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Zinc Supplementation with Polaprezinc Protects Mouse Hepatocytes against Acetaminophen-Induced Toxicity via Induction of Heat Shock Protein 70.

Nishida T, Ohata S, Kusumoto C, Mochida S, Nakada J, Inagaki Y, Ohta Y, Matsura T - J Clin Biochem Nutr (2009)

Bottom Line: Pretreatment of the cells with polaprezinc or zinc sulfate significantly suppressed cell death as well as cellular lipid peroxidation after APAP treatment.In contrast, pretreatment with polaprezinc did not affect decrease in intracellular glutathione after APAP.Furthermore, treatment with KNK437, an HSP inhibitor, attenuated increase in HSP70 expression induced by polaprezinc, and abolished protective effect of polaprezinc on cell death after APAP.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.

ABSTRACT
Polaprezinc, a chelate compound consisting of zinc and l-carnosine, is clinically used as a medicine for gastric ulcers. It has been shown that induction of heat shock protein (HSP) is involved in protective effects of polaprezinc against gastric mucosal injury. In the present study, we investigated whether polaprezinc and its components could induce HSP70 and prevent acetaminophen (APAP) toxicity in mouse primary cultured hepatocytes. Hepatocytes were treated with polaprezinc, zinc sulfate or l-carnosine at the concentration of 100 microM for 9 h, and then exposed to 10 mM APAP. Polaprezinc or zinc sulfate increased cellular HSP70 expression. However, l-carnosine had no influence on it. Pretreatment of the cells with polaprezinc or zinc sulfate significantly suppressed cell death as well as cellular lipid peroxidation after APAP treatment. In contrast, pretreatment with polaprezinc did not affect decrease in intracellular glutathione after APAP. Furthermore, treatment with KNK437, an HSP inhibitor, attenuated increase in HSP70 expression induced by polaprezinc, and abolished protective effect of polaprezinc on cell death after APAP. These results suggested that polaprezinc, in particular its zinc component, induces HSP70 expression in mouse primary cultured hepatocytes, and inhibits lipid peroxidation after APAP treatment, resulting in protection against APAP toxicity.

No MeSH data available.


Related in: MedlinePlus

Effect of polaprezinc, zinc sulfate or l-carnosine on HSP70 expression. HSP70 expression was analyzed by Western blot as described in materials and methods. (A) Time course of the expression of HSP70 after polaprezinc treatment. Cells were incubated in the presence of 100 µM polaprezinc for 0, 3, 6 or 9 h. (B) HSP70 expression 9 h after treatment with polaprezinc, zinc sulfate or l-carnosine at a concentration of 100 µM. Western blots were quantified with NIH Image. The data are expressed as means ± SE of 3 separate experiments. PZ; polaprezinc, ZS; zinc sulfate, LC; l-carnosine. **p<0.01 vs initial (0 h) time point (in A); ##p<0.01 vs control (in B).
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Figure 1: Effect of polaprezinc, zinc sulfate or l-carnosine on HSP70 expression. HSP70 expression was analyzed by Western blot as described in materials and methods. (A) Time course of the expression of HSP70 after polaprezinc treatment. Cells were incubated in the presence of 100 µM polaprezinc for 0, 3, 6 or 9 h. (B) HSP70 expression 9 h after treatment with polaprezinc, zinc sulfate or l-carnosine at a concentration of 100 µM. Western blots were quantified with NIH Image. The data are expressed as means ± SE of 3 separate experiments. PZ; polaprezinc, ZS; zinc sulfate, LC; l-carnosine. **p<0.01 vs initial (0 h) time point (in A); ##p<0.01 vs control (in B).

Mentions: Induction of HSP70 expression in mouse primary cultured hepatocytes after polaprezinc treatment was assessed by Western Blotting analysis. Cells were treated with polaprezinc and harvested after 3, 6 or 9 h. The expression of HSP70 increased in a time-dependent manner and HSP70 content was increased 3.9-fold of control level at 9 h after polaprezinc (Fig. 1A). We also examined whether zinc sulfate or l-carnosine, polaprezinc components, induces HSP70. Treatment with zinc sulfate increased HSP70 to 6.4-fold of control level, while l-carnosine treatment did not enhance HSP70 expression (Fig. 1B).


