title: Lead activates protein kinase C in immature rat brain microvessels.
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 of intact 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 microM 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.
authors.affiliation: Department of Pediatrics, University of Michigan Medical School, Ann Arbor 48109-0570.
authors.forename: J
authors.initials: J
authors.lastname: Markovac
authors.forename: G W
authors.initials: GW
authors.lastname: Goldstein
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002560:Cerebrovascular Circulation; D004305:Dose-Response Relationship, Drug; D007854:Lead / Q000494:pharmacology*; D008833:Microcirculation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D007854:Lead; D011493:Protein Kinase C; D002118:Calcium