Involvement of reactive oxygen species in indomethacin-induced apoptosis of small intestinal epithelial cells

Omatsu, Tatsushi; Naito, Yuji; Handa, Osamu; Hayashi, Nakanobu; Mizushima, Katsura; Qin, Ying; Hirata, Ikuhiro; Adachi, Satoko; Okayama, Tetsuya; Kishimoto, Etsuko; Takagi, Tomohisa; Kokura, Satoshi; Ichikawa, Hiroshi; Yoshikawa, Toshikazu

doi:10.1007/s00535-008-2293-3

Cited by 54 publications

(47 citation statements)

References 7 publications

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“…A similar decrease in TEER has been reported in another study, where human embryonic stem cell (hESC)-derived RPE cells and ARPE-19 cells were exposed to hydrogen peroxide. 31,32 These results are also in agreement with a previous study performed in our laboratory using the ARPE-19.…”

Section: Discussionsupporting

confidence: 83%

“…To investigate the ability of NACA to preserve BRB function, membrane integrity after TBHP exposure was evaluated using dextran permeability and TEER assays. 31 NACA prevented TBHP-induced reduction in TEER, verifying its ability to protect cellular homeostasis and outer BRB integrity under severe oxidative stress conditions. A similar decrease in TEER has been reported in another study, where human embryonic stem cell (hESC)-derived RPE cells and ARPE-19 cells were exposed to hydrogen peroxide.…”

Section: Discussionmentioning

confidence: 99%

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The role of N-acetylcysteine amide in defending primary human retinal pigment epithelial cells against tert-butyl hydroperoxide- induced oxidative stress

Wang

Huang

Tobwala

et al. 2017

FRA

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INTRODUCTIONAge-related macular degeneration (AMD) accounts for 8.7% of blindness worldwide, and it is a leading cause of blindness in the United States among adults age 60 and older. [1][2][3] Globally, about 1 in 32 visual impairments and 1 in 15 cases of blindness are due to macular disease. 4 Dry AMD is a degenerative condition that begins in Bruch's membrane and progresses to the retinal pigment epithelium (RPE) and the overlying photoreceptors with loss of central vision. The RPE is a single layer of pigment cells lying between the photoreceptors and choriocapillaris. The functions of the RPE include light absorption, epithelial transport, phagocytosis, secretion, and immune modulation. All of these functions are important to maintaining and supporting the photoreceptors. High blood flow rate and high O 2 saturation in the choriocapillaris render the RPE more exposed to oxidative stress. 5Oxidative stress seems to play a major role in the pathogenesis of dry AMD and retinal degeneration, although the pathophysiology of dry AMD is complex. 5,6 The macula is subject to increased levels of photooxidative stress because of its elevated metabolic rate and high proportion of polyunsaturated fatty acids, which are highly susceptible to lipid peroxidation. As the RPE cells of the macula age, oxidation of lipids and other cellular components results in an accumulation of indigestible lipofuscin in the lysosomes. The accumulation of lipofuscin granules closely parallels drusen formation in time course and distribution in the retina. Oxidative damage to the mitochondrial DNA in RPE cells has also been implicated in the development of AMD. Levels of antioxidants in retinal tissue, in particular glutathione (GSH), decrease with aging, making the macula even more vulnerable to progressive oxidative damage. 7,8 Endogenous antioxidants, such as GSH, cannot be replaced directly. Instead, compounds that can easily enter cells and increase intracellular antioxidant levels are preferred. Dietary antioxidants have been shown to slow the progression of retinal degeneration and halt progression of AMD in human clinical trials.9,10 GSH and its amino acid precursors protect RPE cells from oxidative injury and oxidant-induced apoptosis in vitro. N-acetylcysteine amide (NACA), a GSH prodrug, is a promising candidate for use as an antioxidant-based treatment for AMD. It has demonstrated efficacy in numerous in vitro and animal models of other oxidative stress-related conditions, including drug-induced RPE damage and cataracts. [11][12][13][14][15] Our lab has demonstrated that NACA prevented retinal degeneration in vitro and in animal models.14 The immortalized ARPE-19 cell line was used as an in vitro model because primary human RPE cells were not available at the time. ROS generation and lipid peroxidation induced by tert-butyl hydroperoxide (TBHP) were reversed by pretreatment with NACA. NACA also protected against TBHP-induced cell damage by increasing cellular levels of GSH, and maintaining cellular integrity, as measured by tra...

