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VDAC‐1 May Interact with CFTR to Impart Important Cellular Function in Mouse Heart
Author(s) -
Xiang Sunny Yang,
Schegg Kathleen,
Ye Linda L,
Hatton William J,
Duan Dayue
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a799-b
Subject(s) - cystic fibrosis transmembrane conductance regulator , voltage dependent anion channel , western blot , microbiology and biotechnology , chemistry , cardioprotection , transmembrane protein , blot , ion channel , membrane protein , myocyte , biology , biochemistry , medicine , membrane , ischemia , gene , bacterial outer membrane , receptor , escherichia coli
The cystic fibrosis transmembrane‐conductance regulator (CFTR) Cl − channels may play an important role in ischemic preconditioning (IPC)‐mediated cardioprotection in mouse heart. To investigate the mechanisms for the role of CFTR in IPC we used proteomic approaches to analyze changes in the protein expression profiles of both plasma membrane (PM) and mitochondrial (MT) compartments caused by CFTR gene knockout. Proteins from heart tissue (10 hearts pooled as one sample) of either wild‐type (FVB/NJ) or CFTR −/− (FABPCFTR) mice were isolated, purified, and fractionated. Marker enzyme assays demonstrated a 1.74‐fold enrichment of PM in the PM fractions and a 4.4‐fold enrichment of MT in MT fractions, and a strong reduction of other compartments. Proteomic analysis (2D‐PAGE, MALDI‐TOF/TOF mass spectrometry) unambiguously identified a significant (40%) decrease in the expression of the voltage‐dependent anion channel 1 (VDAC‐1) in cardiac PM proteins of the CFTR −/− mice. Immunocytochemistry confirmed VDAC‐1 expression in PM of cardiac myocytes. Western blots on both 2D‐PAGEs and 1D gels further confirmed the reduced expression of VDAC‐1 in PM of CFTR −/− mouse heart. These results strongly suggest that VDAC‐1 may be an important component of the CFTR subproteome and may interact with CFTR to impart orchestrated functions in IPC‐mediated cardioprotection. (Supported by NCRR at NIH P20 RR15581 and NIH R01 HL63914)