Steroidogenic impairment due to reduced ovarian transcription of cytochrome P450 side-chain-cleavage (P450scc) and steroidogenic acute regulatory protein (StAR) during experimental nephrotic syndrome

Life Sciences ◽  
2006 ◽  
Vol 79 (7) ◽  
pp. 702-708 ◽  
Author(s):  
Miguel Peña-Rico ◽  
María Guadalupe Ortiz-López ◽  
Luz Camacho-Castillo ◽  
Mario Cárdenas ◽  
José Pedraza-Chaverri ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Cytochrome P450 ◽  
Regulatory Protein ◽  
Steroidogenic Acute Regulatory Protein ◽  
Side Chain ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Steroidogenic Acute Regulatory

scholarly journals Salt-Inducible Kinase Is Involved in the ACTH/cAMP-Dependent Protein Kinase Signaling in Y1 Mouse Adrenocortical Tumor Cells

2001 ◽  
Vol 15 (8) ◽  
pp. 1264-1276 ◽  
Author(s):  
Xing-zi Lin ◽  
Hiroshi Takemori ◽  
Yoshiko Katoh ◽  
Junko Doi ◽  
Nanao Horike ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Promoter Activity ◽  
Regulatory Protein ◽  
Steroidogenic Acute Regulatory Protein ◽  
Side Chain ◽  
Mrna Levels ◽  
Steroidogenic Factor 1 ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Steroidogenic Acute Regulatory

Abstract The involvement of salt-inducible kinase, a recently cloned protein serine/threonine kinase, in adrenal steroidogenesis was investigated. When Y1 mouse adrenocortical tumor cells were stimulated by ACTH, the cellular content of salt-inducible kinase mRNA, protein, and enzyme activity changed rapidly. Its level reached the highest point in 1–2 h and returned to the initial level after 8 h. The mRNA levels of cholesterol side-chain cleavage cytochrome P450 and steroidogenic acute regulatory protein, on the other hand, began to rise after a few hours, reaching the highest levels after 8 h. The salt-inducible kinase mRNA level in ACTH-, forskolin-, or 8-bromo-cAMP-treated Kin-7 cells, mutant Y1 with less cAMP-dependent PKA activity, remained low. However, Kin-7 cells, when transfected with a PKA expression vector, expressed salt-inducible kinase mRNA. Y1 cells that overexpressed salt-inducible kinase were isolated, and the mRNA levels of steroidogenic genes in these cells were compared with those in the parent Y1. The level of cholesterol side-chain cleavage cytochrome P450 mRNA in the salt-inducible kinase-overexpressing cells was markedly low compared with that in the parent, while the levels of Ad4BP/steroidogenic factor-1-, ACTH receptor-, and steroidogenic acute regulatory protein-mRNAs in the former were similar to those in the latter. The ACTH-dependent expression of cholesterol side-chain cleavage cytochrome P450- and steroidogenic acute regulatory protein-mRNAs in the salt-inducible kinase-overexpressing cells was significantly repressed. The promoter activity of the cholesterol side-chain cleavage cytochrome P450 gene was assayed by using Y1 cells transfected with a human cholesterol side-chain cleavage cytochrome P450 promoter-linked reporter gene. Addition of forskolin to the culture medium enhanced the cholesterol side-chain cleavage cytochrome P450 promoter activity, but the forskolin-dependently activated promoter activity was inhibited when the cells were transfected with a salt-inducible kinase expression vector. This inhibition did not occur when the cells were transfected with a salt-inducible kinase (K56M) vector that encoded an inactive kinase. The salt-inducible kinase’s inhibitory effect was also observed when nonsteroidogenic, nonAd4BP/steroidogenic factor-1 -expressing, NIH3T3 cells were used for the promoter assays. These results suggested that salt-inducible kinase might play an important role(s) in the cAMP-dependent, but Ad4BP/steroidogenic factor-1-independent, gene expression of cholesterol side-chain cleavage cytochrome P450 in adrenocortical cells.

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