Nuclear glutathione S-transferase π prevents apoptosis by reducing the oxidative stress-induced formation of exocyclic dna products

Kamada, Kensaku; Goto, Shinji; Okunaga, Tomohiro; Ihara, Yoshito; Tsuji, Kentaro; Kawai, Yoshichika; Uchida, Koji; Osawa, Toshihiko; Matsuo, Takayuki; Nagata, Izumi; Kondo, Takahito

doi:10.1016/j.freeradbiomed.2004.09.002

Cited by 50 publications

(44 citation statements)

References 39 publications

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“…Inhibition of nuclear localization of GSTp-sensitized cells to cytotoxicity suggested that nuclear GSTp protected DNA against anticancer drug-induced damage (52,53). Additional evidence supports the protective role of nuclear GSTp against H 2 O 2 -induced DNA damage (85). A negative relation between animal-type melanoma and nuclear GSTp levels also supports a critical role of nuclear GSTp in nuclear protection (138).…”

Section: Distribution Of Redox Systems In Nucleimentioning

confidence: 79%

“…The presence of the class theta GST T1-1 in the nucleus of mouse and human liver cells was confirmed with histochemical analysis (172). Nuclear expression of GSTpi (GSTp) occurs in cancer tissues (52,85,138), although it also was found in mitochondria (52). Increases in the expression of GSTp have been detected in precancerous cells and various cancer tissues, animal-type melanoma (138), hepatocarcinogenesis (165), prostate cancer (116), gynecologic cancers, urinary cancer cells (173), and glioma cells (2).…”

Section: Distribution Of Redox Systems In Nucleimentioning

confidence: 83%

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Redox Control Systems in the Nucleus: Mechanisms and Functions

Jones

2010

Antioxidants & Redox Signaling

176

125

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Proteins with oxidizable thiols are essential to many functions of cell nuclei, including transcription, chromatin stability, nuclear protein import and export, and DNA replication and repair. Control of the nuclear thioldisulfide redox states involves both the elimination of oxidants to prevent oxidation and the reduction of oxidized thiols to restore function. These processes depend on the common thiol reductants, glutathione (GSH) and thioredoxin-1 (Trx1). Recent evidence shows that these systems are controlled independent of the cytoplasmic counterparts. In addition, the GSH and Trx1 couples are not in redox equilibrium, indicating that these reductants have nonredundant functions in their support of proteins involved in transcriptional regulation, nuclear protein trafficking, and DNA repair. Specific isoforms of glutathione peroxidases, glutathione Stransferases, and peroxiredoxins are enriched in nuclei, further supporting the interpretation that functions of the thiol-dependent systems in nuclei are at least quantitatively distinct, and probably also qualitatively distinct, from similar processes in the cytoplasm. Elucidation of the distinct nuclear functions and regulation of the thiol redox pathways in nuclei can be expected to improve understanding of nuclear processes and also to provide the basis for novel approaches to treat aging and disease processes associated with oxidative stress in the nuclei. Antioxid. Redox Signal. 13, 489-509.

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Section: Distribution Of Redox Systems In Nucleimentioning

confidence: 79%

Section: Distribution Of Redox Systems In Nucleimentioning

confidence: 83%

Redox Control Systems in the Nucleus: Mechanisms and Functions

Jones

2010

Antioxidants & Redox Signaling

176

125

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“…GSTs protect against DNA damage-induced apoptosis by scavenging the formation of lipid-peroxide-modified DNA on oxidative stress. 68 Mitochondrial DNA damage is also modulated by GSH which reduces its susceptibility to oxidant-induced damage and apoptosis. 69 DNA cross-linker agents, such as cisplatin, have been reported to induce apoptosis paralleled by GSH depletion.…”

