tert.-Butyl hydroperoxide-mediated DNA base damage in cultured mammalian cells

Altman, Steven; Zastawny, Tomasz H.; Randers, Lisa; Lin, Zhanglin; Lumpkin, Janice A.; Remacle, José; Dizdaroğlu, Miral; Rao, Govind

doi:10.1016/0027-5107(94)90165-1

Cited by 66 publications

(25 citation statements)

References 33 publications

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“…5) t-BHP causes leakage of lactate dehydrogenase (LDH) and formation of malondialdehyde (MDA) in hepatocytes, 6) and also mediates DNA base damage in mammalian cells. 7) These phenomena are similar to the oxidative stress occurring in the cell and/or tissue.…”

Section: 4)mentioning

confidence: 89%

Protective Effects of Panduratin A against Oxidative Damage of <i>tert</i>-Butylhydroperoxide in Human HepG2 Cells

Sohn

Han

Lee

et al. 2005

Biological & Pharmaceutical Bulletin

105

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Reactive oxygen species (ROS) act as subcellular messengers in such complex cellular processes as mitogenic signal transduction, gene expression, and regulation of cell proliferation.1) Excessive production of ROS may, however, cause oxidative stress, loss of cell function, and ultimately apoptosis or necrosis.2) Fortunately, cells possess antioxidant molecules which can neutralize ROS before they induce damage on vital components. However, oxidative stress occurs when antioxidant systems are overwhelmed by ROS. Oxidative stress is considered to play a prominent role in the causation of many diseases including aging, cardiovascular disease, cancer and liver injury. 3,4) tert-Butylhydroperoxide (t-BHP) is an organic hydroperoxidant that can be metabolized to free radical intermediates, which can subsequently initiate lipid peroxidation, affect cell integrity, and form covalent bonds with cellular molecules resulting in cell injury. 5) t-BHP causes leakage of lactate dehydrogenase (LDH) and formation of malondialdehyde (MDA) in hepatocytes, 6) and also mediates DNA base damage in mammalian cells. 7) These phenomena are similar to the oxidative stress occurring in the cell and/or tissue.Because of its unique metabolism and relationship to the gastrointestinal tract, the liver is an important target of the toxicity of drugs, xenobiotics, and oxidative stress. 8) Reactive oxygen species derived from chemicals or drugs exposed to liver cells seem to mediate liver injury, although the mechanisms of free radical toxicity are not well understood. 9)Therefore, primary importance is to understand the role of antioxidants which can reduce the oxidative stress induced by reactive intermediates from various chemicals and drugs. We have investigated hepatoprotective drugs, based on the measurement of cytotoxicity of t-BHP against human-liver-derived HepG2 cells. HepG2 cells have been suggested to be a useful in vitro model for investigation of the metabolism and toxicity of drugs compared with animal cells, since HepG2 cells retain many of the specialized functions which are characteristics of normal human hepatocytes, including the synthesis and secretion of plasma proteins. 10)Kaempferia pandurata ROXB. is a perennial herb of the family Zingiberaceae cultivated in some tropical countries, including Thailand and Indonesia. Its rhizome has been used as a food ingredient, an aphrodisiac, and a folk medicine for the treatment of colic disorder, fungal infections, dry cough, rheumatism, and muscular pains.11,12) Panduratin A (Fig. 1A) is a chalcone derivative isolated from K. pandurata. It was recently reported that panduratin A possessed significant topical anti-inflammatory activity in murine macrophages, 12) and in the TPA-induced ear edema in rats. 13)The objective of the current study was to examine the ability of panduratin A to protect hepatocytic injury induced by t-BHP and to characterize the mechanisms involved. For this purpose, we have studied the cell viability, lipid peroxidation, glutathione (GSH) level, and ROS le...

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Section: 4)mentioning

confidence: 89%

Protective Effects of Panduratin A against Oxidative Damage of <i>tert</i>-Butylhydroperoxide in Human HepG2 Cells

Sohn

Han

Lee

et al. 2005

Biological & Pharmaceutical Bulletin

105

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“…tBHP is a membrane penetrable alkyl hydroperoxide reagent widely used to induce oxidative stress in cells (51)(52)(53)(54). The toxicity of tBHP is attributed to the generation of butoxyl radicals due to the Fenton reaction which can subsequently initiate lipid peroxidation, modify cellular lipids and proteins ( Figures 9-11), affect cell integrity and signalling, and form covalent bonds with cellular molecules resulting in cell injury.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Oxidative Stress in HEK 293 Cells by the TCM Constituents Schisanhenol, Baicalein, Resveratrol or Crocetin and Two Defined Mixtures

