Dynamic changes in Bach1 expression in the kidney of rhabdomyolysis-associated acute kidney injury

Masakazu Yamaoka, Hiroko Shimizu, Toru Takahashi, Emiko Omori, Hiroshi Morimatsu

Research output: Contribution to journalArticle

Abstract

Free heme, a pro-oxidant released from myoglobin, is thought to contribute to the pathogenesis of rhabdomyolysis-associated acute kidney injury (RM-AKI), because renal overexpression of heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, confers protection against RM-AKI. BTB and CNC homology 1 (Bach1) is a heme-responsive transcription factor that represses HO-1. Here, we examined the changes with time in the gene expression of Bach1, HO-1, and d-aminolevulinate synthase (ALAS1, a heme biosynthetic enzyme) in the rat kidney using an RM-AKI model induced by the injection of 50% glycerol (10 mL/kg body weight) into bilateral limbs. We also examined the protein expression of Bach1 in the nucleus and cytosol, and HO-1 in the rat kidney. Glycerol treatment induced significant elevation of serum creatinine kinase and aspartate aminotransferase levels followed by the marked elevation of serum blood urea nitrogen and creatinine levels, which caused serious damage to renal tubules. Following glycerol treatment, HO-1 mRNA and protein levels were significantly up-regulated, while ALAS1 mRNA expression was down-regulated, suggesting an increase in the free renal heme concentration. The Bach1 mRNA level was drastically increased 3 h after glycerol treatment, and the increased level was maintained for 12 h. Nuclear Bach1 protein levels were significantly decreased 3 h after treatment. Conversely, cytosolic Bach1 protein levels abruptly increased after 6 h. In conclusion, we demonstrate the dynamic changes in Bach1 expression in a rat model of RM-AKI. Our findings suggest that the increase in Bach1 mRNA and cytosolic Bach1 protein expression may reflect de novo Bach1 protein synthesis to compensate for the depletion of nuclear Bach1 protein caused by the induction of HO-1 by free heme.

Original languageEnglish
Article numbere0180934
JournalPLoS One
Volume12
Issue number7
DOIs
Publication statusPublished - Jul 1 2017

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rhabdomyolysis
heme oxygenase (biliverdin-producing)
Rhabdomyolysis
Heme Oxygenase-1
Acute Kidney Injury
heme
kidneys
Heme
Kidney
Glycerol
glycerol
Proteins
Rats
Messenger RNA
protein synthesis
blood serum
Creatinine
creatinine
5-aminolevulinate synthase
proteins

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Dynamic changes in Bach1 expression in the kidney of rhabdomyolysis-associated acute kidney injury. / Yamaoka, Masakazu; Shimizu, Hiroko; Takahashi, Toru; Omori, Emiko; Morimatsu, Hiroshi.

In: PLoS One, Vol. 12, No. 7, e0180934, 01.07.2017.

Research output: Contribution to journalArticle

Yamaoka, Masakazu ; Shimizu, Hiroko ; Takahashi, Toru ; Omori, Emiko ; Morimatsu, Hiroshi. / Dynamic changes in Bach1 expression in the kidney of rhabdomyolysis-associated acute kidney injury. In: PLoS One. 2017 ; Vol. 12, No. 7.
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