Disparity between ionic mediators of volume regulation and apoptosis in N1E 115 mouse neuroblastoma cells
In: Brain research, Jg. 943 (2002-07-09), Heft 2
Online
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Zugriff:
Cellular volume loss or shrinkage is a ubiquitous feature of apoptosis and thus may contribute to this form of degeneration. Chloride (Cl(-)) and potassium (K(+)) efflux has been shown to participate in volume regulation and several recent reports have implicated K(+) efflux in apoptotic neuronal death. Here pharmacological inhibitors of various K(+) and Cl(-) channels and transporters were used to decipher the relationship between cellular volume regulation and apoptosis. Following exposure to a hypotonic media, cells swell but over time gradually recover, returning to their original cell volume in a process known as regulatory volume decrease (RVD). RVD in N1E 115 neuroblastoma cells was monitored using time-lapse videomicroscopy, cell size and DNA degradation were followed using flow cytometry and fragmented apoptotic nuclei were visualized using Hoechst staining. RVD was blocked by high K(+), TEA and 4-AP (K(+) channel blockers), DIDS and niflumic acid but not SITS (Cl(-) channel blockers), ethacrynic acid (Cl(-) pump blocker), bumetanide (Na(+)/K(+)/Cl(-) cotransporter blocker) and furosemide (K(+)/Cl(-) cotransport blocker). In contrast, only DIDS and SITS (blockers of the Cl(-)/HCO(3) exchanger) inhibited apoptosis, suggesting that a common mechanistic link between RVD and apoptosis is the Cl(-)/HCO(3) exchanger. Thus, this study does not support the notion that K(+) channels are universal anti-apoptotic targets. Instead, the Cl(-)/HCO(3) exchanger may prove to be a viable target of therapeutic intervention for treating pathological apoptosis and neurodegeneration.
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Disparity between ionic mediators of volume regulation and apoptosis in N1E 115 mouse neuroblastoma cells
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Autor/in / Beteiligte Person: | Tauskela, Joseph S. ; O’Reilly, Natasha ; Xia, Zhenlei ; Small, Daniel L. ; Fiander, Hawley |
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Zeitschrift: | Brain research, Jg. 943 (2002-07-09), Heft 2 |
Veröffentlichung: | 2002 |
Medientyp: | unknown |
ISSN: | 0006-8993 (print) |
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