African Journal of
Pharmacy and Pharmacology

  • Abbreviation: Afr. J. Pharm. Pharmacol.
  • Language: English
  • ISSN: 1996-0816
  • DOI: 10.5897/AJPP
  • Start Year: 2007
  • Published Articles: 2298

Full Length Research Paper

A calpain inhibitor elevated expressions of NF-κB in atrial fibrillation canine atria

Hong-Jie Xue1, Zhi-Hua Gong1*, Yue Li1*, Yong-Tai Gong1, Li Sheng1, Guang-Zhong Liu1, Wei-Min Li1 and Song-Bin Fu2
1Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin, P. R. China. 2Department of Genetics, Harbin Medical University, Harbin, P. R. China.
Email: [email protected]

  •  Accepted: 22 March 2012
  •  Published: 29 April 2012

Abstract

This aim of this study is to observe the alterations of calpain proteolytic system and effect of a calpain I inhibitor on NF-κB expressions in rapid pacing canine atrial fibrillation (AF) models. Twenty-one dogs were divided equally into three groups: a sham operation group, a control AF group and a calpain inhibitor group. Rapid right atrium pacing at 600 beats per min was applied in the control AF group and the calpain inhibitor group. N-Acetyl-Leu-Leu-Met (1.0 mg/kg/day) was administered in the calpain inhibitor group for three weeks. The protein expressions of NF-κB, calpain I, calpain II and calpastatin were assessed by immunohistochemistry and gene amplification of NF-κB and calpain I were detected by quantitative real time polymerase chain reaction. The highest density of calpain I was shown in the control AF group (p < 0.01, vs. calpain inhibitor group and sham operation group). Protein expression of calpain II and calpastatin had no significant difference among the three groups. Gene amplification results of calpain I unveiled the most active transcription was in the calpain inhibitor group (p < 0.01, vs. control AF group and sham operation group). The mRNA expression of NF-κB were elevated in the calpain inhibitor group, the cycle of threshold means were (20.1±5.1), while were (33.4±6.1) and (30.4±5.8) in the sham operation group and control AF group, respectively. NF-κB protein expressions in calpain inhibitor group were positive, while were negative in the other two groups. In canine heart muscle cells, atrial fibrillation elevated calpain I gene transcription, promoted protein expression and enhanced protease activity. The calpain I inhibitor N-Acetyl-Leu-Leu-Met promoted NF-κB gene transcription and protein expressions in AF canine models.

 

Key words: Calpain I inhibitor, atrial fibrillation, NF-κB.