2,4-Dinitrophenol induces apoptosis in As4.1 juxtaglomerular cells through rapid depletion of GSH.
2,4-Dinitrophenol (DNP) is an uncoupler of oxidative phosphorylation in mitochondria. Here, we investigated the in vitro effect of DNP on apoptosis and the involvement of reactive oxygen species (ROS) in As4.1 juxtaglomerular cell death. Dose- and time-dependent induction of apoptosis was evidenced by flow cytometric detection of sub-G1 DNA content and annexin V binding assay. The intracellular H(2)O(2) and O(2)(-) levels were markedly increased in DNP-treated cells. However, the reduction of intracellular H(2)O(2) level by Tiron and catalase did not prevent apoptosis induced by DNP. Moreover, DNP rapidly reduced intracellular GSH content in As4.1 cells. Taken together, apoptosis in DNP-treated As4.1 cells is correlated with the rapid change of intracellular GSH levels rather than ROS levels.
Han
Yong Hwan
YH
Department of Physiology, Medical School, Institute for Medical Sciences, Center for Healthcare Technology Development, Chonbuk National University, Jeonju 561-180, Republic of Korea.
Kim
Sung Zoo
SZ
Kim
Suhn Hee
SH
Park
Woo Hyun
WH
D019297:2,4-Dinitrophenol / Q000633:toxicity*; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D004247:DNA / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D007606:Juxtaglomerular Apparatus / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014475:Uncoupling Agents / Q000633:toxicity; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D017304:Annexin A5; D017382:Reactive Oxygen Species; D014475:Uncoupling Agents; D004247:DNA; D005978:Glutathione; D019297:2,4-Dinitrophenol