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

The role of N-acetylcysteine amide in defending primary human retinal pigment epithelial cells against tert-butyl hydroperoxide- induced oxidative stress

Wang

Huang

Tobwala

et al. 2017

FRA

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“…This means that HSP70 can reduce oxidative stress and cell injury. Our group recently showed that ROS are involved in indomethacin-induced intestinal epithelial cell injury [23]. ROS are initiators of lipid peroxidation.…”

Section: Discussionmentioning

confidence: 99%

Heat-Shock Protein 70-Overexpressing Gastric Epithelial Cells Are Resistant to Indomethacin-Induced Apoptosis

et al. 2009

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Background/Aims: Protecting intestinal mucosa from nonsteroidal anti-inflammatory drugs is still an unsolved problem. It has been revealed that apoptosis in epithelial cells as a result of mitochondrial injury is an important pathogenesis in indomethacin-induced gastric mucosal injury. In this study, we revealed the effect of overexpressed heat-shock protein 70 (HSP70) in indomethacin-induced apoptosis and oxidative stress. Methods: HSP70-overexpressing rat gastric mucosal cells (7018-RGM-1 cells) and control cells (pBK-CMV-12 cells) were used and treated with 0–500 μM of indomethacin for 24 h. Cell viability and cytotoxity were measured by a WST-8 assay and a lactate dehydrogenase release assay, respectively. Apoptosis was observed by fluorescence microscopy staining with Hoechst 33342 and propidium iodide. The expression of Bcl-2 family proteins, activation of caspase-3, and 4-hydroxy-2-nonenal (4-HNE)-modified proteins were assessed by Western blot analysis. Results: Indomethacin caused apoptosis of gastric epithelial cells. The 7018-RGM-1 cells survived significantly after indomethacin treatment compared to the control cells. The increase in pro-apoptotic Bad proteins, the decrease in anti-apoptotic Bcl-2 proteins, and caspase activation were all suppressed in the 7018-RGM-1 cells. A lower level of indomethacin-induced 4-HNE-modification was detected in the 7018-RGM-1 cells than in the control cells. Conclusion: Overexpressed HSP70 may potentiate resistance to apoptosis and oxidative stress in indomethacin-induced gastric epithelial cell injury.

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“…We previously reported that cyclooxygenase (COX)-dependent and COX-independent pathways were involved in this phenomenon, and we found that indomethacin significantly induced reactive oxygen species (ROS) production in small intestinal epithelial cells through a COX-independent pathway [10].…”

Section: Introductionmentioning

confidence: 95%

Reactive oxygen species-quenching and anti-apoptotic effect of polaprezinc on indomethacin-induced small intestinal epithelial cell injury

et al. 2010

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Involvement of reactive oxygen species in indomethacin-induced apoptosis of small intestinal epithelial cells

Abstract: Taken together, reactive oxygen species production is one of the mechanisms by which indomethacin induced small intestinal injury.

Cited by 54 publications

References 7 publications

The role of N-acetylcysteine amide in defending primary human retinal pigment epithelial cells against tert-butyl hydroperoxide- induced oxidative stress

The role of N-acetylcysteine amide in defending primary human retinal pigment epithelial cells against tert-butyl hydroperoxide- induced oxidative stress

Heat-Shock Protein 70-Overexpressing Gastric Epithelial Cells Are Resistant to Indomethacin-Induced Apoptosis

Reactive oxygen species-quenching and anti-apoptotic effect of polaprezinc on indomethacin-induced small intestinal epithelial cell injury

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