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

• Published in: Molecular immunology Vol. 43; no. 7; pp. 915 - 926
• Main Authors: Yao, Genhong, Yang, Lingsong, Hu, Yali, Liang, Jun, Liang, Junfeng, Hou, Yayi
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2006
• Subjects: Animals; Annexin A5 - analysis; Apoptosis; Caspase 3; Caspase 8; Caspase Inhibitors; Caspases - metabolism; DNA Fragmentation; Fluorescein-5-isothiocyanate - analysis; Membrane Potentials - drug effects; Mice; Mitochondria - drug effects; Mitochondrial depolarization; Nonylphenol; Phenols - pharmacology; Protease Inhibitors - pharmacology; T-Lymphocytes - drug effects; T-Lymphocytes - enzymology; Thymocytes; Thymus Gland - cytology; Thymus Gland - immunology; Nonylphenol; Thymocytes; Mitochondrial depolarization; Caspase-3; Apoptosis
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2005.06.031

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.