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In addition, copper is also involved in the binding of HIF-1α to the hypoxia response element (HRE) sequence of target genes, which requires the copper molecular chaperone CCS, and activates EMT-related genes such as snail family transcriptional repressor 1 (SNAIL1), twist-related protein 1 (TWIST1), snail family transcriptional repressor 2 (SNAIL2), zinc finger E-box-binding homeobox 1 (ZEB1), zinc finger E-box-binding homeobox 2 (ZEB2), and E12/E47 (101)
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Toxicants like chlorpromazine, phenothiazines, erythromycin salts and chenodeoxycholate have direct surfactant effects on the hepatocyte plasma membrane [58]
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