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The role of protein kinase C alpha translocation in radiation-induced bystander effect.

Fang Z, Xu A, Wu L, Hei TK, Hong M - Sci Rep (2016)

Bottom Line: However, the underlying mechanism(s) of radiation-induced bystander effect is still unclear.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.

View Article: PubMed Central - PubMed

Affiliation: College of Life Sciences, South China Agricultural University, Guangzhou, 510642, China.

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.

No MeSH data available.


Related in: MedlinePlus

Proposed scheme of PKC-mediated pathway in bystander responses.
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f4: Proposed scheme of PKC-mediated pathway in bystander responses.

Mentions: Although bystander effect has been well documented over the past decade, its underlying mechanism is still poorly understood. Here we focused our study within an early time frame after irradiation, and found out that within 15 min, PKC translocated from cytosol to membrane fraction in bystander cells, possibly in response to the increased level of TNFα in the irradiated system. In turn, the translocation (and thus activation) of PKC accelerated the internalization and recycling of TNFR1, which resulted in increased amount of the TNFR1 present on the cell surface. These events thus enable bystander cells to perceive signals secreted by directly irradiated cells and subsequently lead to activation of ERK and elevated COX-2 expression (Fig. 4). Our current data suggested a critical role of PKC in bystander responses, especially at early time points after irradiation. The identification of PKC as a positive mediator for the TNFα induced signaling pathways helps us better understand the molecular and cellular mechanisms of radiation-induced bystander effect.


The role of protein kinase C alpha translocation in radiation-induced bystander effect.

Fang Z, Xu A, Wu L, Hei TK, Hong M - Sci Rep (2016)

Proposed scheme of PKC-mediated pathway in bystander responses.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4863171&req=5

f4: Proposed scheme of PKC-mediated pathway in bystander responses.
Mentions: Although bystander effect has been well documented over the past decade, its underlying mechanism is still poorly understood. Here we focused our study within an early time frame after irradiation, and found out that within 15 min, PKC translocated from cytosol to membrane fraction in bystander cells, possibly in response to the increased level of TNFα in the irradiated system. In turn, the translocation (and thus activation) of PKC accelerated the internalization and recycling of TNFR1, which resulted in increased amount of the TNFR1 present on the cell surface. These events thus enable bystander cells to perceive signals secreted by directly irradiated cells and subsequently lead to activation of ERK and elevated COX-2 expression (Fig. 4). Our current data suggested a critical role of PKC in bystander responses, especially at early time points after irradiation. The identification of PKC as a positive mediator for the TNFα induced signaling pathways helps us better understand the molecular and cellular mechanisms of radiation-induced bystander effect.

Bottom Line: However, the underlying mechanism(s) of radiation-induced bystander effect is still unclear.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.

View Article: PubMed Central - PubMed

Affiliation: College of Life Sciences, South China Agricultural University, Guangzhou, 510642, China.

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.

No MeSH data available.


Related in: MedlinePlus