Effects of pentachlorophenol and tetrachlorohydroquinone on mitogen-activated protein kinase pathways in Jurkat T cells.
When Jurkat human T cells were incubated with 20 microM of pentachlorophenol (PCP) or its metabolite, tetrachlorohydroquinone (TCHQ), for 10 hr, flow cytometric analyses revealed marked increase in the number of apoptotic cells. DNA fragmentation was also observed in these cells. TCHQ was more potent than PCP in causing apoptosis. After incubation with 20 microM TCHQ for 1 hr, all mitogen-activated protein kinases (MAPKs) examined [i.e., extracellular signal-regulated protein kinase (ERK), p38, and c-Jun NH(2)-terminal kinase (JNK)] were phosphorylated, whereas no clear phosphorylation was induced by PCP. TCHQ-induced apoptosis was markedly suppressed by treatment with a p38 inhibitor (SB203580) and mildly (but significantly) suppressed by treatment with a MAPK/ERK kinase inhibitor (U0126). When cells were treated with both inhibitors at the same time, TCHQ-induced apoptosis disappeared almost completely. PCP-induced apoptosis was also suppressed by SB203580 and/or U0126. Nevertheless, treatment with LL-Z1640-2, which inhibits JNK phosphorylation, did not suppress the apoptosis caused by either TCHQ or PCP. Thus, p38 and ERK appear to be important signal transduction pathways leading to apoptosis in a human T-cell line exposed to a ubiquitous pollutant or its metabolite in the general and occupational environment.
Wispriyono
Bambang
B
Department of Environmental Toxicology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanashi-ku, Kitakyushu 807-8555, Japan.
Matsuoka
Masato
M
Igisu
Hideki
H
D017209:Apoptosis; D018929:Cell Culture Techniques; D004249:DNA Damage; D004785:Environmental Pollutants / Q000009:adverse effects*; D005434:Flow Cytometry; D006801:Humans; D006873:Hydroquinones / Q000009:adverse effects*; D019169:Jurkat Cells; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D010416:Pentachlorophenol / Q000009:adverse effects*; D015398:Signal Transduction
D004785:Environmental Pollutants; D006873:Hydroquinones; D010416:Pentachlorophenol; D020928:Mitogen-Activated Protein Kinases