The involvement of calcium and MAP kinase signaling pathways in the production of radiation-induced bystander effects.

نویسندگان

  • F M Lyng
  • P Maguire
  • B McClean
  • C Seymour
  • C Mothersill
چکیده

Much evidence now exists regarding radiation-induced bystander effects, but the mechanisms involved in the transduction of the signal are still unclear. The mitogen-activated protein kinase (MAPK) pathways have been linked to growth factor-mediated regulation of cellular events such as proliferation, senescence, differentiation and apoptosis. Activation of multiple MAPK pathways such as the ERK, JNK and p38 pathways have been shown to occur after exposure of cells to radiation and a variety of other toxic stresses. Previous studies have shown oxidative stress and calcium signaling to be important in radiation-induced bystander effects. The aim of the present study was to investigate MAPK signaling pathways in bystander cells exposed to irradiated cell conditioned medium (ICCM) and the role of oxidative metabolism and calcium signaling in the induction of bystander responses. Human keratinocytes (HPV-G cell line) were irradiated (0.005-5 Gy) using a cobalt-60 teletherapy unit. The medium was harvested 1 h postirradiation and transferred to recipient HPV-G cells. Phosphorylated forms of p38, JNK and ERK were studied by immunofluorescence 30 min-24 h after exposure to ICCM. Inhibitors of the ERK pathway (PD98059 and U0126), the JNK pathway (SP600125), and the p38 pathway (SB203580) were used to investigate whether bystander-induced cell death could be blocked. Cells were also incubated with ICCM in the presence of superoxide dismutase, catalase, EGTA, verapamil, nifedipine and thapsigargin to investigate whether bystander effects could be inhibited because of the known effects on calcium homeostasis. Activated forms of JNK and ERK proteins were observed after exposure to ICCM. Inhibition of the ERK pathway appeared to increase bystander-induced apoptosis, while inhibition of the JNK pathway appeared to decrease apoptosis. In addition, reactive oxygen species, such as superoxide and hydrogen peroxide, and calcium signaling were found to be important modulators of bystander responses. Further investigations of these signaling pathways may aid in the identification of novel therapeutic targets.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Radio-adaptive response of peripheral blood lymphocytes following bystander effects induced by preirradiated CHO-K1 cells using the micronucleus assay

Background: Radio-adaptive response and bystander effects are known phenomena occurring in cells following exposure to ionizing radiation (IR). In this study we examined possible radio-adaptation of lymphocytes following bystander effects induced by CHO-K1 cells. Materials and Methods: Whole blood and CHO-K1 cells were cultured in RPMI-1640 complete medium. Cells were separately irradiated with...

متن کامل

Radiation Bystander Effects Mechanism

  Introduction: Radiation Induced Bystander Effect (RIBE) which cause radiation effects in non-irradiated cells, has challenged the principle according to which radiation traversal through the nucleus of a cell is necessary for producing biological responses. What is the mechanism of this phenomenon? To have a better understanding of this rather ambiguous concept substantial number of original ...

متن کامل

Gene transcriptomic profile in arabidopsis thaliana mediated by radiation-induced bystander effects

Background: The in vivo radiation-induced bystander effects (RIBE) at the developmental, genetic, and epigenetic levels have been well demonstrated using model plant Arabidopsis thaliana (A. thaliana). However, the mechanisms underlying RIBE in plants are not clear, especially lacking a comprehensive knowledge about the genes and biological pathways involved in the RIBE in plants. Materials and...

متن کامل

Involvement of TRPM7 calcium channels and PI3K/AKT kinase pathway in protective effect of vascular endothelial growth factor in amyloid beta-induced model of Alzheimer’s disease

Background and Objective: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, in which cortical and hippocampus neurons death is the main target of neurodegeneration. In addition to extracellular beta amyloid accumulation and the production of neural tangles, one of effective factors in the pathology of Alzheimer's disease is vascular injury in the elderly including disturbanc...

متن کامل

Radiation-induced bystander effect following hypo- fraction technique of grid therapy by use of sensitive molecular markers

Introduction: Radiation-induced bystander effect (RIBE) is a well-known response associated with the induction of radiation effects in non-irradiated cells via signaling of hit ones. As this so-called phenomenon has been largely investigated in low dose levels, few studies focused on higher dose levels such as grid therapy. Grid therapy or spatially fractionated gri...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Radiation research

دوره 165 4  شماره 

صفحات  -

تاریخ انتشار 2006