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 language | English (US) |
|---|---|
| Pages (from-to) | 14-23 |
| Number of pages | 10 |
| Journal | Toxicology and Applied Pharmacology |
| Volume | 96 |
| Issue number | 1 |
| DOIs | |
| State | Published - 1988 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Lead activates protein kinase C in immature rat brain microvessels
AU - Markovac, Jasna
AU - Goldstein, Gary William
PY - 1988
Y1 - 1988
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0023689854&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023689854&partnerID=8YFLogxK
U2 - 10.1016/0041-008X(88)90242-6
DO - 10.1016/0041-008X(88)90242-6
M3 - Article
C2 - 3188018
AN - SCOPUS:0023689854
VL - 96
SP - 14
EP - 23
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
SN - 0041-008X
IS - 1
ER -