Mechanisms of chromium (VI)-induced apoptosis in anterior pituitary cells.
Hexavalent chromium (Cr (VI)) is a highly toxic metal. Exposure to Cr (VI) compounds may affect reproductive functions. Due to the importance of anterior pituitary hormones on reproductive physiology we have studied the effects of Cr (VI) on anterior pituitary. We previously demonstrated that, after in vivo Cr (VI) administration, Cr accumulates in the pituitary gland and affects prolactin secretion. In vitro, Cr (VI) causes apoptosis in anterior pituitary cells due to oxidative stress generation. To better understand the mechanisms involved in Cr (VI)-induced apoptosis we studied: (a) whether Cr (VI) affects the intracellular antioxidant response and (b) which of the apoptotic factors participates in Cr (VI) effect. Our results show that Cr (VI) treatment induces a decrease in catalase and glutathione peroxidase (GPx) activity but does not modify glutathione reductase (GR) activity. Cr (VI) exposure causes an increase of GSH levels. p53 and Bax mRNA are also upregulated by the metal. Pifithrin alpha, a p53 transcriptional inhibitor, increases Cr (VI) cytotoxicity, suggesting a role of p53 as a survival molecule. The antioxidant N-acetyl-cysteine (NAC) could prevent Bax mRNA increase and caspase 3 activation, confirming that Cr (VI)-induced apoptosis involves oxidative stress generation.
Departamento de Química Biológica, IQUIFIB, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, Buenos Aires, Argentina.
Fernanda A
FA
Quinteros
Leticia I
LI
Machiavelli
Eliana A
EA
Miler
Jimena P
JP
Cabilla
Beatriz H
BH
Duvilanski
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D002857:Chromium / Q000633:toxicity*; D017931:DNA Primers; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010903:Pituitary Gland, Anterior / Q000166:cytology* / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
D000975:Antioxidants; D017931:DNA Primers; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D002857:Chromium; D012313:RNA; D002374:Catalase; D020169:Caspases; C022616:thiazolyl blue; D000111:Acetylcysteine