Protein kinase B inhibits apoptosis induced by actinomycin D in ECV304 cells through phosphorylation of caspase 8.
Actinomycin D (act-D) anchors itself into DNA-base pairs by intercalation and thereby inhibits mRNA synthesis. It has been well established that act-D elicits apoptosis in various cell types involving endothelial cells. However, the regulatory mechanisms of actinomycin D-induced apoptotic cell death still remain unclear. Here, we investigated apoptotic cell death and its underlying regulatory mechanisms elicited by actinomycin D in ECV304. Act-D induced typical apoptotic features including chromatin condensation and translocation of phosphatidylserine. Since the phosphoinositide 3-OH kinase (PI3K)/protein kinase B (PKB) signaling pathway has been shown to prevent apoptosis in various cell types, it was of interest to determine if this pathway could protect against apoptosis induced by act-D. Inhibition of PI3K/PKB significantly increased act-D-induced apoptosis. Moreover, act-D-induced cell death was physiologically linked to PKB-mediated cell survival through caspase-8. These results suggest that cross-talk between the PKB and caspase-8 pathways may regulate the balance between cell survival and cell death in ECV304.
Shim
Donghwan
D
Division of Life Sciences, Chungbuk National University, Cheongju 361-763, Republic of Korea.
Kang
Hee Young
HY
Jeon
Byeong Wook
BW
Kang
Sang Sun
SS
Chang
Soo-Ik
SI
Kim
Hak Yong
HY
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D003609:Dactinomycin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases; D011500:Protein Synthesis Inhibitors; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D014471:Umbilical Veins / Q000187:drug effects / Q000502:physiology
D011500:Protein Synthesis Inhibitors; D011518:Proto-Oncogene Proteins; D003609:Dactinomycin; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases