title: Enhanced transcription factor DNA binding and gene expression induced by arsenite or arsenate in renal slices.
abstract: Although the kidney represents a target for the accumulation and toxicity of arsenic, little is known about the molecular targets of arsenic in this organ. Therefore, these studies were designed to examine the molecular impact of arsenite [As(III)] and arsenate [As(V)] at low (nanomolar) concentrations. Precision-cut rabbit renal cortical slices were challenged with As(III) or As(V) for up to 8 h. Neither form of the metal induced overt cytotoxicity as assessed by intracellular K+ levels over this time period at concentrations from 0.01-10 microM. In addition, no alterations in the expression of Hsp 60, 70, or 90 were observed. However, induction of heme oxygenase-1 (Hsp 32) was seen following a 4-h challenge with As(III), but not with As(V). As(III) and As(V) induced DNA binding of AP-1 at 2- and 4-h exposure; following a 6-h exposure there was no difference. Although no alteration in the DNA binding activity of ATF-2 was induced by As(III) or As(V), both forms enhanced the DNA binding activity of Elk-1. Enhanced DNA binding activity of AP-1 and Elk-1 correlated with increased gene expression of c-fos, but not c-jun, at 2 h. c-myc gene expression was also induced by As(III) and As(V), albeit at a later time point (6 h). These results suggest that acute arsenic challenge, by either As(III) or As(V), is associated with discrete alterations in the activity of signaling pathways and gene expression in renal tissue.
authors.affiliation: Department of Anesthesiology, College of Medicine, University of Arizona, Tucson 85721, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Parrish
authors.forename: X H
authors.initials: XH
authors.lastname: Zheng
authors.forename: K D
authors.initials: KD
authors.lastname: Turney
authors.forename: H S
authors.initials: HS
authors.lastname: Younis
authors.forename: A J
authors.initials: AJ
authors.lastname: Gandolfi
mesh_terms: D000818:Animals; D001149:Arsenates / Q000633:toxicity; D020261:Arsenic Poisoning; D018053:Arsenites / Q000633:toxicity; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D018736:DNA Adducts / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004586:Electrophoresis; D015870:Gene Expression / Q000187:drug effects*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects*; D008297:Male; D011188:Potassium / Q000032:analysis; D011817:Rabbits; D013723:Teratogens / Q000633:toxicity; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D001149:Arsenates; D018053:Arsenites; D018736:DNA Adducts; D013723:Teratogens; D014157:Transcription Factors; C015001:arsenite; C025657:arsenic acid; D011188:Potassium