Inhibition of mitochondrial superoxide generation in rat alveolar macrophages by 12-O-tetradecanoylphorbol-13-acetate potential role of protein kinase C

S. J. Rembish, Y. Yang, M. A. Trush

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

We have observed that lucigenin-derived chemiluminescence (CL) measures superoxide anion (O2) production from two major cellular compartments in rat alveolar macrophages (AMs): extracellular O2/- produced by NADPH oxidase; and intracellular O2/- produced by the reduction of molecular oxygen by the mitochondrial electron transport chain. Although the treatment of AMs with 30 ng/mL 12-O-tetradecanoyl phorbol-13-acetate (TPA) increases the production of O2/- by NADPH oxidase, the net result of TPA addition monitors is a decrease in lucigenin-derived CL resulting from inhibition of mitochondrial- derived O2/- production. Since protein kinase C (PKC) has been shown to be the cellular receptor through which TPA mediates its effects, it was postulated that activation of PKC inhibits mitochondrial-derived O2/- production as measured by lucigenin-derived CL. Studies performed with 50 μM H-7 (a PKC inhibitor) support this hypothesis by blocking the inhibition of mitochondrial-derived CL by TPA, while HA-1004, a negative control for H-7, had no effect on the system. These results suggest that mitochondrial respiration may be modulated by the actions of PKC. Moreover, this observation suggests a novel mechanism whereby chemicals which activate PKC may affect cellular function through modulation of mitochondrial activity.

Original languageEnglish (US)
Title of host publicationResearch Communications in Molecular Pathology and Pharmacology
Pages115-129
Number of pages15
Volume85
Edition2
StatePublished - 1994

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Alveolar Macrophages
Tetradecanoylphorbol Acetate
Superoxides
Protein Kinase C
Luminescence
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
NADPH Oxidase
Protein C Inhibitor
Protein Kinase Inhibitors
Electron Transport
Respiration
Oxygen
10,10'-dimethyl-9,9'-biacridinium

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Rembish, S. J., Yang, Y., & Trush, M. A. (1994). Inhibition of mitochondrial superoxide generation in rat alveolar macrophages by 12-O-tetradecanoylphorbol-13-acetate potential role of protein kinase C. In Research Communications in Molecular Pathology and Pharmacology (2 ed., Vol. 85, pp. 115-129)

Inhibition of mitochondrial superoxide generation in rat alveolar macrophages by 12-O-tetradecanoylphorbol-13-acetate potential role of protein kinase C. / Rembish, S. J.; Yang, Y.; Trush, M. A.

Research Communications in Molecular Pathology and Pharmacology. Vol. 85 2. ed. 1994. p. 115-129.

Research output: Chapter in Book/Report/Conference proceedingChapter

Rembish, SJ, Yang, Y & Trush, MA 1994, Inhibition of mitochondrial superoxide generation in rat alveolar macrophages by 12-O-tetradecanoylphorbol-13-acetate potential role of protein kinase C. in Research Communications in Molecular Pathology and Pharmacology. 2 edn, vol. 85, pp. 115-129.
Rembish SJ, Yang Y, Trush MA. Inhibition of mitochondrial superoxide generation in rat alveolar macrophages by 12-O-tetradecanoylphorbol-13-acetate potential role of protein kinase C. In Research Communications in Molecular Pathology and Pharmacology. 2 ed. Vol. 85. 1994. p. 115-129
Rembish, S. J. ; Yang, Y. ; Trush, M. A. / Inhibition of mitochondrial superoxide generation in rat alveolar macrophages by 12-O-tetradecanoylphorbol-13-acetate potential role of protein kinase C. Research Communications in Molecular Pathology and Pharmacology. Vol. 85 2. ed. 1994. pp. 115-129
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