Induction of molecular chaperones in carbon tetrachloride–treated rat liver: implications in protection against liver damage

Abstract

Carbon tetrachloride (CCl 4 ) 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 CCl 4 -treated rats was analyzed. Messenger ribonucleic acids for all these chaperones were markedly induced 3-12 hours after CCl 4 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 CCl 4 -induced liver damage was analyzed. When chaperones were preinduced in the liver by heat treatment, increase in serum alanine aminotransferase activity after CCl 4 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 CCl 4 treatment. These results suggest that cytosolic chaperones of Hsp70 and DnaJ families or Hsp90 (or both) are induced in CCl 4 -treated rat liver to protect the hepatocytes from the damage being inflicted.

Effects of dietary bovine lactoferrin on growth, haemato-biochemical parameters, immune functions and tolerance to air exposure stress in the African cichlid Sciaenochromis fryeri

“…Japanese flounder fed diets supplemented with LF rather than LF-free ones reportedly showed significantly higher levels of heat shock proteins (HSP70s), which is regarded as a general primary cellular event in the liver tissue in response to stress (Iwama, Vijayan, Forsyth, & Ackerman, 1999;Yokoyama et al, 2005). HSP acts as a regulator of liver functioning under stressful conditions (Lee et al, 2004). Consequently, it is expected that higher levels of synthesized of orally administrated LF on liver functions (Burrin, Wang, Heath, & Dudley, 1996;Tsubota et al, 2008).…”

“Toxic memory” via chaperone modification is a potential mechanism for rapid mallory-denk body reinduction

“…33 Similar to DDC, the human MDB inducer ethanol leads to no or limited chaperone induction, 34,35 whereas liver chaperone levels are regularly elevated in multiple acute and chronic stress conditions. [36][37][38] Therefore, the low chaperone levels in DDC-fed or chronic alcohol-consuming individuals may facilitate aggregate formation by decreasing chaperone function (Fig. 3) and levels (Fig.…”

Semi-Quantitative Analyses of Hippocampal Heat Shock Protein-70 Expression Based on the Duration of Ischemia and the Volume of Cerebral Infarction in Mice

“…Yenari 24) suggested that the increased expression of HSP-70 is an indicator of cellular stress. HSP-70 expression is elevated predominantly in the ischemic penumbra area 17 , 18) , and deletion of the HSP-70 gene exacerbates apoptosis after focal cerebral ischemia in mice 7) . It has recently been demonstrated that HSP-70 protects the brain against ischemia via an anti-inflammatory mechanism 4) .…”