A critical role for Romo1-derived ROS in cell proliferation

Na, Ah Ram; Chung, Young-Min; Lee, Seung Baek; Park, Seon Ho; Lee, Myeong Sok; Yoo, Young

doi:10.1016/j.bbrc.2008.02.098

Cited by 82 publications

(96 citation statements)

References 21 publications

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“…The ROS level in these cells was downregulated by Romo1 knockdown itself (Figure 1), which is consistent with earlier reports. 28,29 This experiment was also carried out again in the cells treated with H 2 O 2 as a positive control. HeLa cells were transfected with 100 nM of control siRNA or Romo1 siRNA for 16 h and treated with H 2 O 2 (100 mM) for 1 h. As expected, ROS increase was observed in the cells transfected with control siRNA (Supplementary Figure S1b).…”

Section: Resultsmentioning

confidence: 99%

“…Romo1 knockdown was examined by western blotting (Figure 1g) or RT-PCR (Supplementary Figure S1f), and the result was consistent with earlier reports. [26][27][28][29] TNF-a-induced JNK activation and cell death are regulated by Romo1-mediated ROS production. We examined whether Romo1 regulated TNF-a-triggered JNK activation and cell death.…”

Section: Resultsmentioning

confidence: 99%

“…Consistent with this suggestion, we showed that Romo1 knockdown decreased ROS levels in both normal and tumor cells. 28,29 Taken together, Romo1 is an important modulator to supply ROS into the cytosol. Without any signal, Romo1 supplies the minimal level of ROS required for cell survival and proliferation through the basal binding of Romo1 to Bcl-X L .…”

Section: Discussionmentioning

confidence: 99%

“…[25][26][27] The ROS originating from the endogenous Romo1 protein appear to be indispensable for both normal and cancer cell proliferation, because Romo1 knockdown inhibits cell-cycle transition through inhibition of Erk activation and p27 Kip1 expression. 28,29 Romo1 expression is induced by an external stimulus such as 5-FU, and it is upregulated in senescent cells and in most cancer cells. 25,26,30 As the mitochondrial origin of ROS formation triggered by TNF-a is not clear, and Romo1 contributes to ROS production in the mitochondria, we investigated whether TNF-a-induced ROS are associated with Romo1.…”

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confidence: 99%

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TNF-α-induced ROS production triggering apoptosis is directly linked to Romo1 and Bcl-XL

et al. 2010

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Reactive oxygen species (ROS) produced by tumor necrosis factor-a (TNF-a) have an important function in cell death by activating c-Jun N-terminal kinase. However, the exact mechanism of mitochondrial ROS production, after TNF-a stimulation, is not clearly understood. In this study, we determined that ROS modulator 1 (Romo1) and B-cell lymphoma-extra large (Bcl-X L ) are directly associated with TNF-a-induced ROS production. In response to TNF-a, TNF complex II, which consists of receptorinteracting protein 1, TNF receptor-associated protein with death domain, TNF receptor-associated factor 2, Fas-associated death domain protein, and pro-caspase-8, binds to the C-terminus of Romo1 located in the mitochondria. Concurrently, Romo1 recruits Bcl-X L to reduce the mitochondrial membrane potential, resulting in ROS production and apoptotic cell death. On the basis of these results, we suggest that Romo1 is a molecular bridge between TNF-a signaling and the mitochondria for ROS production that triggers TNF-a-mediated apoptosis, as well as a novel target in the development of anti-inflammatory agents that block the origin of ROS production. Tumor necrosis factor-a (TNF-a) is a major mediator of inflammation. There are two main pathways in TNF-a signaling. One is the pro-survival/pro-inflammatory pathway that activates NF-kB and MAPK through TNF-a-induced signaling complex I. 1 After binding of the trimeric TNF-a to the cell surface receptor TNF-R1, the silencer of death domain dissociates from TNF-R1 complexes, and the TNF receptor-associated protein with death domain (TRADD) -an adaptor protein -binds to the cytoplasmic domain of the receptor. 2 TRADD recruits additional proteins including TNF receptor-associated factor 2 (TRAF2), receptor-interacting protein 1 (RIP1), and cellular inhibitor of apoptosis proteins to form TNF-a-induced signaling complex I. 3,4 The other TNF-a signaling pathway is the proapoptotic pathway through TNF-ainduced signaling complex II, in which reactive oxygen species (ROS), a caspase cascade, and the mitochondria function as downstream mediators. If TRADD, TRAF2, and RIP1 dissociate from the receptor, they recruit Fas-associated death domain protein (FADD) and pro-caspase-8 to form TNF-a-induced signaling complex II, which is implicated in signaling apoptosis. 5,6 This TNF-a-induced cell death pathway is normally blocked by concomitant activation of NF-kB.ROS generation, after TNF-a binding, has been reported to be involved in both cell survival and cell death, and the main source of ROS generation that contributes to TNF-a-induced cell death is the mitochondrion. 7-9 However, another study reported that NADPH oxidase is the source of ROS generation after TNF-a treatment. 10 ROS are known to contribute to cell death by inducing mitochondrial membrane permeabilization and sustaining c-Jun N-terminal kinase (JNK) activation. 11,12 JNK is activated by the activation of apoptosis signal-regulating kinase-1 or by ROS-mediated inactivation of MKPs. 13,14 There are several reports regarding the mech...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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TNF-α-induced ROS production triggering apoptosis is directly linked to Romo1 and Bcl-XL

et al. 2010

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“…These proteins were present in a wide range of organisms from fungi to mammals. It has been reported that Romo1 induces reactive oxygen species production in mitochondria, which may play an important role in redox signaling in cancer cells (44,45). A multiple alignment of these proteins is shown in Fig.…”

Section: Selk and Sels Define A New Eukaryotic Protein Family-mentioning

confidence: 99%

Selenoprotein K Binds Multiprotein Complexes and Is Involved in the Regulation of Endoplasmic Reticulum Homeostasis

Shchedrina

Everley

Zhang

et al. 2011

Journal of Biological Chemistry

117

129

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Inhibition of cellular proliferation and enhancement of hydrogen peroxide production in fibrosarcoma cell line by weak radio frequency magnetic fields

Castello

Hill

Sivo

et al. 2014

Bioelectromagnetics

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This study presents experimental data for the effects of weak radio frequency (RF) magnetic fields on hydrogen peroxide (H2O2) production and cellular growth rates of fibrosarcoma HT1080 cells in vitro. Cells were exposed either to 45 µT static magnetic fields (SMFs)-oriented vertical to the plane of growth or to SMFs combined with weak 5 and 10 MHz RF magnetic fields of 10 µTRMS intensity perpendicular to the static field. Cell numbers were reduced up to 30% on Day 2 for the cells exposed to the combination of SMF and a 10 MHz RF magnetic field compared with the SMF control cells. In addition, cells exposed to 10 MHz RF magnetic fields for 8 h increased H2O2 production by 55%. The results demonstrate an overall magnetic field-induced biological effect that shows elevated H2O2 levels with accompanying decrease in cellular growth rates.

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A critical role for Romo1-derived ROS in cell proliferation

Cited by 82 publications

References 21 publications

TNF-α-induced ROS production triggering apoptosis is directly linked to Romo1 and Bcl-XL

TNF-α-induced ROS production triggering apoptosis is directly linked to Romo1 and Bcl-XL

Selenoprotein K Binds Multiprotein Complexes and Is Involved in the Regulation of Endoplasmic Reticulum Homeostasis

Inhibition of cellular proliferation and enhancement of hydrogen peroxide production in fibrosarcoma cell line by weak radio frequency magnetic fields

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