title: Oxygen as a regulator of MA-10 cell functions: effect of cobalt chloride on vascular endothelial growth factor production.
abstract: Mammalian testis functions at a temperature and oxygen tension (pO(2)) lower than the core body. Hypoxia-inducible factor-1α (HIF-1α) mediates the adaptive responses to hypoxia such as production of angiogenic vascular endothelial growth factor (VEGF) in a variety of cells and tissues. VEGF production in Leydig cells is stimulated by luteinising hormone (LH)/cAMP. We have conducted experiments to find out whether HIF-1α is involved in LH/cAMP-induced secretion of VEGF by Leydig cell-derived MA-10 cells. Both cobalt chloride (CoCl(2)), an inducer of hypoxia, and 8-Br-cAMP enhanced HIF-1α activity followed by an increase in VEGF secretion. However, there was no change in mRNA levels of HIF-1α. Inhibition of HIF-1α activity by cyclosporine A (CsA) inhibited a rise in VEGF production in response to CoCl(2) as well as 8-Br-cAMP. Inhibitors of protein kinase A (PKA), extracellular regulated kinase 1/2 (ERK1/2) and phosphatidyl inositol-3 kinase/Akt (PI3-K/Akt) inhibited the increase in VEGF levels in response to both CoCl(2) and 8-Br-cAMP. The data suggest that HIF-1α is a mediator of hypoxia- as well as 8-Br-cAMP-stimulated production of VEGF in MA-10 cells; both the stimuli act through a common signalling cascade.
authors: Department of Reproductive Biology, All India Institute of Medical Sciences, New Delhi, India. anandkumarrepbiol@hotmail.com
authors: A
authors: A
authors: Kumar
authors: L
authors: L
authors: Rani
authors: B
authors: B
authors: Dhole
authors: P K
authors: PK
authors: Chaturvedi
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003035:Cobalt / Q000494:pharmacology*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D051379:Mice; D010100:Oxygen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D017931:DNA Primers; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D003035:Cobalt; C018021:cobaltous chloride; D010100:Oxygen