et al. 2015

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-PURPOSE:Our working hypothesis is that single bioactive phytochemicals with antioxidant properties that are important constituents of Traditional Chinese Medicine (TCM) and their defined mixtures have potential as chemoprotective agents for chronic conditions characterized by oxidative and nitrosative stress, including Alzheimer's. Here we evaluate the ability of baicalein, crocetin, trans-resveratrol or schisanhenol and two defined mixtures of these TCM phytochemicals to attenuate the toxicity resulting from exposure to cell permeant t-butyl hydroperoxide (tBPH) in wild-type and bioengineered (to express choline acetyltransferase) HEK 293 cells. METHODS: Endpoints of tBHP-initiated oxidative and nitrosative stress in both types of HEK 293 cells and its attenuation by TCM constituents and mixtures included cytotoxicity (LDH release); depletion of intracellular glutathione (GSH); formation of S-glutathionylated proteins; oxidative changes to the disulfide proteome; and real-time changes in intracellular redox status. RESULTS: At low µM concentrations, each of the TCM constituents and mixtures effectively attenuated intracellular toxicity due to exposure of HEK 293 cells to 50 or 250 µM tBHP for 30 min to 3 h. Confocal microscopy of HEK 293 cells transfected with mutated green fluorescent protein (roGFP2) showed effective attenuation of tBHP oxidation by baicalein in real time. Three redox-regulated proteins prominent in the disulfide proteome of HEK 293 cells were identified by MALDI-TOF mass spectrometry. CONCLUSIONS: We conclude that single TCM chemicals and their simple mixtures have potential for use in adjunct chemoprotective therapy. Advantages of mixtures compared to single TCM constituents include the ability to combine compounds with varying molecular mechanisms of cytoprotection for enhanced biological activity; and to combine chemicals with complementary pharmacokinetic properties to increase half-life and prolong activity in vivo.

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“…The organic hydroperoxide t-BOOH has been shown to cause DNA damage in mammalian cells because it reacts with metals to generate tert-butoxyl radicals (Altman et al, 1994). DpsA-type proteins have previously been demonstrated to prevent iron-dependent hydroxy radical formation (Yamamoto et al, 2002) and in B. pseudomallei, DpsA conferred protection against t-BOOH ( Loprasert et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Quorum sensing regulates dpsA and the oxidative stress response in Burkholderia pseudomallei

et al. 2006

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Burkholderia pseudomallei is the causative agent of melioidosis, a fatal human tropical disease. The non-specific DNA-binding protein DpsA plays a key role in protecting B. pseudomallei from oxidative stress mediated, for example, by organic hydroperoxides. The regulation of dpsA expression is poorly understood but one possibility is that it is regulated in a cell population density-dependent manner via N-acylhomoserine lactone (AHL)-dependent quorum sensing (QS) since a lux-box motif has been located within the dpsA promoter region. Using liquid chromatography and tandem mass spectrometry, it was first established that B. pseudomallei strain PP844 synthesizes AHLs. These were identified as N-octanoylhomoserine lactone (C8-HSL), N-(3-oxooctanoyl)homoserine lactone (3-oxo-C8-HSL), N-(3-hydroxyoctanoyl)-homoserine lactone (3-hydroxy-C8-HSL), N-decanoylhomoserine lactone (C10-HSL), N-(3-hydroxydecanoyl) homoserine lactone (3-hydroxy-C10-HSL) and N-(3-hydroxydodecanoyl)homoserine lactone (3-hydroxy-C12-HSL). Mutation of the genes encoding the LuxI homologue BpsI or the LuxR homologue BpsR resulted in the loss of C8-HSL and 3-oxo-C8-HSL synthesis, demonstrating that BpsI was responsible for directing the synthesis of these AHLs only and that bpsI expression and hence C8-HSL and 3-oxo-C8-HSL production depends on BpsR. In bpsI, bpsR and bpsIR mutants, dpsA expression was substantially down-regulated. Furthermore, dpsA expression in Escherichia coli required both BpsR and C8-HSL. bpsIR-deficient mutants exhibited hypersensitivity to the organic hydroperoxide tert-butyl hydroperoxide by displaying a reduction in cell viability which was restored by provision of exogenous C8-HSL (bpsI mutant only), by complementation with the bpsIR genes or by overexpression of dpsA. These data indicate that in B. pseudomallei, QS regulates the response to oxidative stress at least in part via the BpsR/C8-HSL-dependent regulation of DpsA.

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tert.-Butyl hydroperoxide-mediated DNA base damage in cultured mammalian cells

Cited by 66 publications

References 33 publications

Protective Effects of Panduratin A against Oxidative Damage of <i>tert</i>-Butylhydroperoxide in Human HepG2 Cells

Protective Effects of Panduratin A against Oxidative Damage of <i>tert</i>-Butylhydroperoxide in Human HepG2 Cells

Attenuation of Oxidative Stress in HEK 293 Cells by the TCM Constituents Schisanhenol, Baicalein, Resveratrol or Crocetin and Two Defined Mixtures

Quorum sensing regulates dpsA and the oxidative stress response in Burkholderia pseudomallei

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