Valinomycin-induced apoptosis in Chinese hamster ovary cells.
Accumulating evidence endorses that excessive K(+) efflux is an ionic mechanism underlying apoptosis both in neuronal and non-neuronal cells. K(+) channels play important roles in mediating the pro-apoptotic K(+) efflux. Chinese hamster ovary (CHO) cells have been widely used for gene transfection experiments. These cells lack detectable endogenous voltage-gated K(+) channels. We were interested in knowing whether the absence of endogenous K(+) channels would render wild-type CHO cells more resistant to apoptotic death. We also wished to determine if direct stimulation of K(+) efflux would trigger apoptosis in these cells. Exposing CHO cells to hypoxia (1% O(2)) or to a typical apoptotic insult of serum deprivation for up to 24h did not affect cell survival. On the other hand, the K(+) ionophore valinomycin caused substantial cell death within 12h of its application. Valinomycin-treated CHO cells underwent several apoptotic events, including phosphatidylserine (PS) membrane translocation, caspase-3 activation, and mitochondrial membrane depolarization during the first few hours of exposure. Reducing K(+) efflux by elevating extracellular K(+) concentrations noticeably attenuated valinomycin-induced cell death. This study reinforces a K(+) efflux-mediated apoptotic mechanism in CHO cells and may help to explain the unique feature of their higher tolerance to apoptosis.
Abdalah
Rany
R
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, United States.
Wei
Ling
L
Francis
Kevin
K
Yu
Shan Ping
SP
D000818:Animals; D017209:Apoptosis; D016466:CHO Cells; D002414:Cations, Monovalent; D015687:Cell Hypoxia; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D016895:Culture Media, Serum-Free; D007476:Ionophores / Q000494:pharmacology*; D051336:Mitochondrial Membranes / Q000502:physiology; D010718:Phosphatidylserines / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D014634:Valinomycin / Q000494:pharmacology*
D002414:Cations, Monovalent; D016895:Culture Media, Serum-Free; D007476:Ionophores; D010718:Phosphatidylserines; D014634:Valinomycin; D011188:Potassium