Hydrogen peroxide mediates arsenite activation of p70s6k and extracellular signal-regulated kinase

Jung, Dong Keun; Bae, Gyu‐Un; Kim, Yong Kee; Han, Seung-Hee; Choi, Wahn Soo; Kang, Hyeog; Seo, Dong Wan; Lee, Hoi Young; Cho, Eun Jung; Lee, Hyang-Woo; Han, Jeung‐Whan

doi:10.1016/s0014-4827(03)00320-3

Cited by 26 publications

(19 citation statements)

References 57 publications

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“…Our data imply that fluprostenol may also be included in this list. Furthermore, they substantiate earlier findings demonstrating that ROS is capable of activating p70 S6K (36,37).…”

Section: Discussionsupporting

confidence: 90%

PGF2α-associated vascular smooth muscle hypertrophy is ROS dependent and involves the activation of mTOR, p70S6k, and PTEN

Rice

Uddemarri

Desai

et al. 2008

Prostaglandins & Other Lipid Mediators

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Prostaglandin F 2α (PGF2α) increases reactive oxygen species (ROS) and induces vascular smooth muscle cell (VSMC) hypertrophy by largely unknown mechanism(s). To investigate the signaling events governing PGF2α -induced VSMC hypertrophy we examined the ability of the PGF2α analog, fluprostenol to elicit phosphorylation of Akt, the mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70 S6k ), glycogen synthase kinase-3β (GSK-3β), phosphatase and tensin homolog (PTEN), extracellular signal-regulated kinase 1/2 (ERK1/2) and Jun N-terminal kinase (JNK) in growth arrested A7r5 VSMC. Fluprostenol-induced hypertrophy was associated with increased ROS, mTOR translocation from the nucleus to the cytoplasm, along with Akt, mTOR, GSK-3β, PTEN and ERK1/2 but not JNK phosphorylation. Whereas inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 blocked fluprostenol-induced changes in total protein content, pretreatment with rapamycin or with the ERK1/2-MAPK inhibitor UO126 did not. Taken together, these findings suggest that fluprostenol-induced changes in A7R5 hypertrophy involve mTOR translocation and occur through PI3K-dependent mechanisms.

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“…Our data imply that fluprostenol may also be included in this list. Furthermore, they substantiate earlier findings demonstrating that ROS is capable of activating p70 S6K (36,37).…”

Section: Discussionsupporting

confidence: 90%

PGF2α-associated vascular smooth muscle hypertrophy is ROS dependent and involves the activation of mTOR, p70S6k, and PTEN

Rice

Uddemarri

Desai

et al. 2008

Prostaglandins & Other Lipid Mediators

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“…For example, depending on its concentration, H 2 O 2 can induce cell proliferation, mediate drug-induced apoptosis in many models (particularly in tumor cells), or at overwhelming levels bring about necrotic cell death. Indeed, there is a fair amount of controversy with respect to the relationship between PI3K signaling and H 2 O 2 production, with data supporting both an upstream and a downstream role of H 2 O 2 in PI3K signaling (62). However, in tumor cells, intracellular generation of H 2 O 2 , specifically in response to drug exposure, is independent of PI3K.…”

Section: Discussionmentioning

confidence: 99%

LY294002 and LY303511 Sensitize Tumor Cells to Drug-Induced Apoptosis via Intracellular Hydrogen Peroxide Production Independent of the Phosphoinositide 3-Kinase-Akt Pathway

Poh

Pervaiz²

2005

Cancer Research

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The phosphoinositide 3-kinase (PI3K)-Akt pathway is constitutively active in many tumors, and inhibitors of this prosurvival network, such as LY294002, have been shown to sensitize tumor cells to death stimuli. Here, we report a novel, PI3K-independent mechanism of LY-mediated sensitization of LNCaP prostate carcinoma cells to drug-induced apoptosis. Preincubation of tumor cells to LY294002 or its inactive analogue LY303511 resulted in a significant increase in intracellular hydrogen peroxide (H 2 O 2 ) production and enhanced sensitivity to nonapoptotic concentrations of the chemotherapeutic agent vincristine. The critical role of intracellular H 2 O 2 in LY-induced death sensitization is corroborated by transient transfection of cells with a vector containing human catalase gene. Indeed, overexpression of catalase significantly blocked the amplifying effect of LY pretreatment on caspase-2 and caspase-3 activation and cell death triggered by vincristine. Furthermore, the inability of wortmannin, another inhibitor of PI3K, to induce an increase in H 2 O 2 production at doses that effectively blocked Akt phosphorylation provides strong evidence to unlink inhibition of PI3K from intracellular H 2 O 2 production. These data strongly support death-sensitizing effect of LY compounds independent of the PI3K pathway and underscore the critical role of H 2 O 2 in creating a permissive intracellular milieu for efficient drug-induced execution of tumor cells. (Cancer Res 2005; 65(14): 6264-74)

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“…The response of TSC2 À/À MEFs to peroxide is somewhat puzzling, as basal ROS levels are significantly higher in TSC2 À/À cells, as a result of increased mitochondrial function (Finlay et al, 2005). Moreover, peroxide or arsenite treatment of JB6 cells (a mouse epidermal cell type) has been shown to lead to an increase in S6K and 4EBP1 activation (Bae et al, 1999;Huang et al, 2002;Jung et al, 2003). In addition, UV irradiation (which increases the amount of ROS in the cell) of HEK293 cells (Parrott and Templeton, 1999) and JB6 cells has been shown to increase the phosphorylation of S6K.…”

Section: Rosmentioning

confidence: 99%

Upstream of the mammalian target of rapamycin: do all roads pass through mTOR?

2006

Oncogene

348

309

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The mammalian target of rapamycin (mTOR) is a serine/ threonine kinase that controls many aspects of cellular physiology, including transcription, translation, cell size, cytoskeletal organization and autophagy. Recent advances in the mTOR signaling field have found that mTOR exists in two heteromeric complexes, mTORC1 and mTORC2. The activity of mTORC1 is regulated by the integration of many signals, including growth factors, insulin, nutrients, energy availability and cellular stressors such as hypoxia, osmotic stress, reactive oxygen species and viral infection. In this review we highlight recent advances in the mTOR signaling field that relate to how the two mTOR complexes are regulated, and we discuss stress conditions linked to the mTOR signaling network that have not been extensively covered in other reviews. Given the diversity of signals that have been shown to impinge on mTOR, we also speculate on other signaltransduction pathways that may be linked to mTOR in the future.

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Hydrogen peroxide mediates arsenite activation of p70s6k and extracellular signal-regulated kinase

Cited by 26 publications

References 57 publications

PGF2α-associated vascular smooth muscle hypertrophy is ROS dependent and involves the activation of mTOR, p70S6k, and PTEN

PGF2α-associated vascular smooth muscle hypertrophy is ROS dependent and involves the activation of mTOR, p70S6k, and PTEN

LY294002 and LY303511 Sensitize Tumor Cells to Drug-Induced Apoptosis via Intracellular Hydrogen Peroxide Production Independent of the Phosphoinositide 3-Kinase-Akt Pathway

Upstream of the mammalian target of rapamycin: do all roads pass through mTOR?

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