Comparative 2D-electrophoretic mapping of human and rodent hepatic stress proteins as potential biomarkers.
Toxicologic studies in rodents demonstrate that two-dimensional polyacrylamide gel electrophoresis of proteins (2DE) is very useful in the detection and evaluation of chemical toxicity by providing information regarding cellular status at the molecular level. Identification of a set of specific biomarkers of exposure or effect, with a proclivity for both a particular rodent and human target tissue, is required for development of an electrophoretically based testing system. In this regard, stress proteins, such as the heat shock and glucose-regulated proteins (Hsp and Grp), are appropriate candidates. The present investigation was undertaken to identify these stress proteins on conventional two-dimensional electrophoretic gel patterns of human and rat liver homogenates. The following stress proteins were identified, their x, y coordinate positions mapped, and abundances determined, and these data statistically analyzed and compared: Hsp25, Hsp32, Hsp60, Hsc70, Hsp70, Hsp90, Grp75, Grp78, Grp94, protein disulfide isomerase (PDI), and ER-60. With the exception of Hsp25 and Hsp32, the stress proteins examined were constitutively expressed at detectable levels in both unstressed human and rat liver; in virtually identical patterns. Based on our results, the human hepatic 2DE stress protein pattern seems well-suited to toxicologic screening particularly in in vitro applications and via extrapolations from rodent exposures.
Witzmann
F A
FA
Dept. of Biology, IUPU-Columbus, Indiana 47203, USA.
Fultz
C
C
Lipscomb
J
J
D000818:Animals; D015415:Biomarkers; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000032:analysis*; D006801:Humans; D008099:Liver / Q000737:chemistry*; D008297:Male; D010449:Peptide Mapping; D051381:Rats; D011916:Rats, Inbred F344
D015415:Biomarkers; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins