Ionizing irradiation induces apoptotic damage of salivary gland acinar cells via NADPH oxidase 1-dependent superoxide generation

Tateishi, Yohei; Sasabe, Eri; Ueta, Eisaku; Yamamoto, Tetsuya

doi:10.1016/j.bbrc.2007.11.039

Cited by 62 publications

(47 citation statements)

References 41 publications

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“…We have not investigated the mechanism of ROS production by ERK in the present study, but previous reports speculate that ERK phosphorylates integrin or focal adhesion proteins, such as Src/FAK or paxillin, to induce Rac1-associated NADPH oxidasedependent generation of ROS (47). Furthermore, plasma membrane-bound NADPH oxidase is primarily responsible for intracellular ROS generation in response to ionizing ␣ particles, x-ray, or ␥-radiation (48,49). Therefore, ERK may induce ROS under our experimental conditions, although the cell lines used in individual experiments are different.…”

Section: Discussionmentioning

confidence: 98%

Ionizing Radiation Induces Cellular Senescence of Articular Chondrocytes via Negative Regulation of SIRT1 by p38 Kinase

Hong

Lee

Kim

et al. 2010

Journal of Biological Chemistry

148

123

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Radiotherapy is increasingly used in the treatment of joint diseases, but limited information is available on the effects of radiation on cartilage. Here, we characterize the molecular mechanisms leading to cellular senescence in irradiated primary cultured articular chondrocytes. Ionizing radiation (IR) causes activation of ERK, in turn generating intracellular reactive oxygen species (ROS) with induction of senescence-associated ␤-galactosidase (SA-␤-gal) activity. ROS activate p38 kinase, which further promotes ROS generation, forming a positive feedback loop to sustain ROS-p38 kinase signaling. The ROS inhibitors, nordihydroguaiaretic acid and GSH, suppress phosphorylation of p38 and cell numbers positive for SA-␤-gal following irradiation. Moreover, inhibition of the ERK and p38 kinase pathways leads to blockage of IR-induced SA-␤-gal activity via reduction of ROS generation. Although JNK is activated by ROS, this pathway is not associated with cellular senescence of chondrocytes. Interestingly, IR triggers down-regulation of SIRT1 protein expression but not the transcript level, indicative of post-transcriptional cleavage of the protein. SIRT1 degradation is markedly blocked by SB203589 or MG132 after IR treatment, suggesting that cleavage occurs as a result of binding with p38 kinase, followed by processing via the 26 S proteasomal degradation pathway. Overexpression or activation of SIRT1 significantly reduces the IR-induced senescence phenotype, whereas inhibition of SIRT1 activity induces senescence. Based on these findings, we propose that IR induces cellular senescence of articular chondrocytes by negative post-translational regulation of SIRT1 via ROS-dependent p38 kinase activation.

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Section: Discussionmentioning

confidence: 98%

Ionizing Radiation Induces Cellular Senescence of Articular Chondrocytes via Negative Regulation of SIRT1 by p38 Kinase

Hong

Lee

Kim

et al. 2010

Journal of Biological Chemistry

148

123

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“…Exposure of different types of cells to ionizing radiation has been shown to induce intracellular superoxide and hydrogen peroxide generation as a result of Nox activation or up-regulation (Narayanan et al, 1997;Collins-Underwood et al, 2008;Tateishi et al, 2008). Radiation-induced ROS generation may trigger secondary cellular responses, such as expression of inflammatory molecules, activation of the redox-sensitive transcription factors (such as nuclear factor-B), activation of mitogen-activated protein kinases (MAPKs) [including ERK1/2 and p38] and the stress kinase JNK, and cell apoptosis (Azzam et al, 2002;Collins-Underwood et al, 2008;Tateishi et al, 2008).…”

Section: B Physical Challengesmentioning

confidence: 99%

“…Radiation-induced ROS generation may trigger secondary cellular responses, such as expression of inflammatory molecules, activation of the redox-sensitive transcription factors (such as nuclear factor-B), activation of mitogen-activated protein kinases (MAPKs) [including ERK1/2 and p38] and the stress kinase JNK, and cell apoptosis (Azzam et al, 2002;Collins-Underwood et al, 2008;Tateishi et al, 2008). In addition, people have found that acute exposure of keratinocytes to both UVA and UVB results in activation of Nox and generation of ROS (Wang and Kochevar, 2005;Van Laethem et al, 2006;Valencia and Kochevar, 2008).…”

Section: B Physical Challengesmentioning

confidence: 99%

NADPH Oxidase-Mediated Redox Signaling: Roles in Cellular Stress Response, Stress Tolerance, and Tissue Repair

2011

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“…It has been reported that intracellular ROS levels are quickly increased after exposure to IR and that elevated levels of ROS are sustained for several hours after initial IR exposure (32,179). NOX is responsible, in part, for a late increase in intracellular superoxide generation after exposure to IR (32,179).…”

Section: Ir and Radiation Therapymentioning

confidence: 99%

“…NOX is responsible, in part, for a late increase in intracellular superoxide generation after exposure to IR (32,179). IR-induced mitochondrial dysfunction, especially decreased electron transport chain complex I activity, produces a feed forward loop that contributes to persistent oxidative stress after irradiation (198).…”

Section: Ir and Radiation Therapymentioning

confidence: 99%

Redox-Mediated and Ionizing-Radiation-Induced Inflammatory Mediators in Prostate Cancer Development and Treatment

Liu

Holley

Zhao

et al. 2014

Antioxidants & Redox Signaling

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Significance: Radiation therapy is widely used for treatment of prostate cancer. Radiation can directly damage biologically important molecules; however, most effects of radiation-mediated cell killing are derived from the generated free radicals that alter cellular redox status. Multiple proinflammatory mediators can also influence redox status in irradiated cells and the surrounding microenvironment, thereby affecting prostate cancer progression and radiotherapy efficiency. Recent Advances: Ionizing radiation (IR)-generated oxidative stress can regulate and be regulated by the production of proinflammatory mediators. Depending on the type and stage of the prostate cancer cells, these proinflammatory mediators may lead to different biological consequences ranging from cell death to development of radioresistance. Critical Issues: Tumors are heterogeneous and dynamic communication occurs between stromal and prostate cancer cells, and complicated redox-regulated mechanisms exist in the tumor microenvironment. Thus, antioxidant and anti-inflammatory strategies should be carefully evaluated for each patient at different stages of the disease to maximize therapeutic benefits while minimizing unintended side effects. Future Directions: Compared with normal cells, tumor cells are usually under higher oxidative stress and secrete more proinflammatory mediators. Thus, redox status is often less adaptive in tumor cells than in their normal counterparts. This difference can be exploited in a search for new cancer therapeutics and treatment regimes that selectively activate cell death pathways in tumor cells with minimal unintended consequences in terms of chemo-and radio-resistance in tumor cells and toxicity in normal tissues. Antioxid. Redox Signal. 20, 1481-1500.

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Ionizing irradiation induces apoptotic damage of salivary gland acinar cells via NADPH oxidase 1-dependent superoxide generation

Cited by 62 publications

References 41 publications

Ionizing Radiation Induces Cellular Senescence of Articular Chondrocytes via Negative Regulation of SIRT1 by p38 Kinase

Ionizing Radiation Induces Cellular Senescence of Articular Chondrocytes via Negative Regulation of SIRT1 by p38 Kinase

NADPH Oxidase-Mediated Redox Signaling: Roles in Cellular Stress Response, Stress Tolerance, and Tissue Repair

Redox-Mediated and Ionizing-Radiation-Induced Inflammatory Mediators in Prostate Cancer Development and Treatment

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