Mechanism of angiotensin II-induced proliferation in bovine adrenocortical cells

Rama Natarajan, Noe Gonzales, Peter J Hornsby, Jerry Nadler

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

The peptide hormone angiotensin-II (AII) is a potent vasoconstrictor and major regulator of aldosterone synthesis. In addition, AII also has growth-promoting effects. We have recently shown that the lipoxygenase (LO) pathway of arachidonic acid plays a major role in AII-induced aldosterone synthesis in adrenal glomerulosa cells. The LO pathway is also involved in the vasopressor and renin-inhibitory effects of AII. However, the role of LO products in AII-induced mitogenic effects have not yet been investigated. In the present studies we have evaluated the role of the LO pathway in AII-induced proliferative responses in a bovine adrenocortical cell clone termed AC1 cells. In addition, the potential receptor type and mechanism of AII-induced proliferation was studied by evaluating the effect of specific nonpeptide type 1 and type 2 AII receptor antagonists and the role of protein kinase-C (PKC). AII-induced DNA synthesis was significantly attenuated by two structurally dissimilar LO inhibitors, baicalein and phenidone. In addition, the LO product 12-hydroxyeicosatetraenoic acid (12-HETE) itself caused a significant increase in DNA synthesis, suggesting that the 12-LO pathway in part plays a role in AII-mediated mitogenesis. AII-induced proliferative responses were blocked by the type 1 AII receptor antagonist. Both AII- and 12-HETE-induced increases in DNA synthesis were markedly inhibited by two PKC blockers, staurosporine and sangivamycin. Further, both AII and 12-HETE could activate PKC by translocating it from the cytosol to the membrane fraction, as determined by Western immunoblotting. These results suggest that both 12-LO activation and protein kinase-C have an important role in AII-induced adrenal cell proliferation.

Original languageEnglish (US)
Pages (from-to)1174-1180
Number of pages7
JournalEndocrinology
Volume131
Issue number3
StatePublished - Sep 1992
Externally publishedYes

Fingerprint

Angiotensin II
Arachidonate 12-Lipoxygenase
Hydroxyeicosatetraenoic Acids
Protein Kinase C
Lipoxygenase
Angiotensin II Type 1 Receptor Blockers
sangivamycin
Aldosterone
DNA
Angiotensin II Type 2 Receptor Blockers
Arachidonate Lipoxygenases
Zona Glomerulosa
Lipoxygenase Inhibitors
Angiotensin Receptors
Staurosporine
Peptide Hormones
Vasoconstrictor Agents
Renin
Cytosol
Clone Cells

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Natarajan, R., Gonzales, N., Hornsby, P. J., & Nadler, J. (1992). Mechanism of angiotensin II-induced proliferation in bovine adrenocortical cells. Endocrinology, 131(3), 1174-1180.

Mechanism of angiotensin II-induced proliferation in bovine adrenocortical cells. / Natarajan, Rama; Gonzales, Noe; Hornsby, Peter J; Nadler, Jerry.

In: Endocrinology, Vol. 131, No. 3, 09.1992, p. 1174-1180.

Research output: Contribution to journalArticle

Natarajan, R, Gonzales, N, Hornsby, PJ & Nadler, J 1992, 'Mechanism of angiotensin II-induced proliferation in bovine adrenocortical cells', Endocrinology, vol. 131, no. 3, pp. 1174-1180.
Natarajan R, Gonzales N, Hornsby PJ, Nadler J. Mechanism of angiotensin II-induced proliferation in bovine adrenocortical cells. Endocrinology. 1992 Sep;131(3):1174-1180.
Natarajan, Rama ; Gonzales, Noe ; Hornsby, Peter J ; Nadler, Jerry. / Mechanism of angiotensin II-induced proliferation in bovine adrenocortical cells. In: Endocrinology. 1992 ; Vol. 131, No. 3. pp. 1174-1180.
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