Advanced glycation end products induce T cell apoptosis: Involvement of oxidative stress, caspase and the mitochondrial pathway.
Accumulation of advanced glycation end products (AGEs) is a hallmark in aged people. T cells play important roles in maintaining homeostasis of immune function. This study investigated the effects of AGEs-bovine serum albumin (AGEs) in human T cells. Incubation of Jurkat and several immortalized T cell lines with AGEs resulted in cell death dose-dependently. AGEs-induced cell death was partially but significantly blocked by neutralizing antibodies recognizing receptor of AGEs. In addition to detecting DNA nick, simultaneous stainings of annexin V with 7-amino-actinomycin D further confirmed the apoptotic nature of cell death. AGEs also caused apoptosis in purified T cells. Although AGEs-induced apoptosis could be blocked by the pan-caspase inhibitor, Ala-Asp-fluomethyl ketone (Z-VAD-fmk), there was no activation of caspase-3, -5, -8 and -9. AGEs caused mitochondrial outer membrane permeabilization and this process was prevented by an antioxidant or Z-VAD-fmk. Furthermore, AGEs treatment led to translocation of apoptosis inducing factor (AIF) from the mitochondria into the nucleus. Altogether, this report demonstrated that AGEs induced T cell apoptosis in an oxidative stress-associated and caspase-dependent manner with involvement of the mitochondrial pathway. It is likely that AGEs-induced T cell apoptosis may play a role in T cell homeostasis in ageing.
Hung
Li-Feng
LF
Institute of Cellular and System Medicine, National Health Research Institute, Zhunan, Taiwan, Republic of China.
Huang
Kuo-Yen
KY
Yang
Deng-Ho
DH
Chang
Deh-Ming
DM
Lai
Jenn-Haung
JH
Ho
Ling-Jun
LJ
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002417:Cattle; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D019169:Jurkat Cells; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D021381:Protein Transport; D012710:Serum Albumin, Bovine / Q000378:metabolism* / Q000633:toxicity; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D000590:Amino Acid Chloromethyl Ketones; D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D017127:Glycation End Products, Advanced; C081628:advanced glycation end products-bovine serum albumin; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D012710:Serum Albumin, Bovine; D020169:Caspases