Angiotensin-II acute regulation of rapid response genes in human, bovine, and rat adrenocortical cells.
Angiotensin-II (Ang-II) regulates adrenal steroid production and gene transcription through several signaling pathways. Changes in gene transcription occur within minutes after Ang-II stimulation, causing an increase in aldosterone production and subsequent increase in the overall capacity to produce aldosterone. Our goal was to compare the Ang-II regulation of early gene expression and confirm the up-regulation of selected genes using quantitative real-time RT-PCR (qPCR) across three species, such as, human, bovine, and rat. Microarray analyses were performed using samples from control and Ang-II (10 nM)-treated (1 h) cells from human adrenocortical tumor cell line H295R, and primary adrenal glomerulosa cells from bovine and rat, applied respectively to human, bovine, and rat chips. qPCR was performed to confirm up-regulation of selected genes using mRNA. The microarray comparison revealed 18% similarity among the top 50 up-regulated genes, with human/rat, 20%; human/bovine, 36%; and rat/bovine, 26% similarity. The gene list generated by this comparison included: activating transcription factor 3, B-cell translocation gene (BTG2), Nuclear receptor subfamily 4, group A, member 1 (NR4A1), NR4A2, NR4A3, early growth response 1, v-fos FBJ murine osteosarcoma viral oncogene homolog (c-FOS), FOSB, and Jun family member B (JUNB). Pretreatment of H295R cells with cycloheximide had no effect on Ang-II induction of these genes, suggesting that they are direct targets of Ang-II signaling. The Ang-II gene targets have been defined in three different adrenocortical model systems. Several of the listed genes have previously been described as being key regulators of adrenocortical function. The presence of adrenal cell common genes in such distinct cell models strengthens the hypothesis that these genes are regulators of aldosterone production.
Nogueira
Edson F
EF
Department of Physiology and Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912, USA.
Vargas
Claudia A
CA
Otis
Mélissa
M
Gallo-Payet
Nicole
N
Bollag
Wendy B
WB
Rainey
William E
WE
D000302:Adrenal Cortex / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D051381:Rats; D013045:Species Specificity; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000804:Angiotensin II