Reactive oxygen species-mediated regulation of the Na+–H+ exchanger 1 gene expression connects intracellular redox status with cells' sensitivity to death triggers

Akram, Sufyan; Teong, Huey Fern; Fliegel, Larry; Pervaiz, Shazib; Clément, Marie‐Véronique

doi:10.1038/sj.cdd.4401775

Cited by 76 publications

(64 citation statements)

References 40 publications

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“…Conversely, antioxidant treatment is known to attenuate NHE activity [71]. Interestingly, ROS was previously shown to enhance NHE1 gene expression [72]. Thus, it is apparent from our data that ROS production and NHE1 activation upon stimulation with MG are dependent on each other.…”

Section: Discussionsupporting

confidence: 47%

Endothelial Na + /H + exchanger NHE1 participates in redox-sensitive leukocyte recruitment triggered by methylglyoxal

Qadri

Shao‐Horn

Cayabyab

et al. 2014

Cardiovasc Diabetol

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Background: Excessive levels of methylglyoxal (MG) encountered in diabetes foster enhanced leukocyte-endothelial cell interactions, mechanisms of which are incompletely understood. MG genomically upregulates endothelial serum-and glucocorticoid-inducible kinase 1 (SGK1) which orchestrates leukocyte recruitment by regulating the activation and expression of transcription factors and adhesion molecules. SGK1 regulates a myriad of ion channels and carriers including the Na

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Section: Discussionsupporting

confidence: 47%

Endothelial Na + /H + exchanger NHE1 participates in redox-sensitive leukocyte recruitment triggered by methylglyoxal

Qadri

Shao‐Horn

Cayabyab

et al. 2014

Cardiovasc Diabetol

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“…Chronic decrease in NHE1 levels could impair cell growth through accumulation in the G2/M phase of the cell cycle 9 or induce acidification of the intracellular milieu. 8 To that regard, exposure of L6 1.1 kb cells to nontoxic concentrations of H 2 O 2 induced cell growth arrest; however, the growth arrest was reversible along with the reactivation of NHE1 promoter upon incubation of the cells in medium containing 10% FBS following incubation with H 2 O 2 .…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, addition of exogenous H 2 O 2 inhibited NHE1 promoter activity and protein expression with a concomitant increase in cell sensitivity to death triggers. 8 In mammalian cells, the NHE family consists of nine isoforms, NHE1 to NHE-9. Apart from its role as a principal regulator of pHi and cell volume, the ubiquitously expressed subtype NHE1 has been implicated in cell proliferation and transformation (for a review, see Putney et al 9 ).…”

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confidence: 99%

Oxidative repression of NHE1 gene expression involves iron-mediated caspase activity

et al. 2007

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The mechanism of Na þ /H þ exchanger 1 (NHE1) gene repression upon exposure of cells to non-apoptotic concentrations of hydrogen peroxide (H 2 O 2 ) was investigated. We show that continuous presence of H 2 O 2 was not required for inhibition of NHE1 promoter activity. However, the downregulation of NHE1 promoter activity and protein expression was abrogated by the presence of beta mercaptoethanol (bME) and dithiothreitol. The pan-caspase inhibitor zVAD-fmk also blocked the effect of H 2 O 2 on NHE1 promoter activity and expression, but unlike bME, caspase inhibition was ineffective in rescuing the early phase of NHE1 repression. Interestingly, the effect of caspase inhibition was observed only after 9 h of exposure to H 2 O 2 and completely restored NHE1 promoter activity by 18-24 h. Using tetrapeptide inhibitors of a variety of caspases and siRNA-mediated gene silencing, caspases 3 and 6 were identified as mediators of H 2 O 2 -induced NHE1 repression, independent of initiator/amplifier caspase activation. Furthermore, incubation of cells with the iron chelator, desferioxamine, not only blocked the activities of caspases 3 and 6, but also affected NHE1 promoter and protein expression in a manner similar to zVAD-fmk. These data show that a mild oxidative stress represses NHE1 promoter activity and expression via an early oxidation phase blocked by reducing agents, and a late phase requiring an iron-dependent increase in caspases 3 and 6 activities.

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“…Moreover, increased free radicals mutilate the DNA in cancer cells and inactivates the genes that encode p53, ultimately leading to these cells resisting apoptosis (Halliwell, 2007;Vera-Ramirez et al, 2011). Continuous oxidative stress is a result of high levels of reactive oxygen species residue oxidation (Akram et al, 2006). Among oncogenes that are affected by ROS and activated in breast cancer cells, Raf-1 can be named that encoding the serine/ threonine kinase involved in cell proliferation signals.…”

Section: Oxidative Stress and Breast Cancermentioning

confidence: 99%

Roles of Oxidative Stress in the Development and Progression of Breast Cancer

Nourazarian¹,

Kangari²,

Salmaninejad³

2014

Asian Pacific Journal of Cancer Prevention

143

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Oxidative stress is caused by an imbalance in the redox status of the body. In such a state, increase of free radicals in the body can lead to tissue damage. One of the most important species of free radicals is reactive oxygen species (ROS) produced by various metabolic pathways, including aerobic metabolism in the mitochondrial respiratory chain. It plays a critical role in the initiation and progression of various types of cancers. ROS affects different signaling pathways, including growth factors and mitogenic pathways, and controls many cellular processes, including cell proliferation, and thus stimulates the uncontrolled growth of cells which encourages the development of tumors and begins the process of carcinogenesis. Increased oxidative stress caused by reactive species can reduce the body's antioxidant defense against angiogenesis and metastasis in cancer cells. These processes are main factors in the development of cancer. Bimolecular reactions cause free radicals in which create such compounds as malondialdehyde (MDA) and hydroxyguanosine. These substances can be used as indicators of cancer. In this review, free radicals as oxidizing agents, antioxidants as the immune system, and the role of oxidative stress in cancer, particularly breast cancer, have been investigated in the hope that better identification of the factors involved in the occurrence and spread of cancer will improve the identification of treatment goals.

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Reactive oxygen species-mediated regulation of the Na+–H+ exchanger 1 gene expression connects intracellular redox status with cells' sensitivity to death triggers

Cited by 76 publications

References 40 publications

Endothelial Na + /H + exchanger NHE1 participates in redox-sensitive leukocyte recruitment triggered by methylglyoxal

Endothelial Na + /H + exchanger NHE1 participates in redox-sensitive leukocyte recruitment triggered by methylglyoxal

Oxidative repression of NHE1 gene expression involves iron-mediated caspase activity

Roles of Oxidative Stress in the Development and Progression of Breast Cancer

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