title: Crosstalk between Fas and JNK determines lymphocyte apoptosis after ionizing radiation.
abstract: Radiation simultaneously activate Fas and JNK pathway in lymphocytes but their precise interaction is not clearly understood. Activation of Fas pathway is required for radiation induced apoptosis, however induction of JNK pathway may or may not contribute in apoptosis. Here we report that Fas, Fas associated death domain and total JNK are activated in a dose- and time-dependent radiation exposure. A biphasic pattern of phospho-JNK was found at lower doses (1 and 2 Gy), however at higher doses of radiation phospho-JNK was continuously activated. Interestingly, Fas ligand expression remained biphasic at all the doses of radiation. Our results suggest that the Fas pathway is the major player in radiation-induced apoptosis, with JNK playing a contributory role. We also observed that Fas ligand expression by radiation is dependent on JNK activation. We also propose that radiation activates JNK pathway, but sustained activation is required for maximal induction of apoptosis at later times. Our findings define a mechanism for crosstalk between JNK and Fas pathway in radiation-induced apoptosis, which may lead to the development of new therapeutic strategies.
authors.affiliation: Division of Radiation Biosciences, Institute of Nuclear Medicine & Allied Sciences, Defence Research Development Organization, Delhi, India.
authors.forename: Koganti
authors.initials: K
authors.lastname: Praveen
authors.forename: Nandita
authors.initials: N
authors.lastname: Saxena
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019169:Jurkat Cells; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000528:radiation effects*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D013997:Time Factors; D019014:fas Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D053200:Fas-Associated Death Domain Protein; D047428:Protein Kinase Inhibitors; D019014:fas Receptor; D048031:JNK Mitogen-Activated Protein Kinases