Regulation of the scavenger receptor BI and the LDL receptor by activators of aldosterone production, angiotensin II and PMA, in the human NCI-H295R adrenocortical cell line

Biochim Biophys Acta. 2003 Apr 8;1631(3):218-28. doi: 10.1016/s1388-1981(03)00020-9.

Abstract

In human adrenal cells, cholesterol for steroidogenesis is derived from both high-density lipoproteins (HDL) via the Scavenger Receptor Class B Type I (SR-BI) and low-density lipoproteins (LDL) via the LDL receptor pathway. We have previously shown that, in the human adrenocortical carcinoma cell line, NCI-H295R, SR-BI and LDL receptor expression and steroidogenesis are coordinately regulated by activators of protein kinase A (PKA) leading to glucocorticoid synthesis. In the present study, we studied whether SR-BI and LDL receptor expression are regulated by activators of the protein kinase C (PKC) signaling pathway, such as angiotensin II, which stimulate mineralocorticoid synthesis. First, it is shown that, in NCI-H295R cells, aldosterone synthesis is stimulated by a phorbol ester (phorbol-12-myristate-13 acetate, PMA), a potent PKC activator. Northern blot analysis indicated that both angiotensin II and PMA stimulated SR-BI expression in a time-dependent manner. LDL receptor expression is slightly stimulated by PMA. The induction of SR-BI gene expression occurs at the transcriptional level, via an activation of the human SR-BI promoter, as shown by transient transfection experiments. Finally, SR-BI protein level was increased in angiotensin II- and PMA-stimulated cells, resulting in higher lipoprotein binding and specific cholesteryl ester (CE) uptake from HDL, as well from LDL after angiotensin II and PMA stimulation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex / drug effects*
  • Adrenal Cortex / metabolism
  • Aldosterone / biosynthesis*
  • Aldosterone / metabolism
  • Angiotensin II / pharmacology*
  • CD36 Antigens
  • Cholesterol Esters / metabolism
  • Cholesterol, HDL / metabolism
  • Cholesterol, LDL / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Membrane Proteins*
  • RNA, Messenger / biosynthesis
  • Receptors, Immunologic / biosynthesis
  • Receptors, Immunologic / metabolism*
  • Receptors, LDL / biosynthesis
  • Receptors, LDL / metabolism*
  • Receptors, Lipoprotein*
  • Receptors, Scavenger
  • Scavenger Receptors, Class B
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Tumor Cells, Cultured

Substances

  • CD36 Antigens
  • Cholesterol Esters
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Membrane Proteins
  • RNA, Messenger
  • Receptors, Immunologic
  • Receptors, LDL
  • Receptors, Lipoprotein
  • Receptors, Scavenger
  • SCARB1 protein, human
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B
  • Angiotensin II
  • Aldosterone
  • Tetradecanoylphorbol Acetate