PMID- 20181798 OWN - NLM STAT- MEDLINE DCOM- 20100409 LR - 20141120 IS - 1945-7170 (Electronic) IS - 0013-7227 (Linking) VI - 151 IP - 4 DP - 2010 Apr TI - Angiotensin II-induced expression of brain-derived neurotrophic factor in human and rat adrenocortical cells. PG - 1695-703 LID - 10.1210/en.2009-1060 [doi] AB - Angiotensin II (Ang II) is a major regulator of steroidogenesis in adrenocortical cells, and is also an effective inducer of cytokine and growth factor synthesis in several cell types. In microarray analysis of H295R human adrenocortical cells, the mRNA of brain-derived neurotrophic factor (BDNF), a neurotrophin widely expressed in the nervous system, was one of the most up-regulated genes by Ang II. The aim of the present study was the analysis of the Ang II-induced BDNF expression and BDNF-induced effects in adrenocortical cells. Real-time PCR studies have shown that BDNF is expressed in H295R and rat adrenal glomerulosa cells. In H295R cells, the kinetics of Ang II-induced BDNF expression was faster than that of aldosterone synthase (CYP11B2). Inhibition of calmodulin kinase by KN93 did not significantly affect the Ang II-induced stimulation of BDNF expression, suggesting that it occurs by a different mechanism from the CYP11B2-response. Ang II also caused candesartan-sensitive, type-1 Ang II receptor-mediated stimulation of BDNF gene expression in primary rat glomerulosa cells. In rat adrenal cortex, BDNF protein was localized to the subcapsular region. Ang II increased BDNF protein levels both in human and rat cells, and BDNF secretion of H295R cells. Ang II also increased type-1 Ang II receptor-mediated BDNF expression in vivo in furosemide-treated rats. In rat glomerulosa cells, BDNF induced tropomyosin-related kinase B receptor-mediated stimulation of EGR1 and TrkB expression. These data demonstrate that Ang II stimulates BDNF expression in human and rat adrenocortical cells, and BDNF may have a local regulatory function in adrenal glomerulosa cells. FAU - Szekeres, Maria AU - Szekeres M AD - Department of Physiology, Budapest, Hungary. FAU - Nadasy, Gyorgy L AU - Nadasy GL FAU - Turu, Gabor AU - Turu G FAU - Supeki, Katinka AU - Supeki K FAU - Szidonya, Laszlo AU - Szidonya L FAU - Buday, Laszlo AU - Buday L FAU - Chaplin, Tracy AU - Chaplin T FAU - Clark, Adrian J L AU - Clark AJ FAU - Hunyady, Laszlo AU - Hunyady L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100224 PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (Agtr1a protein, mouse) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) RN - 0 (Receptor, Angiotensin, Type 1) RN - 11128-99-7 (Angiotensin II) RN - EC 1.14.15.4 (Cytochrome P-450 CYP11B2) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) SB - IM MH - Adrenal Cortex/cytology/*drug effects/metabolism MH - Analysis of Variance MH - Angiotensin II/*pharmacology MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Calcium-Calmodulin-Dependent Protein Kinases/genetics/metabolism MH - Cell Line MH - Cells, Cultured MH - Cytochrome P-450 CYP11B2/genetics/metabolism MH - Dose-Response Relationship, Drug MH - Gene Expression/genetics MH - Humans MH - Immunoassay MH - Immunohistochemistry MH - Male MH - Microscopy, Confocal MH - RNA, Messenger/genetics/metabolism MH - Rats MH - Rats, Wistar MH - Receptor, Angiotensin, Type 1/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tissue Array Analysis EDAT- 2010/02/26 06:00 MHDA- 2010/04/10 06:00 CRDT- 2010/02/26 06:00 PHST- 2010/02/26 06:00 [entrez] PHST- 2010/02/26 06:00 [pubmed] PHST- 2010/04/10 06:00 [medline] AID - en.2009-1060 [pii] AID - 10.1210/en.2009-1060 [doi] PST - ppublish SO - Endocrinology. 2010 Apr;151(4):1695-703. doi: 10.1210/en.2009-1060. Epub 2010 Feb 24.