Lead activates protein kinase C in immature rat brain microvessels

Jasna Markovac, Gary William Goldstein

Research output: Contribution to journalArticle

Abstract

We investigated the effects of inorganic lead upon calcium-, phospholipid-dependent protein kinase (protein kinase C) in brain microvessels isolated from 6-day-old rat pups. We found that (a) in broken cell preparations, lead at micromolar concentrations activates this enzyme to an extent equivalent to that of micromolar calcium (10.3 ± 1.3 and 9.2 ± 1.6 pmol/mg/min, respectively) and (b) preincubation ofintact microvessels with lead results in a translocation of protein kinase C from the soluble to the particulate fraction. The cytosolic kinase activity stimulated by lead has the same requirements for diacylglycerol and phospholipid as the calcium-stimulated enzyme, suggesting that lead activates the kinase by mimicking calcium. The hypothesis that lead affects protein kinase C activity through a mechanism similar to that of calcium is supported by the similar time courses of substrate phosphorylation and dephosphorylation mediated by lead and calcium. When intact microvessels are preincubated with micromolar concentrations of lead, the translocation of protein kinase C occurs in a dose- and time-dependent manner. The relocalization is virtually complete at 0.1 μm lead and by 30 min of exposure. We propose that the sensitivity of protein kinase C to lead, described here in immature brain microvessels, makes this regulatory enzyme a potential mediator of lead toxicity.

Original languageEnglish (US)
Pages (from-to)14-23
Number of pages10
JournalToxicology and Applied Pharmacology
Volume96
Issue number1
DOIs
StatePublished - 1988
Externally publishedYes

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Microvessels
Protein Kinase C
Rats
Brain
Calcium
Phosphotransferases
Enzymes
Phosphorylation
Lead
Diglycerides
Toxicity
Phospholipids
Substrates

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Lead activates protein kinase C in immature rat brain microvessels. / Markovac, Jasna; Goldstein, Gary William.

In: Toxicology and Applied Pharmacology, Vol. 96, No. 1, 1988, p. 14-23.

Research output: Contribution to journalArticle

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