Nonylphenol-induced thymocyte apoptosis involved caspase-3 activation and mitochondrial depolarization

• DOI: 10.1016/j.molimm.2005.06.031
• Publication Date: 2005-07-26T15:00:16Z
• Authors: Genhong Yao; Lingsong Yang; Yali Hu; Jun Liang; Junfeng Liang; Yayi Hou
• Keywords: Caspase 8; 0303 health sciences; Caspase 3; T-Lymphocytes; Apoptosis; DNA Fragmentation; Thymus Gland; Caspase Inhibitors; Membrane Potentials; Mitochondria; Mice; 03 medical and health sciences; Phenols; Caspases; Animals; Protease Inhibitors; Annexin A5; Fluorescein-5-isothiocyanate

Although the effect of 4-nonylphenol on cells of immune system have long been recognized, little is known about the effect of 4-nonylphenol on the induction of apoptosis and related signaling events in the lymphoid cells. In the present study, we used cultured thymocytes of mice to investigate the ability of 4-nonylphenol to induce the apoptosis of thymocytes and to explore the role of signal transduction pathway leading to apoptosis. The results showed that the cytotoxic effects of 4-nonyphenol involved DNA fragmentation (DNA ladder), characteristic of apoptosis. Staining of 4-nonyphenol-treated thymocytes with DNA-binding fluorochrome Hoechst 33258 showed the typical apoptotic nuclei condensation and fragmentation of chromatin. The rates of apoptosis of the 4-nonylphenol-treated thymocytes increased significantly at 4 and 6 h, which were determined by analysis of hypodiploid cells and FITC-Annexin V and PI double staining. Flow cytometer analysis also revealed that the loss of mitochondrial membrane potential and increased activity of caspase-3 occurred concomitantly with the onset of 4-nonyphenol-induced apoptosis. Furthermore, a caspase-3 inhibitor, z-DEVD-fmk protected thymocytes from apoptosis induced by 4-nonyphenol. These results suggest that 4-nonylphenol induces thymocyte apoptosis via caspase-3 activation and mitochondrial depolarization.