Zinc Supplementation with Polaprezinc Protects Mouse Hepatocytes against Acetaminophen-Induced Toxicity via Induction of Heat Shock Protein 70.

Nishida T, Ohata S, Kusumoto C, Mochida S, Nakada J, Inagaki Y, Ohta Y, Matsura T - J Clin Biochem Nutr (2009)

Effect of polaprezinc, zinc sulfate or l-carnosine on HSP70 expression. HSP70 expression was analyzed by Western blot as described in materials and methods. (A) Time course of the expression of HSP70 after polaprezinc treatment. Cells were incubated in the presence of 100 µM polaprezinc for 0, 3, 6 or 9 h. (B) HSP70 expression 9 h after treatment with polaprezinc, zinc sulfate or l-carnosine at a concentration of 100 µM. Western blots were quantified with NIH Image. The data are expressed as means ± SE of 3 separate experiments. PZ; polaprezinc, ZS; zinc sulfate, LC; l-carnosine. **p<0.01 vs initial (0 h) time point (in A); ##p<0.01 vs control (in B).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2803132&req=5

Figure 1: Effect of polaprezinc, zinc sulfate or l-carnosine on HSP70 expression. HSP70 expression was analyzed by Western blot as described in materials and methods. (A) Time course of the expression of HSP70 after polaprezinc treatment. Cells were incubated in the presence of 100 µM polaprezinc for 0, 3, 6 or 9 h. (B) HSP70 expression 9 h after treatment with polaprezinc, zinc sulfate or l-carnosine at a concentration of 100 µM. Western blots were quantified with NIH Image. The data are expressed as means ± SE of 3 separate experiments. PZ; polaprezinc, ZS; zinc sulfate, LC; l-carnosine. **p<0.01 vs initial (0 h) time point (in A); ##p<0.01 vs control (in B).
Mentions: Induction of HSP70 expression in mouse primary cultured hepatocytes after polaprezinc treatment was assessed by Western Blotting analysis. Cells were treated with polaprezinc and harvested after 3, 6 or 9 h. The expression of HSP70 increased in a time-dependent manner and HSP70 content was increased 3.9-fold of control level at 9 h after polaprezinc (Fig. 1A). We also examined whether zinc sulfate or l-carnosine, polaprezinc components, induces HSP70. Treatment with zinc sulfate increased HSP70 to 6.4-fold of control level, while l-carnosine treatment did not enhance HSP70 expression (Fig. 1B).

Bottom Line: Pretreatment of the cells with polaprezinc or zinc sulfate significantly suppressed cell death as well as cellular lipid peroxidation after APAP treatment.In contrast, pretreatment with polaprezinc did not affect decrease in intracellular glutathione after APAP.Furthermore, treatment with KNK437, an HSP inhibitor, attenuated increase in HSP70 expression induced by polaprezinc, and abolished protective effect of polaprezinc on cell death after APAP.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.

ABSTRACT
Polaprezinc, a chelate compound consisting of zinc and l-carnosine, is clinically used as a medicine for gastric ulcers. It has been shown that induction of heat shock protein (HSP) is involved in protective effects of polaprezinc against gastric mucosal injury. In the present study, we investigated whether polaprezinc and its components could induce HSP70 and prevent acetaminophen (APAP) toxicity in mouse primary cultured hepatocytes. Hepatocytes were treated with polaprezinc, zinc sulfate or l-carnosine at the concentration of 100 microM for 9 h, and then exposed to 10 mM APAP. Polaprezinc or zinc sulfate increased cellular HSP70 expression. However, l-carnosine had no influence on it. Pretreatment of the cells with polaprezinc or zinc sulfate significantly suppressed cell death as well as cellular lipid peroxidation after APAP treatment. In contrast, pretreatment with polaprezinc did not affect decrease in intracellular glutathione after APAP. Furthermore, treatment with KNK437, an HSP inhibitor, attenuated increase in HSP70 expression induced by polaprezinc, and abolished protective effect of polaprezinc on cell death after APAP. These results suggested that polaprezinc, in particular its zinc component, induces HSP70 expression in mouse primary cultured hepatocytes, and inhibits lipid peroxidation after APAP treatment, resulting in protection against APAP toxicity.

No MeSH data available.


Related in: MedlinePlus