Section: Figure 1 Apoptotic Signaling Pathways (See Text For Further mentioning

confidence: 99%

Apoptosis and glutathione: beyond an antioxidant

2009

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Apoptosis is a conserved homeostatic process critical for organ and tissue morphogenesis, development, and senescence. This form of programmed cell death also participates in the etiology of several human diseases including cancer, neurodegenerative, and autoimmune disorders. Although the signaling pathways leading to the progression of apoptosis have been extensively characterized, recent studies highlight the regulatory role of changes in the intracellular milieu (permissive apoptotic environment) in the efficient activation of the cell death machinery. In particular, glutathione (GSH) depletion is a common feature of apoptotic cell death triggered by a wide variety of stimuli including activation of death receptors, stress, environmental agents, and cytotoxic drugs. Although initial studies suggested that GSH depletion was only a byproduct of oxidative stress generated during cell death, recent discoveries suggest that GSH depletion and post-translational modifications of proteins through glutathionylation are critical regulators of apoptosis. Here, we reformulate these emerging paradigms into our current understanding of cell death mechanisms. Apoptosis or programmed cell death is a ubiquitous homeostatic process involved in numerous biological systems. Under physiological conditions it is critical not only in the turnover of cells in tissues but also during normal development and senescence. Moreover, its deregulation has been widely observed to occur as either a cause or consequence of distinct pathologies including cancer, autoimmune, and neurodegenerative diseases. Apoptosis is a highly organized program induced by a myriad of stimuli that are characterized by the progressive activation of precise pathways leading to specific biochemical and morphological alterations in individual cells without involving an inflammatory response. Early stages of apoptosis are characterized by initiator caspase activation, cell shrinkage, loss of plasma membrane lipid asymmetry, and chromatin condensation. The execution phase of apoptosis is characterized by activation of executioner caspases and endonucleases, apoptotic body formation, and cell fragmentation 1 (Figure 1). Interestingly, recent studies have shown that changes in the intracellular milieu of the cells, such as alterations in the redox environment, are important regulators of the progression to apoptosis. 2 These discoveries have lead to the concept of a permissive apoptotic environment necessary for the activation of the proper signaling pathways regulating apoptosis. Glutathione (GSH) depletion is an early hallmark in the progression of cell death in response to a variety of apoptotic stimuli in numerous cell types 3,4 (Figure 2), although the exact role of GSH depletion in apoptosis is still controversial. We review recent data that show new insights into the understanding of the causes and consequences that alterations in the redox environment of the cell have on apoptosis.The Role of GSH in the Regulation of Apoptosis GSH synthesis, depletion, and apopt...

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“…Intracellular redox state is tightly controlled and is vitally important to cell survival and proper functioning. [15][16][17] Oxidative stress, resulting from an increase in the level of intracellular reactive oxygen species (ROS), is known to alter cellular redox state and induce apoptosis, leading to cell death. 17,18 Changes to redox state can also alter gene expression, 16 cellular metabolism and the post-translational modification of proteins.…”

Section: Introductionmentioning

confidence: 99%

“…[15][16][17] Oxidative stress, resulting from an increase in the level of intracellular reactive oxygen species (ROS), is known to alter cellular redox state and induce apoptosis, leading to cell death. 17,18 Changes to redox state can also alter gene expression, 16 cellular metabolism and the post-translational modification of proteins. 19 Glutathione, a cysteine-containing non-protein thiol, contains reducing and nucleophilic properties and is the major regulator of intracellular redox status in mammalian cells.…”

Section: Introductionmentioning

confidence: 99%

Short-chain fatty acid modulation of apoptosis in the kato III human gastric carcinoma cell line

Matthews¹,

Howarth²,

Butler³

2007

Cancer Biology & Therapy

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The short-chain fatty acid (SCFA) butyrate is known to induce apoptosis in colon cancer cells in vitro and in vivo, however, its mode of action is poorly defined, whilst less is known regarding the effects of the SCFA propionate. This study investigated the potential for butyrate and propionate to alter cell viability, cell cycle regulation and intracellular protective mechanisms in a human gastric cancer cell line (Kato III). Kato III cells were incubated with butyrate or propionate for 24, 48 and 72 hr. At each time point, cells were assessed for the induction of apoptosis and cell cycle alterations using flow cytometry. Oxidative pentose pathway (OPP) activity and glutathione (GSH) availability were also measured as an index of intracellular protection. Butyrate and propionate differentially induced apoptosis and necrosis in Kato III cells and arrested cells in the G 2 -M phase. OPP activity was significantly increased by both SCFAs although butyrate induced a 10-fold greater increase than propionate. GSH availability was significantly decreased in Kato III cells by butyrate and propionate. These findings demonstrate that butyrate and propionate induce apoptosis and cell cycle alterations in Kato III gastric cancer cells. Moreover, the effects of butyrate were significantly greater than propionate. We propose that alterations to intracellular redox state and GSH availability play an important role in SCFA-mediated cell death in this cell type. The inclusion of butyrate and propionate as adjunctive cancer therapies has the potential to enhance the efficacy of current chemotherapeutics in the treatment of gastric cancer.

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Nuclear glutathione S-transferase π prevents apoptosis by reducing the oxidative stress-induced formation of exocyclic dna products

Cited by 50 publications

References 39 publications

Redox Control Systems in the Nucleus: Mechanisms and Functions

Redox Control Systems in the Nucleus: Mechanisms and Functions

Apoptosis and glutathione: beyond an antioxidant

Short-chain fatty acid modulation of apoptosis in the kato III human gastric carcinoma cell line

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