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In addition, copper is also involved in the binding of HIF-1 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)

a - f , Treatment of C57BL/6 J DIO mice with once-daily subcutaneous (s.c.) injections of 900 nmol kg 1 MK-801 (n = 8 mice and n = 4 cages), 1800 nmol kg 1 MK-801 (n = 6 mice and n = 3 cages) or vehicle (isotonic saline, n = 7 mice and n = 3 cages) over 7 days