Deletion of metal transporter Zip14 (Slc39a14) produces skeletal muscle wasting, endotoxemia, Mef2c activation and induction of miR-675 and Hspb7.

Scientific Reports
Jinhee KimRobert J Cousins

Abstract

Skeletal muscle represents the largest pool of body zinc, however, little is known about muscle zinc homeostasis or muscle-specific zinc functions. Zip14 (Slc39a14) was the most highly expressed zinc transporter in skeletal muscle of mice in response to LPS-induced inflammation. We compared metabolic parameters of skeletal muscle from global Zip14 knockout (KO) and wild-type mice (WT). At basal steady state Zip14 KO mice exhibited a phenotype that included muscle wasting and metabolic endotoxemia. Microarray and qPCR analysis of gastrocnemius muscle RNA revealed that ablation of Zip14 produced increased muscle p-Mef2c, Hspb7 and miR-675-5p expression and increased p38 activation. ChIP assays showed enhanced binding of NF-[Formula: see text] to the Mef2c promoter. In contrast, LPS-induced systemic inflammation enhanced Zip14-dependent zinc uptake by muscle, increased expression of Atrogin1 and MuRF1 and markedly reduced MyoD. These signatures of muscle atrophy and cachexia were not influenced by Zip14 ablation, however. LPS-induced miR-675-3p and -5p expression was Zip14-dependent. Collectively, these results with an integrative model are consistent with a Zip14 function in skeletal muscle at steady state that supports myogenesi...Continue Reading

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Citations

Apr 4, 2021·International Journal of Molecular Sciences·Keisuke HitachiKunihiro Tsuchida
Apr 9, 2021·Biochemistry. Biokhimii︠a︡·Lydia K MuranovaNikolai B Gusev
May 21, 2021·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·Jingyun LiuQun Zuo

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Methods Mentioned

BETA
PCR
electrophoresis
ChIP
transfection
flame atomic absorption spectrophotometry
protein assay
immunoprecipitation
ELISA

Software Mentioned

JMP Pro13
Affymetrix Transcriptome Analysis Console
Prism
ImageJ
SAS

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