A role of reactive oxygen species in apoptotic activation of volume-sensitive Cl- channel Export

@article{citeulike:3859465, abstract = {10.1073/pnas.0401604101 Apoptotic volume decrease is a pivotal event triggering a cell to undergo apoptosis and is induced by ionic effluxes resulting mainly from increased K and Cl conductances. Here, we demonstrate that in human epithelia HeLa cells both mitochondrion- and death receptor-mediated apoptosis inducers [staurosporine and Fas ligand or tumor necrosis factor (TNF)-α] rapidly activate Cl currents that show properties phenotypical of volume-sensitive outwardly rectifying Cl channel currents, including outward rectification, voltage-dependent inactivation gating at large positive potentials, inhibition by osmotic shrinkage, sensitivity to classic Cl channel blockers, and dependence on cytosolic ATP. Staurosporine, but not Fas ligand or TNF-α, rapidly (within 30 min) increased the intracellular level of reactive oxygen species (ROS). A ROS scavenger and an NAD(P)H oxidase inhibitor blocked the current activation by staurosporine but not by Fas ligand or TNF-α. A ROS scavenger also inhibited apoptotic volume decrease, caspase-3 activation, and apoptotic cell death induced by staurosporine. Thus, it is concluded that an apoptosis-triggering anion conductance is carried by the volume-sensitive outwardly rectifying Cl channel and that the channel activation on apoptotic stimulation with staurosporine, but not with Fas ligand or TNF-α, is mediated by ROS.}, author = {Shimizu, Takahiro and Numata, Tomohiro and Okada, Yasunobu}, citeulike-article-id = {3859465}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0401604101}, citeulike-linkout-1 = {http://www.pnas.org/content/101/17/6770.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/101/17/6770.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/15096609}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=15096609}, day = {27}, doi = {10.1073/pnas.0401604101}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {dpaper}, month = {April}, number = {17}, pages = {6770--6773}, posted-at = {2009-01-08 07:25:07}, priority = {2}, title = {A role of reactive oxygen species in apoptotic activation of volume-sensitive Cl- channel}, url = {http://dx.doi.org/10.1073/pnas.0401604101}, volume = {101}, year = {2004} }

TY - JOUR ID - citeulike:3859465 L3 - citeulike-article-id:3859465 N2 - 10.1073/pnas.0401604101 Apoptotic volume decrease is a pivotal event triggering a cell to undergo apoptosis and is induced by ionic effluxes resulting mainly from increased K and Cl conductances. Here, we demonstrate that in human epithelia HeLa cells both mitochondrion- and death receptor-mediated apoptosis inducers [staurosporine and Fas ligand or tumor necrosis factor (TNF)-α] rapidly activate Cl currents that show properties phenotypical of volume-sensitive outwardly rectifying Cl channel currents, including outward rectification, voltage-dependent inactivation gating at large positive potentials, inhibition by osmotic shrinkage, sensitivity to classic Cl channel blockers, and dependence on cytosolic ATP. Staurosporine, but not Fas ligand or TNF-α, rapidly (within 30 min) increased the intracellular level of reactive oxygen species (ROS). A ROS scavenger and an NAD(P)H oxidase inhibitor blocked the current activation by staurosporine but not by Fas ligand or TNF-α. A ROS scavenger also inhibited apoptotic volume decrease, caspase-3 activation, and apoptotic cell death induced by staurosporine. Thus, it is concluded that an apoptosis-triggering anion conductance is carried by the volume-sensitive outwardly rectifying Cl channel and that the channel activation on apoptotic stimulation with staurosporine, but not with Fas ligand or TNF-α, is mediated by ROS. IS - 17 JF - Proceedings of the National Academy of Sciences of the United States of America EP - 6773 TI - A role of reactive oxygen species in apoptotic activation of volume-sensitive Cl- channel VL - 101 SP - 6770 KW - dpaper AU - Shimizu, Takahiro AU - Numata, Tomohiro AU - Okada, Yasunobu PY - 2004/04/27/ UR - http://dx.doi.org/10.1073/pnas.0401604101 ER -