NF-κB signaling maintains the survival of cadmium-exposed human renal glomerular endothelial cells.
The kidney is one of the primary organs targeted by cadmium (Cd), a widely distributed environmental pollutant. The glomerular endothelium is the major component of the glomerular filtration barrier. However, the effects of Cd on glomerular endothelial cells remain largely unknown. For this purpose, we aimed to determine the effects of low dose Cd on the survival of human renal glomerular endothelial cells (HRGECs). Cultured HRGECs were exposed to 4 µM cadmium chloride (CdCl2) and examined at different time-points. We found that Cd activates the nuclear factor-κB (NF-κB) pathway without inducing the apoptosis of HRGECs. Pre-treating the cells with pyrrolidine dithiocarbamate (PDTC), a potent NF-κB inhibitor, prior to Cd exposure triggered extensive cell death (73.5%). In addition, Cd activates the c-Jun N-terminal kinase (JNK) pathway, and inhibition of the NF-κB pathway significantly elevates Cd-induced JNK phosphorylation in HRGECs (p<0.01). The combination treatment of PDTC and SP600125, a JNK pathway inhibitor, increased the survival of Cd-stimulated HRGECs compared with those cells treated with PDTC alone (p<0.05). Taken together, these findings demonstrate that the NF-κB pathway plays an essential role in maintaining the survival of Cd-exposed HRGECs.
Department of Cardiovascular Medicine, Xintai City People's Hospital, Xintai Hospital Affiliated to Taishan Medical University, Xintai, Shandong 271200, P.R. China.
Hongyan
H
Zhang
Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
Liqun
L
Li
Weifang Medical College, Weifang, Shandong 261031, P.R. China.
Yifan
Y
Wang
Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
Fengyun
F
Dong
Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
Xiaocui
X
Chen
Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
Fuhong
F
Liu
Department of Nephrology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
Dongmei
D
Xu
Department of Pharmacology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
Fan
F
Yi
Department of Biology, Trent University, Peterborough, ON K9L 0G2, Canada.
Carolyn M
CM
Kapron
Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
Ju
J
Liu
D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002104:Cadmium / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007678:Kidney Glomerulus / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013859:Thiocarbamates / Q000494:pharmacology
D000873:Anthracenes; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D002104:Cadmium; C432165:pyrazolanthrone; C020972:pyrrolidine dithiocarbamic acid; D048031:JNK Mitogen-Activated Protein Kinases