A novel function of BCL-2 overexpression in regulatory volume decrease. Enhancing swelling-activated Ca2+ entry and Cl- channel activity

Meng-Ru Shen, Tzi Peng Yang, Ming-Jer Tang

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27 Citations (Scopus)

Abstract

The cellular function of the oncogene bcl-2, a key regulator of apoptosis, is still debated. The goal of this study was to explore the relationship between BCL-2 overexpression and cell volume regulation by using two independent models, Madin-Darby canine kidney (MDCK) cells stably transfected with BCL-2 and MDCK clones with inducible BCL-2 expression by the lac operator/repressor. BCL-2 overexpression enhanced the capability of regulatory volume decrease (RVD), a cellular defensive process against hypotonic stress. In various clones of MDCK cells, hypotonic stress induced an outwardly rectified Cl- current that was significantly upregulated by BCL-2 overexpression. Other fundamental characteristics of this channel were similar among different MDCK clones, such as sensitivity to Cl- channel inhibitor, anion permeability, and time-dependent inactivation at more positive potential. Most importantly, BCL-2 overexpression up-regulates the swelling-activated Ca2+ transient that is a critical signaling for normal RVD and the activation of swelling-activated Cl- channel in MDCK cells. BCL-2 overexpression also enhances the capacitative Ca2+ entry that can be differentiated from the swelling-activated Ca2+ transient by kinetic analysis and sensitivity to Gd3+. Moreover, neutralization of endogenous BCL-2 by antibody blocks the normal RVD response and the activation of swelling-activated Cl- channel in human cervical cancer HT-3 cells. These results provide a new insight into the novel function of BCL-2 overexpression in the regulation of cell volume and ion flux.

Original languageEnglish
Pages (from-to)15592-15599
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number18
DOIs
Publication statusPublished - 2002 May 3

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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