title: The role of protein kinase C alpha translocation in radiation-induced bystander effect.
abstract: Ionizing radiation is a well known human carcinogen. Evidence accumulated over the past decade suggested that extranuclear/extracellular targets and events may also play a critical role in modulating biological responses to ionizing radiation. However, the underlying mechanism(s) of radiation-induced bystander effect is still unclear. In the current study, AL cells were irradiated with alpha particles and responses of bystander cells were investigated. We found out that in bystander AL cells, protein kinase C alpha (PKCα) translocated from cytosol to membrane fraction. Pre-treatment of cells with PKC translocation inhibitor chelerythrine chloride suppressed the induced extracellular signal-regulated kinases (ERK) activity and the increased cyclooxygenase 2 (COX-2) expression as well as the mutagenic effect in bystander cells. Furthermore, tumor necrosis factor alpha (TNFα) was elevated in directly irradiated but not bystander cells; while TNFα receptor 1 (TNFR1) increased in the membrane fraction of bystander cells. Further analysis revealed that PKC activation caused accelerated internalization and recycling of TNFR1. Our data suggested that PKCα translocation may occur as an early event in radiation-induced bystander responses and mediate TNFα-induced signaling pathways that lead to the activation of ERK and up-regulation of COX-2.
authors.affiliation: College of Life Sciences, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Zihui
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Hefei Institute of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China.
authors.forename: An
authors.initials: A
authors.lastname: Xu
authors.affiliation: Hefei Institute of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Wu
authors.affiliation: Center for Radiological Research, College of Physicians &Surgeons, Columbia University, New York, NY10032, USA.
authors.forename: Tom K
authors.initials: TK
authors.lastname: Hei
authors.affiliation: College of Life Sciences, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Hong
mesh_terms: D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D024201:Bystander Effect / Q000187:drug effects / Q000528:radiation effects*; D018957:CD59 Antigens / Q000378:metabolism; D016466:CHO Cells; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006224:Cricetinae; D003412:Cricetulus; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D004790:Enzyme Induction / Q000187:drug effects / Q000528:radiation effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D011839:Radiation, Ionizing; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053119:Benzophenanthridines; D018957:CD59 Antigens; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; C016299:chelerythrine; D051546:Cyclooxygenase 2; D051571:Protein Kinase C-alpha; D048049:Extracellular Signal-Regulated MAP Kinases