Zinc Supplementation with Polaprezinc Protects Mouse Hepatocytes against Acetaminophen-Induced Toxicity via Induction of Heat Shock Protein 70
Zinc Supplementation with Polaprezinc Protects Mouse Hepatocytes against Acetaminophen-Induced Toxicity via Induction of Heat Shock Protein 70
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DOI：
10.3164/jcbn.09-60
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发表时间：
2010-01-01
影响因子：
2.4
通讯作者：
Matsura, Tatsuya
中科院分区：
文献类型：
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作者：
Nishida, Tadashi;Ohata, Shuzo;Matsura, Tatsuya
Polaprezinc是一种由锌和L-肌肽组成的螯合物，临床上用作治疗胃溃疡的药物。研究表明，热休克蛋白（HSP）的诱导参与了波拉普嗪对胃粘膜损伤的保护作用。在本研究中，我们研究了聚普锌及其成分是否可以诱导 HSP70 并预防小鼠原代培养肝细胞中的对乙酰氨基酚 (APAP) 毒性。用100μM浓度的泊普嗪、硫酸锌或L-肌肽处理肝细胞9小时，然后暴露于10mM APAP。 Polaprezinc 或硫酸锌增加细胞 HSP70 表达。然而，L-肌肽对其没有影响。用 Polaprezine 或硫酸锌预处理细胞可显着抑制 APAP 处理后的细胞死亡以及细胞脂质过氧化。相反，用聚普锌预处理并不影响APAP后细胞内谷胱甘肽的减少。此外，用 HSP 抑制剂 KNK437 治疗可减弱 Polaprezinc 诱导的 HSP70 表达增加，并消除 Polaprezine 对 APAP 后细胞死亡的保护作用。这些结果表明，polaprezinc，特别是其锌成分，可诱导小鼠原代培养肝细胞中HSP70的表达，并抑制APAP治疗后的脂质过氧化，从而防止APAP毒性。
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 polaprezine 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 polaprezine, zinc sulfate or L-carnosine at the concentration of 100 mu M 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 polaprezine 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 polaprezine 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.