Thioredoxin overexpression in HT‐1080 cells induced cellular senescence and sensitization to gamma radiation

Byun, Hee Sun; Cho, Eun Wie; Kim, Jin Sik; Moon, Myung Sook; Yum, Jung Joo; Kim, Kug Chan; Kim, In Gyu

doi:10.1016/j.febslet.2005.06.023

Cited by 19 publications

(17 citation statements)

References 28 publications

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“…Byun et al have shown that increased TXN1 expression is associated with elevated radiation sensitivity through increased apoptosis and senescence [39]. We propose similar consequences for the radiation-induced up-regulation of TXN1 in miR-525-3p blocked cells.…”

Section: Discussionsupporting

confidence: 54%

“…Four of the directly regulated proteins (ARRB1, TXN1, HSPA9 and hnRNP K) have possible involvement in the radiation response [39-44]. Immunoblotting confirmed the results of the original proteomic screening by showing radiation-induced up-regulation of ARRB1, TXN1, HSPA9 and hnRNP K 12 h after 2.5 Gy exposures in the presence of anti-miR-525-3p (Figure 5).…”

Section: Resultsmentioning

confidence: 57%

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Cell Survival Following Radiation Exposure Requires miR-525-3p Mediated Suppression of ARRB1 and TXN1

et al. 2013

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BackgroundmicroRNAs (miRNAs) are non-coding RNAs that alter the stability and translation efficiency of messenger RNAs. Ionizing radiation (IR) induces rapid and selective changes in miRNA expression. Depletion of the miRNA processing enzymes Dicer or Ago2 reduces the capacity of cells to survive radiation exposure. Elucidation of critical radiation-regulated miRNAs and their target proteins offers a promising approach to identify new targets to increase the therapeutic effectiveness of the radiation treatment of cancer.Principal FindingsExpression of miR-525-3p is rapidly up-regulated in response to radiation. Manipulation of miR-525-3p expression in irradiated cells confirmed that this miRNA mediates the radiosensitivity of a variety of non-transformed (RPE, HUVEC) and tumor-derived cell lines (HeLa, U2-Os, EA.hy926) cell lines. Thus, anti-miR-525-3p mediated inhibition of the increase in miR-525-3p elevated radiosensitivity, while overexpression of precursor miR-525-3p conferred radioresistance. Using a proteomic approach we identified 21 radiation-regulated proteins, of which 14 were found to be candidate targets for miR-525-3p-mediated repression. Luciferase reporter assays confirmed that nine of these were indeed direct targets of miR-525-3p repression. Individual analysis of these direct targets by RNAi-mediated knockdown established that ARRB1, TXN1 and HSPA9 are essential miR-525-3p-dependent regulators of radiation sensitivity.ConclusionThe transient up-regulation of miR-525-3p, and the resultant repression of its direct targets ARRB1, TXN1 and HSPA9, is required for cell survival following irradiation. The conserved function of miR-525-3p across several cell types makes this microRNA pathway a promising target for modifying the efficacy of radiotherapy.

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Section: Discussionsupporting

confidence: 54%

Section: Resultsmentioning

confidence: 57%

Cell Survival Following Radiation Exposure Requires miR-525-3p Mediated Suppression of ARRB1 and TXN1

et al. 2013

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“…Hwang et al reported that thioredoxin might regulate the cell cycle and growth through a novel modulation of the Jab1-mediated proliferation signals (Hwang et al, 2004). Byun et al also reported that thioredoxin overexpression increased the expression of cyclin D1, a component of the core cell cycle machinery (Byun et al, 2005). The result of Byun et al is in accord with the results of this study that thioredoxin regulates the expression of cyclin D1.…”

Section: Discussionsupporting

confidence: 90%

Polyamine depletion partially reduces the radiation-induced cell death via cell cycle delay mediated by thioredoxin

Moon

Kim

et al. 2006

Cell Biol Toxicol

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In previous studies, polyamine depletion by DFMO (alpha-difluoromethylornithine)-treatment reduced H(2)O(2)-induced apoptotic cell death by reduction of ferric ion uptake. In the present study, we analyzed the reduction of radiation-induced cell death by polyamine depletion. Exposure of HT29 cells to radiation induced severe cell death, but when cells were pretreated with DFMO, a specific inhibitor of polyamine biosynthesis, radiation-induced cell death was reduced to 50-60% of control. Cell cycle analysis showed that, in these cells, the time to reach the G(2)/M phase arrest was delayed for 20-24 h compared to the control cells, at which stage the fate of cells exposed to ionizing radiation is determined. DFMO-treated cells also showed a low level of thioredoxin, which is a high-level determinant of the cellular fate. To investigate the relationship between the G(2)/M phase arrest and the reduction of thioredoxin caused by polyamine depletion, we also analyzed thioredoxin-antisensed (asTRX) HT29 cells as for DFMO-treated cells. In asTRX-transfected cells, the gamma-irradiation-induced G(2)/M phase arrest was also significantly delayed and radiation-induced cell death was profoundly reduced, as in the DFMO-treated cells. Both sets of cells showed a decrease of cyclin D1 and an increment of HSP25, which are involved in radiation-induced cell cycle progress. Overall, these results suggest that polyamines are essential for normal cell death of HT29 cells triggered by gamma-radiation and that this is partially mediated by the regulation of thioredoxin expression.

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“…In this experimental model, Trx overexpression inhibits the ASK1/JNK pathway [70, 71]. The overexpression or administration of human recombinant Trx (rTrx) on PC12 cells attenuates MPP + neurotoxicity [72, 73]. Overexpression of human Trx1 and Trx2 protects retinal ganglion cells against oxidative stress-induced neurodegeneration [74].…”

Section: Ts and Neuroprotectionmentioning

confidence: 99%

Thioredoxin System Regulation in the Central Nervous System: Experimental Models and Clinical Evidence

Silva-Adaya

Gonsebatt

Guevara

2014

Oxidative Medicine and Cellular Longevity

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The reactive oxygen species produced continuously during oxidative metabolism are generated at very high rates in the brain. Therefore, defending against oxidative stress is an essential task within the brain. An important cellular system against oxidative stress is the thioredoxin system (TS). TS is composed of thioredoxin, thioredoxin reductase, and NADPH. This review focuses on the evidence gathered in recent investigations into the central nervous system, specifically the different brain regions in which the TS is expressed. Furthermore, we address the conditions that modulate the thioredoxin system in both, animal models and the postmortem brains of human patients associated with the most common neurodegenerative disorders, in which the thioredoxin system could play an important part.

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Thioredoxin overexpression in HT‐1080 cells induced cellular senescence and sensitization to gamma radiation

Cited by 19 publications

References 28 publications

Cell Survival Following Radiation Exposure Requires miR-525-3p Mediated Suppression of ARRB1 and TXN1

Cell Survival Following Radiation Exposure Requires miR-525-3p Mediated Suppression of ARRB1 and TXN1

Polyamine depletion partially reduces the radiation-induced cell death via cell cycle delay mediated by thioredoxin

Thioredoxin System Regulation in the Central Nervous System: Experimental Models and Clinical Evidence

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