Lead exposure raises superoxide and hydrogen peroxide in human endothelial and vascular smooth muscle cells. Kidney Int 2004 Dec;66(6):2329-36
Date
12/01/2004Pubmed ID
15569323DOI
10.1111/j.1523-1755.2004.66032.xScopus ID
2-s2.0-21644466520 (requires institutional sign-in at Scopus site) 84 CitationsAbstract
BACKGROUND: Chronic lead exposure causes hypertension and cardiovascular disease, which are associated with, and, in part, due to oxidative stress. While occurrence of oxidative stress in lead-exposed animals and cultured endothelial cells has been well-established, direct and specific evidence on the type of the reactive oxygen species (ROS) produced by lead-exposed vascular cells is lacking and was investigated.
METHODS: Human coronary endothelial (EC) and vascular smooth muscle cells (VSMC) were incubated in appropriate culture media in the presence of either 1 ppm or 10 ppm lead acetate or sodium acetate (control) for 1 to 30 minutes or 60 hours. Productions of superoxide and hydrogen peroxide in the cell populations were determined by flow cytometry using hydroethidine and dihydrorhodamine, respectively. Data from a minimum of 10,000 cells were collected and analyzed using Cell Quest software. In addition, Cu Zn superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX), and NAD(P)H oxidase (gp91phox) were measured.
RESULTS: Short-term lead exposure resulted in a significant rise in both superoxide and hydrogen peroxide production by both EC and VSMC. After long-term exposure, detectable superoxide levels fell to near normal level, while hydrogen peroxide production remained high. This was associated with up-regulations of gp91phox, elevation of superoxide dismutase, reduction of VSMC catalase, and no change in GPX levels. Together, these events can account for the observed decline in superoxide and the rise in hydrogen peroxide following long-term lead exposure.
CONCLUSION: Lead exposure promotes generation of superoxide and hydrogen peroxide in human EC and VSMC. This phenomenon can potentially contribute to the pathogenesis of the lead-associated hypertension and cardiovascular disease, and points to the potential benefit of lowering lead burden in the exposed populations.
Author List
Ni Z, Hou S, Barton CH, Vaziri NDAuthor
Fang Yao Stephen Hou PhD, MB(ASCP)QCYM, MLS(ASCPi) Clinical Assistant Professor in the Biomedical Sciences Laboratory Programs department at University of Wisconsin - MilwaukeeMESH terms used to index this publication - Major topics in bold
CatalaseCells, Cultured
Coronary Vessels
Endothelium, Vascular
Glutathione Peroxidase
Humans
Hydrogen Peroxide
Lead
Membrane Glycoproteins
Muscle, Smooth, Vascular
NADPH Oxidase 2
NADPH Oxidases
Oxidative Stress
Superoxide Dismutase
Superoxides