UVB Radiation Induces Persistent Activation of Ribosome and Oxidative Phosphorylation Pathways

Tsai, Min-Lung; Chang, Kun-Yu; Chiang, Chi-Shiun; Shu, Wun‐Yi; Weng, Tsai-Chun; Chen, Chaang Ray; Huang, Ching-Lung; Lin, Hua‐Kuo; Hsu, Ian C.

doi:10.1667/rr1625.1

Cited by 17 publications

(21 citation statements)

References 44 publications

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“…Table S1 shows the number of DEGs and SGs in each exposed group, and no SG was observed between the internal control samples. The SGs of the positive control revealed genes involved in oxidative phosphorylation and ribosome pathways, which are in good agreement with prior studies in which other human cell types were used as experimental models [22], [29]–[32]. The results of the internal and positive controls indicated that the loop-designed microarray approach is a reliable system for screening the transcriptional profiles of HaCaT cells exposed to ELF-EMFs.…”

Section: Resultssupporting

confidence: 88%

Extremely Low-Frequency Electromagnetic Fields Cause G1 Phase Arrest through the Activation of the ATM-Chk2-p21 Pathway

et al. 2014

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In daily life, humans are exposed to the extremely low-frequency electromagnetic fields (ELF-EMFs) generated by electric appliances, and public concern is increasing regarding the biological effects of such exposure. Numerous studies have yielded inconsistent results regarding the biological effects of ELF-EMF exposure. Here we show that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT cells, inhibiting cell proliferation. To present well-founded results, we comprehensively evaluated the biological effects of ELF-EMFs at the transcriptional, protein, and cellular levels. Human HaCaT cells from an immortalized epidermal keratinocyte cell line were exposed to a 1.5 mT, 60 Hz ELF-EMF for 144 h. The ELF-EMF could cause G1 arrest and decrease colony formation. Protein expression experiments revealed that ELF-EMFs induced the activation of the ATM/Chk2 signaling cascades. In addition, the p21 protein, a regulator of cell cycle progression at G1 and G2/M, exhibited a higher level of expression in exposed HaCaT cells compared with the expression of sham-exposed cells. The ELF-EMF-induced G1 arrest was diminished when the CHK2 gene expression (which encodes checkpoint kinase 2; Chk2) was suppressed by specific small interfering RNA (siRNA). These findings indicate that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT cells, resulting in cell cycle arrest at the G1 phase. Based on the precise control of the ELF-EMF exposure and rigorous sham-exposure experiments, all transcriptional, protein, and cellular level experiments consistently supported the conclusion. This is the first study to confirm that a specific pathway is triggered by ELF-EMF exposure.

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Section: Resultssupporting

confidence: 88%

Extremely Low-Frequency Electromagnetic Fields Cause G1 Phase Arrest through the Activation of the ATM-Chk2-p21 Pathway

et al. 2014

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“…As discussed in our previous study, after UVB irradiation, the up-regulation of genes related to translation and ribosomal proteins in human fibroblasts suggested the need to renew UVB-damaged ribosomal proteins [18]. This corresponds to the result by the Casati and Walbot study, which showed that UVB irradiation induced direct ribosomal damage by crosslinking ribosomal proteins to RNA [41].…”

Section: Discussionsupporting

confidence: 80%

“…These 13 genes are related to chromosome condensation, DNA repair, cell cycle arrest, and apoptosis (Figure 3; related literatures are listed in Text S1). Previously we have validated our microarray system by RT-PCR with randomly selected genes, and the results were generally good (with R 2 ranged from 0.86 to 0.94) [18], [25]–[26]. To verify the significant gene expression patterns in this study, we further performed RT-PCR analysis for certain UVB-regulated genes, including the transcriptional targets of p53 ( GADD45A and CDKN1A ), one antioxidant gene ( GPX1 ), and three of the most discrepant genes ( MEN1 , NCAPH , and IL8 ).…”

Section: Resultsmentioning

confidence: 83%

“…We reanalyzed the microarray data of our previous study for comparison, which examined gene expressions of MRC-5 with the same dose of UVB irradiation and an identical microarray design [18]. The microarray experiments for both cell types were carried out by the same platform and with the same loop-design and data-processing procedures to minimize possible experimental and data-processing bias.…”

