The protective role of NF-kappaB and AP-1 in arsenite-induced apoptosis in aortic endothelial cells.
Arsenite (NaAsO(2)) has been shown to produce vascular dysfunction in many studies. Arsenite-induced damage to vascular endothelial cells represents one of the possible mechanisms causing leakage of the vascular endothelial barrier. To explore arsenite-induced vascular endothelial damage, we used primary porcine aortic endothelial cells (PAECs) as an in vitro system to test the effects of arsenite on signal transduction pathways and apoptosis. Here we demonstrated that arsenite exposure induced apoptosis accompanied by the occurrence of apoptotic signals including degradation of poly(ADP-ribose) polymerase (PARP) and CPP32 (cleavage/activation) and DNA ladder formation. By using the luciferase reporter assay, we demonstrated that arsenite exposure differentially activated two redox-sensitive transcription factors, NF-kappaB and AP-1. Lower levels of arsenite exposure (25 microM NaAsO(2), 24 h) induced co-activation of NF-kappaB and AP-1, accompanied by 9% total apoptosis. In contrast, higher levels of arsenite exposure (40 microM NaAsO(2), 24 h) induced higher levels of AP-1 activation, accompanied by 45% total apoptosis. Blockade of NF-kappaB or JNK activity further enhanced arsenite-induced apoptosis. Upregulation of JNK activity showed no effect on arsenite-induced apoptosis. Based on these data, we propose that activation of redox-sensitive transcription factors, NF-kappaB and AP-1, plays a very important role in the protection of PAECs from arsenite-induced apoptosis.
Tsou
Tsui-Chun
TC
Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Medical Research Building/Room 108, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan, Republic of China. tctsou@nhri.org.tw
Tsai
Feng-Yuan
FY
Wu
Meng Chan
MC
Chang
Louis W
LW
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology*; D017209:Apoptosis / Q000187:drug effects*; D018053:Arsenites / Q000633:toxicity*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine; D018808:Transcription Factor AP-1 / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology
D018053:Arsenites; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C015001:arsenite