Anti-oxidative response of carbonic anhydrase III in skeletal muscle

Un Jin P. Zimmerman*, Ping Wang, Xiangming Zhang, Sasha Bogdanovich, Robert E. Forster

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


We propose that carbonic anhydrase III (CAIII) functions as an anti-oxidant agent in skeletal muscle. To explore this hypothesis, we analyzed the gene expression profile of skeletal muscle in mice deficient in CAIII gene utilizing the murine genome U74Av2 set microarray. Pairwise comparison between CAIII knockout mice and their wild-type littermates revealed that more than 500 of 12,000 genes in the array showed an altered level of transcription. Of particular note were transcriptional alterations among genes associated with the glutathione redox cycle, suggesting a possible involvement of CAIII in the glutathione-mediated anti-oxidant activity. We therefore investigated S-glutathiolation and irreversible oxidation of the 2 reactive sulfhyryls of CAIII in skeletal muscle under oxidative stresses of ischemia, or exhaustive exercise. Analysis by isoelectric focusing followed by Western blot revealed that the two sulfhydryls were differentially and progressively oxidized. Brief ischemia of 10-20 min provoked partial (one of the suflhydryls) modification of CAIII via reversible S-glutathiolation. Protracted 60 min ischemia yielded equal amounts of both partially and completely (both sulfhydryls) modified CAIII due to irreversible oxidization. Twenty minutes of repetitive electrical stimulation, simulating exhaustive exercise, produced a mixed yield: partial modification by reversible S-glutathiolation and complete modification by irreversible oxidation. Thus CAIII responds to oxidative stress with a distinctive sulfhydryl oxidation patterns reflecting duration and severity that may prove sensitive indices of extent and type of damage in muscle injury.

Original languageEnglish (US)
Pages (from-to)343-347
Number of pages5
JournalIUBMB Life
Issue number6
StatePublished - Jun 2004


  • CAIII knockout mice
  • Exhaustive exercise
  • Irreversible oxidation
  • Ischemia
  • S-glutathiolation
  • Transcription profile

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Clinical Biochemistry
  • Cell Biology


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