Section: Resultsmentioning

confidence: 99%

“…Under oncogenic stress, p53 directs cells to utilize mitochondrial oxidative phosphorylation rather than aerobic glycolysis that favors oncogenic process [16]–[17]. We previously showed that UVB irradiation induces the transactivation of genes functioning in oxidative phosphorylation in an untransformed human lung fibroblast [18]; other studies have also shown oxidative phosphorylation to be a major radiation-responsive pathway [19]–[21]. Because the large T antigen impedes p53 in SV40-transformed cells, and p53 regulates oxidative phosphorylation, this tumor-suppressive response might be considered inactive in SV40-transformed cells.…”

Section: Introductionmentioning

confidence: 99%

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Comparative Transcriptome Profiling of an SV40-Transformed Human Fibroblast (MRC5CVI) and Its Untransformed Counterpart (MRC-5) in Response to UVB Irradiation

et al. 2013

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Simian virus 40 (SV40) transforms cells through the suppression of tumor-suppressive responses by large T and small t antigens; studies on the effects of these two oncoproteins have greatly improved our knowledge of tumorigenesis. Large T antigen promotes cellular transformation by binding and inactivating p53 and pRb tumor suppressor proteins. Previous studies have shown that not all of the tumor-suppressive responses were inactivated in SV40-transformed cells; however, the underlying cause is not fully studied. In this study, we investigated the UVB-responsive transcriptome of an SV40-transformed fibroblast (MRC5CVI) and that of its untransformed counterpart (MRC-5). We found that, in response to UVB irradiation, MRC-5 and MRC5CVI commonly up-regulated the expression of oxidative phosphorylation genes. MRC-5 up-regulated the expressions of chromosome condensation, DNA repair, cell cycle arrest, and apoptotic genes, but MRC5CVI did not. Further cell death assays indicated that MRC5CVI was more sensitive than MRC-5 to UVB-induced cell death with increased caspase-3 activation; combining with the transcriptomic results suggested that MRC5CVI may undergo UVB-induced cell death through mechanisms other than transcriptional regulation. Our study provides a further understanding of the effects of SV40 transformation on cellular stress responses, and emphasizes the value of SV40-transformed cells in the researches of sensitizing neoplastic cells to radiations.

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Proteomic and network analysis of proteins regulated by REX1 in human embryonic stem cells

et al. 2015

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Recent studies have suggested that REX1 (reduced expression 1) plays an important role in pluripotency, proliferation, and differentiation. However, the molecular mechanisms involved in REX1-dependent regulation of diverse cellular processes remain unclear. To elucidate the regulatory functions of REX1 in human embryonic stem cells (hESCs), comparative proteomic analysis was performed on REX1 RNAi specifically silenced hESCs. Analysis of the proteome via nano-LC-MS/MS identified 140 differentially expressed proteins (DEPs) displaying a >2-fold difference in expression level between control and REX1 knockdown (KD) hESCs, which were then compared with transcriptome data and validated by quantitative real-time RT-PCR and Western blotting. These DEPs were analyzed by GO, pathway, and functional clustering analyses to determine the molecular functions of the proteins and pathways regulated by REX1. The REX1 KD-mediated DEPs mapped to major biological processes involved in the regulation of ribosome-mediated translation and mitochondrial function. Functional network analysis revealed a highly interconnected network among these DEPs and indicated that these interconnected proteins are predominantly involved in translation and the regulation of mitochondrial organization. These findings regarding REX1-mediated regulatory network have revealed the contributions of REX1 to maintaining the status of hESCs and have improved our understanding of the molecular events that underlie the fundamental properties of hESCs.

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UVB Radiation Induces Persistent Activation of Ribosome and Oxidative Phosphorylation Pathways

Cited by 17 publications

References 44 publications

Extremely Low-Frequency Electromagnetic Fields Cause G1 Phase Arrest through the Activation of the ATM-Chk2-p21 Pathway

Extremely Low-Frequency Electromagnetic Fields Cause G1 Phase Arrest through the Activation of the ATM-Chk2-p21 Pathway

Comparative Transcriptome Profiling of an SV40-Transformed Human Fibroblast (MRC5CVI) and Its Untransformed Counterpart (MRC-5) in Response to UVB Irradiation

Proteomic and network analysis of proteins regulated by REX1 in human embryonic stem cells

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