Abstract
Zinc is an essential trace element and plays critical roles in cellular integrity and biological functions. Excess copper induced both oxidative stress and endoplasmic reticulum (ER) stress in liver-derived cultured cells. Excess copper also induced impairment of autophagic flux at the step of autophagosome–lysosome fusion, as well as Mallory–Denk body (MDB)-like inclusion body formation. Zinc ameliorated excess copper-induced impairment of autophagic flux and MDB-like inclusion body formation via the maintenance of ER homeostasis. Furthermore, zinc also ameliorated free fatty acid-induced impairment of autophagic flux. These results indicate that zinc may be able to protect hepatocytes from various ER stress-related conditions.
Highlights
Zinc is an essential trace element and plays critical roles in cellular integrity and various biological functions
To clarify whether the ameliorative effect of zinc acetate on excess copper-induced endoplasmic reticulum (ER) stress was accompanied by a reduction of abnormal proteins, we monitored the levels of ubiquitinated proteins by immunoblotting analysis
We found that the level of ubiquitinated proteins increased in the excess copper-treated cultured hepatocytes, and that this effect was ameliorated in the presence of zinc acetate (Figure 1B)
Summary
Zinc is an essential trace element and plays critical roles in cellular integrity and various biological functions. Conditioned zinc deficiency is present in many chronic diseases such as rheumatoid arthritis, cancers, and liver diseases, which are mainly associated with chronic inflammation and oxidative stress [3,4]. Zinc acetate has been commonly used to treat patients with Wilson disease because it inhibits absorption of copper from the intestinal epithelia [11]. We have previously reported that excess copper induced endoplasmic reticulum (ER) stress as well as oxidative stress, contributing to disease progression in Wilson disease [12]. We have confirmed that zinc acetate dampened ER stress and hepatotoxicity, including DNA damage and apoptosis induced by excess copper. We speculate that zinc acetate may play an important role in the protection of ER homeostasis in conditions of other liver diseases
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