Effects of selenocystine on lead-exposed Chinese hamster ovary (CHO) and PC-12 cells.
Lead is a pervasive environmental toxin that affects multiple organ systems, including the nervous, renal, reproductive, and hematological systems. Even though it is probably the most studied toxic metal, some of the symptoms of lead toxicity still cannot be explained by known molecular mechanisms. Therefore, lead-induced oxidative stress has recently started to gain attention. This in vitro study confirms the existence of oxidative stress due to lead exposure. Administration of lead acetate (PbA) to cultures of Chinese hamster ovary cells (CHO) had a concentration-dependent inhibitory effect on colony formation and cell proliferation. This inhibition was eliminated by 5 microM selenocystine (SeCys). In order to evaluate the nature of SeCys's effect, we measured glutathione (GSH), its oxidized form glutathione disulfide (GSSG), malondialdehyde (MDA), catalase, and GSH peroxidase (GPx) activities in lead-exposed CHO cells both in the presence and absence of SeCys. Increases in MDA, catalase, and GPx activities were observed in cultures that received only PbA, but supplementation with SeCys returned these measures to pretreatment levels. The ratio of GSH to GSSG increased in lead-exposed cells incubated in SeCys-enhanced media but declined in cultures treated with PbA only. In order to determine whether SeCys also reverses lead-induced neurotoxicity, a neuronal cell line, PC-12 cells, was used. Lead's inhibition on neurite formation was significantly eliminated by SeCys in PC-12 cells. Our results suggest that SeCys can confer protection against lead-induced toxicity in CHO cells and neurotoxicity in PC-12 cells.
Aykin-Burns
Nukhet
N
Department of Chemistry, University of Missouri-Rolla, 1870 Miner Circle, 142 Schrenk Hall, Rolla, MO 65409, USA.
Ercal
Nuran
N
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016466:CHO Cells; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003412:Cricetulus; D003553:Cystine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009942:Organometallic Compounds / Q000633:toxicity*; D016566:Organoselenium Compounds / Q000494:pharmacology*; D016716:PC12 Cells; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats
D009942:Organometallic Compounds; D016566:Organoselenium Compounds; C009226:selenocystine; D003553:Cystine; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D011493:Protein Kinase C; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C008261:lead acetate; D019803:Glutathione Disulfide