Low Zinc Ameliorated the Decrease in Intestinal Copper Level Induced by Low Dietary Copper: Involvement of...

Area of Science:

• Animal nutrition and metabolism
• Trace element interactions
• Molecular mechanisms of nutrient regulation

Background:

• Copper (Cu) and zinc (Zn) are essential trace elements for vertebrate health.
• Inadequate intake or imbalances can lead to adverse health effects.
• Interactions between trace elements are critical for maintaining homeostasis.

Purpose of the Study:

• To investigate if low dietary Zn can mitigate the negative effects of low dietary Cu on intestinal Cu levels.
• To elucidate the molecular mechanisms underlying this interaction.
• To explore the roles of Mtf-1 and Atp7a in Cu and Zn metabolism.

Main Methods:

• In vivo animal experiments and in vitro cell culture models were employed.
• Electrophoretic mobility shift assays and chromatin immunoprecipitation analyzed Mtf-1 and Atp7a interactions.
• Immunoprecipitation and dual-luciferase reporter assays assessed Mtf-1 SUMOylation and its effect on atp7a promoter activity.

Main Results:

• Low dietary Cu significantly increased Mtf-1 transcriptional regulation of the Atp7a promoter, causing intestinal Cu metabolism disorders.
• Supplementation with low Zn in a low Cu diet inhibited Mtf-1's regulation of the Atp7a promoter.
• This inhibition alleviated intestinal Cu metabolism disorders caused by low Cu.
• Mtf-1 SUMOylation, particularly with Sumo1, reduced Atp7a promoter activity.

Conclusions:

• Dietary low Zn alleviates low Cu-induced decreases in intestinal Cu levels.
• The mechanism involves the SUMOylated-Mtf-1 and the Mtf-1/Atp7a signaling axis.
• This highlights the crucial role of Zn in modulating Cu metabolism under deficiency conditions.