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Lead‐dependent effects on arachidonic acid accumulation and the proliferation of vascular smooth muscle
Author(s) -
Dorman Robert V.,
Freeman Ernest J.
Publication year - 2002
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.10045
Subject(s) - arachidonic acid , dna synthesis , vascular smooth muscle , cell growth , angiotensin ii , endocrinology , trypan blue , chemistry , medicine , biology , biochemistry , cell , dna , receptor , enzyme , smooth muscle
Lead (Pb 2+ ) has been implicated in the development of hypertension and atherosclerosis. The proliferation of vascular smooth muscle cells (VSMC) is a central feature of both conditions and there is evidence that Pb 2+ potentiates serum‐dependent cell growth. The aim of this work was to examine the role of phospholipase A 2 in mitogen‐dependent VSMC proliferation and determine if Pb 2+ interacts with this system in order to potentiate mitotic events. It was observed that cell proliferation induced by angiotensin II, or fetal bovine serum, required the activation of a Ca 2+ ‐dependent cytosolic phospholipase A 2 and the subsequent release of unesterified arachidonic acid. This path was affected by Pb 2+ as the metal increased the amount of arachidonic acid accumulation induced by either mitogen. In addition, Pb 2+ potentiated mitogen‐induced DNA synthesis when present at lower doses (0.02 or 0.2 mg%), but had no effect on DNA synthesis, or cell numbers, in unstimulated cells. However, a high dose (2 mg%) of Pb 2+ attenuated the DNA synthesis stimulated by angiotensin II, or serum, but induced the accumulation of unesterified arachidonic acid in unstimulated cells. A biphasic effect of Pb 2+ on cell numbers and viability was also observed as 0.02 or 0.2 mg% Pb 2+ did not affect cell numbers or trypan blue exclusion in unstimulated cells, while 2 mg% Pb 2+ reduced cell numbers and viability. It appeared, therefore, that the lower concentrations of Pb 2+ increased arachidonic acid release and DNA synthesis only in stimulated VSMC, perhaps due to further activation of a Ca 2+ ‐dependent processes. In contrast, the high dose of Pb 2+ reduced DNA synthesis in stimulated cells and reduced cell numbers and viability in unstimulated cells, which may relate to the noted increase in unesterified arachidonic acid. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:245–253, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10045