Wanitchakool, Podchanart and Ousingsawat, Jiraporn and Sirianant, Lalida and MacAulay, Nanna and Schreiber, Rainer and Kunzelmann, Karl (2016) Cl- channels in apoptosis. EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, 45 (7). pp. 599-610. ISSN 0175-7571, 1432-1017
Full text not available from this repository. (Request a copy)Abstract
A remarkable feature of apoptosis is the initial massive cell shrinkage, which requires opening of ion channels to allow release of K+, Cl-, and organic osmolytes to drive osmotic water movement and cell shrinkage. This article focuses on the role of the Cl- channels LRRC8, TMEM16/anoctamin, and cystic fibrosis transmembrane conductance regulator (CFTR) in cellular apoptosis. LRRC8A-E has been identified as a volume-regulated anion channel expressed in many cell types. It was shown to be required for regulatory and apoptotic volume decrease (RVD, AVD) in cultured cell lines. Its presence also determines sensitivity towards cytostatic drugs such as cisplatin. Recent data point to a molecular and functional relationship of LRRC8A and anoctamins (ANOs). ANO6, 9, and 10 (TMEM16F, J, and K) augment apoptotic Cl- currents and AVD, but it remains unclear whether these anoctamins operate as Cl- channels or as regulators of other apoptotic Cl- channels, such as LRRC8. CFTR has been known for its proapoptotic effects for some time, and this effect may be based on glutathione release from the cell and increase in cytosolic reactive oxygen species (ROS). Although we find that CFTR is activated by cell swelling, it is possible that CFTR serves RVD/AVD through accumulation of ROS and activation of independent membrane channels such as ANO6. Thus activation of ANO6 will support cell shrinkage and induce additional apoptotic events, such as membrane phospholipid scrambling.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | REGULATED ANION CHANNEL; TRANSMEMBRANE CONDUCTANCE REGULATOR; MUTANT CYSTIC-FIBROSIS; CELL-VOLUME REGULATION; CANCER-CELLS; ESSENTIAL COMPONENT; CHLORIDE CHANNEL; ANOCTAMIN 6; CISPLATIN RESISTANCE; OXIDATIVE STRESS; LRRC8A; Anoctamin; TMEM16A; TMEM16F; CFTR; Apoptosis; Volume regulation; RVD; Cell death; Chloride channel; Ca2+-activated chloride channels; TMEM16K; TMEM16J |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Apr 2019 08:00 |
| Last Modified: | 11 Apr 2019 08:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4233 |
Actions (login required)
 |
View Item |
