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Updated: Jul 20, 2026

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

Protein kinase C beta and delta isoenzymes mediate cholesterol accumulation in PMA-activated macrophages

Hong-Tao Ma1, Wan-Wan Lin, Bin Zhao

  • 1Section of Experimental Atherosclerosis, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1422, USA.

Biochemical and Biophysical Research Communications
|August 26, 2006
PubMed

Insights

Protein kinase C (PKC) isoenzymes, specifically beta and likely delta, mediate cholesterol accumulation in macrophages. This process is crucial for foam cell formation in cardiovascular disease.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Immunology

Background:

  • Phorbol 12-myristate 13-acetate (PMA) activation of human monocyte-derived macrophages stimulates low-density lipoprotein (LDL) macropinocytosis.
  • This process transforms macrophages into foam cells, a key event in atherosclerosis.
  • The specific protein kinase C (PKC) isoenzymes involved in this cholesterol accumulation were previously unidentified.

Purpose of the Study:

  • To identify the PKC isoenzymes responsible for mediating cholesterol accumulation in PMA-activated human macrophages incubated with LDL.
  • To elucidate the role of specific PKC isoenzymes in the transformation of macrophages into foam cells.

Main Methods:

  • Utilized pan PKC inhibitors (Go6850, Go6983, RO 32-0432) and a classical group PKC inhibitor (Go6976) to assess cholesterol accumulation.
  • Employed a pseudosubstrate myristoylated peptide inhibitor for PKC alpha and beta.
  • Used small molecule inhibitors specific for PKC alpha (HBDDE) and PKC beta (LY333513) to determine their individual contributions.

Main Results:

  • Pan PKC inhibitors significantly inhibited cholesterol accumulation (>85%), while the classical group inhibitor showed ~50% inhibition.
  • PKC beta was identified as the classical group isoenzyme mediating PMA-stimulated cholesterol accumulation.
  • PKC beta inhibition (LY333513) fully accounted for the classical group's contribution, while PKC alpha inhibition (HBDDE) had minimal effect.

Conclusions:

  • Cholesterol accumulation in PMA-activated macrophages involves both PKC beta and another PKC isoenzyme, likely PKC delta.
  • These findings highlight the specific PKC isoenzymes involved in LDL-induced foam cell formation.
  • Understanding these pathways offers potential therapeutic targets for atherosclerosis.

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