Toxicant-induced alterations in two-dimensional electrophoretic patterns of hepatic and renal stress proteins.
Recent studies in this laboratory and by others suggest that two-dimensional polyacrylamide gel electrophoresis of proteins (2-DE) possesses significant utility in the detection of chemical toxicity and in providing information regarding toxic mechanism. After having identified a set of specific heat-shock and glucose-regulated proteins whose expression in rodent liver and kidney is highly conserved and constitutive, we compared the effect of in vivo exposure to perfluoro-n-octanoic acid and perfluoro-n-decanoic acid on their expression. The following stress proteins were identified, their x, y coordinate positions mapped, and abundance statistically analyzed and compared: hsp32, hsp60, hsc70, hsp70, hsp90, grp75, grp94, protein disulfide isomerase (PDI), and ER60. We report here that the stress response to perfluorocarboxylic acids is tissue-, toxicant-, and stress protein class-specific and dose-related. Furthermore, because nearly all of the proteins studied were constitutively expressed at detectable levels in both liver and kidney, the 2-DE stress protein pattern may be suitable to future toxicologic screening applications.
Witzmann
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FA
Molecular Anatomy Laboratory, Indiana University-Purdue University, Columbus, USA. witzmann@molan1.iupui.edu
Fultz
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CD
Lipscomb
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JC
D000818:Animals; D002210:Caprylates / Q000633:toxicity*; D003652:Decanoic Acids / Q000633:toxicity*; D015180:Electrophoresis, Gel, Two-Dimensional; D005466:Fluorocarbons / Q000633:toxicity*; D006360:Heat-Shock Proteins / Q000032:analysis* / Q000187:drug effects; D007668:Kidney / Q000737:chemistry*; D008099:Liver / Q000737:chemistry*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D002210:Caprylates; D003652:Decanoic Acids; D005466:Fluorocarbons; D006360:Heat-Shock Proteins; C036567:perfluorodecanoic acid; C023036:perfluorooctanoic acid