Mercury exposure increases circulating net matrix metalloproteinase (MMP)-2 and MMP-9 activities.
Mercury (Hg) exposure causes health problems that may result from increased oxidative stress and matrix metalloproteinase (MMP) levels. We investigated whether there is an association between the circulating levels of MMP-2, MMP-9, their endogenous inhibitors (the tissue inhibitors of metalloproteinases; TIMPs) and the circulating Hg levels in 159 subjects environmentally exposed to Hg. Blood and plasma Hg were determined by inductively coupled plasma-mass spectrometry (ICP-MS). MMP and TIMP concentrations were measured in plasma samples by gelatin zymography and ELISA respectively. Thiobarbituric acid-reactive species (TBARS) were measured in plasma to assess oxidative stress. Selenium (Se) levels were determined by ICP-MS because it is an antioxidant. The relations between bioindicators of Hg and the metalloproteinases levels were examined using multivariate regression models. While we found no relation between blood or plasma Hg and MMP-9, plasma Hg levels were negatively associated with TIMP-1 and TIMP-2 levels, and thereby with increasing MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios, thus indicating a positive association between plasma Hg and circulating net MMP-9 and MMP-2 activities. These findings provide a new insight into the possible biological mechanisms of Hg toxicity, particularly in cardiovascular diseases.
Jacob-Ferreira
Anna L B
AL
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil.
Passos
Carlos J S
CJ
Jordão
Alceu A
AA
Fillion
Myriam
M
Mergler
Donna
D
Lemire
Mélanie
M
Gerlach
Raquel F
RF
Barbosa
Fernando
F
Tanus-Santos
Jose E
JE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil; D003430:Cross-Sectional Studies; D004591:Electrophoresis, Polyacrylamide Gel; D004781:Environmental Exposure / Q000009:adverse effects* / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008628:Mercury / Q000097:blood* / Q000633:toxicity*; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D012044:Regression Analysis; D012643:Selenium / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood; D055815:Young Adult
C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D017392:Thiobarbituric Acid Reactive Substances; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008628:Mercury; D012643:Selenium