syndrome (ABS). To elucidate the role of CYPOR in bone, we knocked-down CYPOR in multiple osteoblast cell lines using RNAi technology. In this study, knock-down of CYPOR decreased the expression of Connexin 43 (Cx43), known to play a critical role in bone formation, modeling, and remodeling. Knock-down of CYPOR also decreased Gap Junction Intercellular Communication (GJIC) and hemichannel activity. Promoter luciferase assays revealed that the decrease in expression of Cx43 in CYPOR knock-down cells was due to transcriptional repression. Primary osteoblasts isolated from bone specific Por knock-down mice calvariae confirmed the findings in the cell lines. Taken together, our study provides novel insights into the regulation of gap junction function by CYPOR and suggests that Cx43 may play an important role(s) in CYPOR-mediated bone defects seen in patients.
authors: The University of Texas Health Science Center at San Antonio, Department of Biochemistry, San Antonio, TX 78229, United States.
authors: Srikanth R
authors: SR
authors: Polusani
authors: Rekha
authors: R
authors: Kar
authors: Manuel A
authors: MA
authors: Riquelme
authors: Bettie Sue
authors: BS
authors: Masters
authors: Satya P
authors: SP
authors: Panda
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018031:Connexin 43 / Q000235:genetics*; D017629:Gap Junctions / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics / Q000502:physiology*; D010012:Osteogenesis / Q000235:genetics*
chemical_list: D018031:Connexin 43; D009251:NADPH-Ferrihemoprotein Reductase