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An ultraviolet-activated K+ channel mediates apoptosis of myeloblastic leukemia cells
1Department of Physiology and Biophysics, School of Medicine, Wright State University, Dayton, Ohio 45435, USA.
Abstract:
Exposure of mammalian cells to UV light causes initial changes in the cell membrane, induces phosphorylation and clustering of growth factor/cytokine receptors, and activates the Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) signaling pathway leading to programmed cell death (apoptosis). In this study, we found that an early event in the cell membrane of myeloblastic leukemia (ML-1) cells was the vigorous activation of the voltage-gated K+ channel by UV irradiation. The strong enhancement by UV irradiation of K+ channel activity in the cell membrane subsequently activated the JNK/SAPK signaling pathway and resulted in myeloblastic leukemia cell apoptosis. Suppression of UV-induced K+ channel activation with specific channel blockers prevented UV-induced apoptosis through inhibition of UV-induced activation of the proteins SEK (SPAK kinase) and JNK. However, suppression of K+ channel activity could not protect cells from etoposide-induced apoptosis, which bypasses the membrane event. Elimination of extracellular Ca2+ had no effect on the UV-induced and K+ channel-mediated JNK/SAPK activation. Thus, we have identified a novel mechanism in which activation of K+ channels by UV-irradiation upstream of SEK and SAPK/JNK mediates UV-induced myeloblastic cell apoptosis.
Insights
UV irradiation activates voltage-gated potassium (K+) channels in myeloblastic leukemia cells, initiating apoptosis. Blocking K+ channel activity prevents UV-induced programmed cell death by inhibiting stress-activated protein kinase pathways.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- UV radiation triggers cellular responses, including receptor clustering and stress-activated protein kinase (SAPK) pathway activation, leading to apoptosis.
- The precise early membrane events mediating UV-induced apoptosis in cancer cells remain incompletely understood.
Purpose of the Study:
- To elucidate the role of ion channels in UV-induced apoptosis of myeloblastic leukemia cells.
- To identify novel molecular mechanisms linking UV exposure to programmed cell death.
Main Methods:
- Utilized myeloblastic leukemia (ML-1) cell models.
- Investigated UV irradiation effects on cell membrane ion channel activity.
- Assessed activation of the Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) pathway.
- Employed specific ion channel blockers and examined apoptosis induction.
Main Results:
- UV irradiation vigorously activated voltage-gated potassium (K+) channels in ML-1 cell membranes.
- K+ channel activation by UV irradiation was essential for subsequent JNK/SAPK pathway activation and apoptosis.
- Inhibition of K+ channels blocked UV-induced apoptosis and JNK/SAPK activation.
- K+ channel activity was not involved in etoposide-induced apoptosis or UV-induced JNK/SAPK activation when extracellular calcium was absent.
Conclusions:
- UV irradiation initiates apoptosis in myeloblastic leukemia cells via early activation of voltage-gated K+ channels.
- K+ channel activation acts upstream of SEK and SAPK/JNK, mediating a novel pathway for UV-induced programmed cell death.
- Targeting K+ channels could offer a therapeutic strategy for UV-induced apoptosis in leukemia.