TitleCharacterization and regulation of human Stearoyl-CoA Desaturase 5
NameKim, Gretchun Jungyun (author), Yam, Kit L. (chair), Igal, R. Ariel (internal member), Carman, George M. (outside member), Suh, Nanjoo (outside member), Rutgers University, Graduate School - New Brunswick,
Saturated fatty acids--Synthesis
DescriptionSaturated (SFA) and monounsaturated fatty acids (MUFA) are among the most abundant fatty acids in mammalian organisms. These fatty acids are fundamental components of structural, energetic, and signaling lipids; hence their levels have to be tightly regulated by the cell. The abundance of SFA and MUFA is determined by the rate of activity of Stearoyl-CoA Desaturase (SCD), an enzyme responsible for biosynthesis of MUFA by inserting a double bond of a saturated acyl-CoA. To date, four isoforms of SCD have been described in murine, and two isoforms in humans. Unlike ubiquitously expressed SCD1, human SCD5 is predominantly expressed in brains and pancreas. SCD1 is a critical factor of the control of cell lipogenesis, as well as cell proliferation and differentiation. Importantly, dysfunctional SCD1 is linked to the onset of several widespread diseases, including obesity, diabetes, and cancer. Despite considerable amount of research devoted to unravel the mechanisms of SCD1 regulation, the role and regulation of SCD5 is virtually unknown. In the present study, we determined the abundance of SCD5 protein in human cell lines including normal, transformed, and lung cancer cell lines. Further, we examined the role of insulin and epidermal growth factor in the regulation of SCD5 levels in normal and neoplastic human cells. Finally, since the high levels of SCD5 found in the brain suggest a possible function of this enzyme in neuronal differentiation, we examined the effect of retinoic acid on the content of SCD5 in human neuroblastoma cells. Here, we report that SCD5 is abundantly expressed in different human cell types and cell lines, and that SCD5 levels are increased by insulin, likely through the activation of the PI3K/Akt pathway, a signaling cascade that controls lipid synthesis, mitogenesis and tumorigenesis. In addition, we found a slight increased SCD5 during the process of neuronal differentiation. Thus, our findings demonstrate that the levels of SCD5 are modulated by critical factors that control cell growth, survival and differentiation in human cells. Taken together, these data suggests SCD as potential target for pharmacological and nutritional interventions in a number of human diseases and conditions.
NoteIncludes bibliographical references
Noteby Gretchun Jungyun Kim
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.