title: Cadmium up-regulates transcription of the steroidogenic acute regulatory protein (StAR) gene through phosphorylated CREB rather than SF-1 in K28 cells.
abstract: Cadmium is a widely used heavy metal in industry and affects the male reproductive system of animals, including humans, as a result of occupational and environmental exposures. However, the molecular mechanism underlying its effect on steroidogenesis in gonads remains unclear. In this study, we demonstrated that exposure of K28 mouse testicular Leydig tumor cells to cadmium led to a significant increase in the mRNA level, promoter activity and protein level of the steroidogenic acute regulatory protein (StAR), an essential factor for steroid biosynthesis. It has been well documented that StAR gene transcription is regulated by multiple transcription factors, including cAMP-responsive element binding protein (CREB) family members and SF-1. Cadmium treatment caused an increase in CREB phosphorylation but did not alter the CREB protein level in the nucleus. EMSA studies revealed that cadmium-induced phosphorylated CREB formed specific complexes with the proximal region of the StAR gene promoter. Furthermore, co-transfection with a CREB expression plasmid significantly increased cadmium-induced StAR promoter activity. However, the nuclear level and the affinity of SF-1 protein for the StAR proximal promoter were dramatically decreased upon exposure to cadmium. Taken together, these results suggest that cadmium up-regulates StAR gene expression through phosphorylated CREB rather than through SF-1 in mouse testicular Leydig cells.
authors: Biosafety Division, National Academy of Agricultural Science, Rural Development Administration, Korea.
authors: Soo-Yun
authors: SY
authors: Park
authors: Cynthia
authors: C
authors: Gomes
authors: Sung-Dug
authors: SD
authors: Oh
authors: Jaemog
authors: J
authors: Soh
mesh_terms: D000818:Animals; D019256:Cadmium Chloride / Q000009:adverse effects*; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007985:Leydig Cells; D008297:Male; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics*; D010766:Phosphorylation; D054339:Steroidogenic Factor 1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D010750:Phosphoproteins; D054339:Steroidogenic Factor 1; D000098682:Steroidogenic Acute Regulatory Protein; D019256:Cadmium Chloride