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Reciprocal relationship between reactive oxygen species and cyclooxygenase‐2 after lead exposure on vascular smooth muscle cells (700.6)
Author(s) -
Simões Maylla,
Aguado Andrea,
Zhenyukh Olha,
Alonso Maria,
Briones Ana,
Fiorim Jonaína,
Azevedo Bruna,
Vassallo Dalton,
Salaices Mercedes
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.700.6
Subject(s) - nadph oxidase , oxidative stress , reactive oxygen species , apocynin , superoxide , downregulation and upregulation , chemistry , cyclooxygenase , vascular smooth muscle , nox , celecoxib , superoxide dismutase , pharmacology , endocrinology , medicine , biochemistry , enzyme , gene , smooth muscle , organic chemistry , combustion
Studies reported that chronic lead (Pb) administration affects cardiovascular parameters. We evaluate the effects of chronic exposure to lead in vascular smooth muscle cells (VCMS) on oxidative stress and cyclooxygenase‐2 (COX‐2) pathways. Aortas were isolated from male Sprague‐Dawley rats and processed to obtain primary cultures of VCMS. The cells were stimulated with Pb (200 ng/ml) for 48 h. Pb increased the gene expression of COX‐2 and subunits of NOX‐1 and NOX‐4 of NADPH Oxidase and the protein expression of Mn‐SOD and COX‐2. Celecoxib (10μmol/L) reversed the upregulation of NOX‐1 and NOX‐4 whereas tempol (10μmol/L) reversed the upregulation of COX‐2. NADPH oxidase activity and superoxide anion production was also enhanced by Pb and normalized by Celecoxib and Rofecoxib (10μmol/L), ML171 (10μmol/L) and/or Tempol, Mito‐TEMPO (5μmol/L). Pb also induces the activation of ERK1/2 and p38MAPK signaling pathways that were involved in the augmented expression of COX‐2, NOX‐1 and NOX‐4. Pb exposure did not induce proliferation or migration of VCMS. Our results suggest a relationship between lead, COX‐2 and oxidative stress, probably involving mechanisms with MAPK signaling pathways. Since this may be involved in hypertension development, lead exposure should be considered an environmental risk factor for cardiovascular disease. Grant Funding Source : MINECO (SAF 2012‐36400) ISCIII (RD/0042/0024), FMM, CAPES, PRONEX‐FAPES/CNPq