Induction of molecular chaperones in carbon tetrachloride-treated rat liver: implications in protection against liver damage.
Carbon tetrachloride (CCl4) induces liver damage, apparently through the formation of free-radical metabolites. Molecular chaperones such as heat shock protein (Hsp) of 70 kDa have been found to protect cells from various stresses. We previously found that cytosolic chaperone pairs of the Hsp70 family and their DnaJ homolog cochaperones prevent nitric oxide-mediated apoptosis and heat-induced cell death. Expression of cytosolic chaperones, including Hsp70; heat shock cognate (Hsc) 70; and DnaJ homologs dj1 (DjB1/Hsp40/hdj-1), dj2 (DjA1/HSDJ/hdj-2), dj3 (DjA2), and dj4 (DjA4), in the liver of CCl4-treated rats was analyzed. Messenger ribonucleic acids for all these chaperones were markedly induced 3-12 hours after CCl4 treatment with a maximum at 6 hours. Hsp70 and dj1 proteins were markedly induced at 6-24 hours with a maximum at 12 hours, whereas dj2 and dj4 were moderately induced at around 12 hours. Hsc70 was weakly induced after treatment, and dj3 was little induced. To better understand the significance of the induction of chaperones, the effect of preinduction of chaperones on CCl4-induced liver damage was analyzed. When chaperones were preinduced in the liver by heat treatment, increase in serum alanine aminotransferase activity after CCl4 treatment was significantly attenuated. Hsp90, another major cytosolic chaperone, also was induced by heat treatment. On the other hand, Mn- and Cu/Zn-superoxide dismutase were not induced by heat treatment or by CCl4 treatment. These results suggest that cytosolic chaperones of Hsp70 and DnaJ families or Hsp90 (or both) are induced in CCl4-treated rat liver to protect the hepatocytes from the damage being inflicted.
Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto 860-8556, Japan.
Kwang-Jong
KJ
Lee
Kazutoyo
K
Terada
Seiichi
S
Oyadomari
Yukihiro
Y
Inomata
Masataka
M
Mori
Tomomi
T
Gotoh
D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000818:Animals; D001123:Argininosuccinate Lyase / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D002251:Carbon Tetrachloride / Q000494:pharmacology* / Q000633:toxicity; D015870:Gene Expression / Q000187:drug effects*; D050883:HSC70 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins; D006979:Hyperthermia, Induced; D007700:Kinetics; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D050883:HSC70 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C494373:Hspa8 protein, rat; D018832:Molecular Chaperones; D002251:Carbon Tetrachloride; D013482:Superoxide Dismutase; D000410:Alanine Transaminase; D001123:Argininosuccinate Lyase