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Voltage-dependent Anion Channel-1 (VDAC-1) Contributes to ATP Release and Cell Volume Regulation in Murine Cells
| Content Provider | Scilit |
|---|---|
| Author | O'Neal, Wanda K. Okada, Seiko F. Huang, Pingbo Nicholas, Robert A. Ostrowski, Lawrence E. Craigen, William J. Lazarowski, Eduardo R. Boucher, Richard C. |
| Copyright Year | 2004 |
| Abstract | Extracellular ATP regulates several elements of the mucus clearance process important for pulmonary host defense. However, the mechanisms mediating ATP release onto airway surfaces remain unknown. Mitochondrial voltage-dependent anion channels (mt-VDACs) translocate a variety of metabolites, including ATP and ADP, across the mitochondrial outer membrane, and a plasmalemmal splice variant (pl-VDAC-1) has been proposed to mediate ATP translocation across the plasma membrane. We tested the involvement of VDAC-1 in ATP release in a series of studies in murine cells. First, the full-length coding sequence was cloned from a mouse airway epithelial cell line (MTE7b−) and transfected into NIH 3T3 cells, and pl-VDAC-1-transfected cells exhibited higher rates of ATP release in response to medium change compared with mock-transfected cells. Second, ATP release was compared in cells isolated from VDAC-1 knockout [VDAC-1 (−/−)] and wild-type (WT) mice. Fibroblasts from VDAC-1 (−/−) mice released less ATP than WT mice in response to a medium change. Well-differentiated cultures from nasal and tracheal epithelia of VDAC-1 (−/−) mice exhibited less ATP release in response to luminal hypotonic challenge than WT mice. Confocal microscopy studies revealed that cell volume acutely increased in airway epithelia from both VDAC-1 (−/−) and WT mice after luminal hypotonic challenge, but VDAC-1 (−/−) cells exhibited a slower regulatory volume decrease (RVD) than WT cells. Addition of ATP or apyrase to the luminal surface of VDAC-1 (−/−) or WT cultures with hypotonic challenge produced similar initial cell height responses and RVD kinetics in both cell types, suggesting that involvement of VDAC-1 in RVD is through ATP release. Taken together, these studies suggest that VDAC-1, directly or indirectly, contributes to ATP release from murine cells. However, the observation that VDAC-1 knockout cells released a significant amount of ATP suggests that other molecules also play a role in this function. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234005/pdf http://jgp.rupress.org/content/124/5/513.full.pdf |
| Ending Page | 526 |
| Page Count | 14 |
| Starting Page | 513 |
| DOI | 10.1085/jgp.200409154 |
| Journal | The Journal of general physiology |
| Issue Number | 5 |
| Volume Number | 124 |
| Language | English |
| Publisher | Rockefeller University Press |
| Publisher Date | 2004-10-11 |
| Access Restriction | Open |
| Subject Keyword | Voltage-dependent Anion Channel Atp Release Osmotic Cell Swelling Regulatory Volume Decrease Airway Epithelia Journal: The Journal of general physiology (Vol- 124, Issue- 5) |
| Content Type | Text |
