Inhibition of Apoptosis in Human Retinal Pigment Epithelial Cells Treated with Benzo(e)Pyrene, a Toxic Component of Cigarette Smoke

Mansoor, Saffar; Gupta, Neeraj; Patil, A. Jayaprakash; Estrago-Franco, M. F.; Ramírez, Claudio; Migon, R.; Sapkal, A. U.; Kuppermann, Baruch D.; Kenney, M. Cristina

doi:10.1167/iovs.09-4121

Cited by 36 publications

(27 citation statements)

References 54 publications

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“…In a study 42 focused on blood flow in contact with reactive surfaces, AOs inhibited platelet activation by specific interactions with target proteins. In a different study 43 that examined the effects of toxic elements in smoking benzo(e)pyrene [B(e)P], combinations of genistein, R, and memantine inhibitors reversed the decreased cell viability, activation of apoptosis markers (caspase‐3/7 and caspase‐9) and increased the production of ROS/reactive nitrogen species in B(e)P‐treated human adult retinal pigment epithelial cell‐19 cultures. These inhibitors could be beneficial against retinal diseases associated with the loss of retinal pigmented epithelial cells 43 …”

Section: Discussionmentioning

confidence: 99%

Antioxidants Counteract Nicotine and Promote Migration via RacGTP in Oral Fibroblast Cells

Miguel

Opperman

Allen

et al. 2010

Journal of Periodontology

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Treatment with AO combinations clearly counteracted the effects of nicotine by restoring and increasing cell-migration rates. We found the combination of PFR was the most effective in HGFs, whereas, RFT was the most effective combination in HPDL fibroblast. These results clearly demonstrate that PF, RFT, and PFR counteract the negative effects of nicotine on cultured oral fibroblasts via the RacGTP signal-transduction pathway.

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Section: Discussionmentioning

confidence: 99%

Antioxidants Counteract Nicotine and Promote Migration via RacGTP in Oral Fibroblast Cells

Miguel

Opperman

Allen

et al. 2010

Journal of Periodontology

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“…Purified rat RPE cells were seeded in DMEM supplemented with 10% FBS in 96-well plates with or without glass coverslips and incubated at 37°C and 5% CO 2 for 5 to 7 days. Antioxidants resveratrol, lutein, or trolox were used at 30 μM, 50 μM, and 20 μM, respectively, as these concentrations had previously been established to be effective but non-toxic for RPE cells in culture [15–17]. They were supplied in complete medium at day 3 and 5 or on day 6 before use of cells on day 7.…”

Section: Methodsmentioning

confidence: 99%

Dietary antioxidants prevent age-related retinal pigment epithelium actin damage and blindness in mice lacking αvβ5 integrin

Nandrot

Dun

et al. 2012

Free Radical Biology and Medicine

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In the aging human eye, oxidative damage and accumulation of pro-oxidant lysosomal lipofuscin cause functional decline of the retinal pigment epithelium (RPE), which contributes to age-related macular degeneration. In mice with an RPE-specific phagocytosis defect due to lack of αvβ5 integrin receptors, RPE accumulation of lipofuscin suggests that the age-related blindness we previously described in this model may also result from oxidative stress. Cellular and molecular targets of oxidative stress in the eye remain poorly understood. Here we identify actin among 4-hydroxynonenal (HNE) adducts formed specifically in β5−/− RPE but not neural retina with age. HNE modification directly correlated with loss of resistance of actin to detergent extraction, suggesting cytoskeletal damage in aging RPE. Dietary enrichment with natural antioxidants grapes or marigold extract containing macular pigments lutein/zeaxanthin was sufficient to prevent HNE-adduct formation, actin solubility, lipofuscin accumulation, and age-related cone and rod photoreceptor dysfunction in β5−/− mice. Acute generation of HNE-adducts directly destabilized actin but not tubulin cytoskeletal elements of RPE cells. These findings identify destabilization of the actin cytoskeleton as a consequence of physiological, sublethal oxidative burden of RPE cells in vivo that is associated with age-related blindness and that can be prevented by consuming an antioxidant-rich diet.

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“…In our previous study, ARPE-19 cells showed a concentration-dependent decrease in cell viability after exposure to B(e)p.[11] In addition, B(e)p promoted apoptosis through activation of multiple caspases, which could be inhibited by exposure to memantine, resveratrol and genistein. [13]…”

Section: Discussionmentioning

confidence: 99%

“…[12] Furthermore, the damaging effects of B(e)p can be partially reversed by pre-treatment with memantine, resveratrol and genistein. [13] B(e)p with its structure of five fused aromatic rings (PAH) with a high molecular weight[14] can be found in substances besides cigarette smoke including automobile exhaust, charcoal-broiled foods, and incomplete combustion of organic materials. [15]…”

Section: Introductionmentioning

confidence: 99%

Effects of Benzo(e)pyrene on reactive oxygen/nitrogen species and inflammatory cytokines induction in human RPE cells and attenuation by mitochondrial-involved mechanism

Estrago-Franco¹,

Moustafa²,

Riazi‐Esfahani³

et al. 2016

J Ophthalmic Vis Res

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Purpose:To identify inhibitors that could effectively lower reactive oxygen/nitrogen species (ROS/RNS), complement and inflammatory cytokine levels induced by Benzo(e)pyrene [B(e)p], an element of cigarette smoke, in human retinal pigment epithelial cells (ARPE-19) in vitro.Methods:ARPE-19 cells were treated for 24 hours with 200 μM, 100 μM, and 50 μM B(e)p or DMSO (dimethyl sulfoxide)-equivalent concentrations. Some cultures were pre-treated with ROS/RNS inhibitors (NG nitro-L-arginine, inhibits nitric oxide synthase; Apocynin, inhibits NADPH oxidase; Rotenone, inhibits mitochondrial complex I; Antimycin A, inhibits mitochondria complex III) and ROS/RNS levels were measured with a fluorescent H2 DCFDA assay. Multiplex bead arrays were used to measure levels of Interleukin-6 (IL-6), Interleukin-8 (IL-8), Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF), Transforming Growth Factor alpha (TGF-α) and Vascular Endothelial Growth Factor (VEGF). IL-6 levels were also measured by an enzyme-linked immunosorbent assay. Real-time qPCR analyses were performed with primers for C3 (component 3), CFH (inhibits complement activation), CD59 (inhibitor of the complement membrane attack complex (MAC)) and CD55/DAF (accelerates decay of target complement target proteins).Results:The ARPE-19 cultures treated with B(e)p showed significantly increased ROS/RNS levels (P < 0.001), which were then partially reversed by 6 μM Antimycin A (19%, P = 0.03), but not affected by the other ROS/RNS inhibitors. The B(e)p treated cultures demonstrated increased levels of IL-6 (33%; P = 0.016) and GM-CSF (29%; P = 0.0001) compared to DMSO-equivalent controls, while the expression levels for components of the complement pathway (C3, CFH, CD59 and CD55/DAF) were not changed.Conclusion:The cytotoxic effects of B(e)p include elevated ROS/RNS levels along with pro-inflammatory IL-6 and GM-CSF proteins. Blocking the Qi site of cytochrome c reductase (complex III) with Antimycin A led to partial reduction in B(e)p induced ROS production. Our findings suggest that inhibitors for multiple pathways would be necessary to protect the retinal cells from B(e)p induced toxicity.

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Inhibition of Apoptosis in Human Retinal Pigment Epithelial Cells Treated with Benzo(e)Pyrene, a Toxic Component of Cigarette Smoke

Abstract: Genistein, resveratrol, and memantine can reverse the apoptosis and oxidant production generated by B(e)P, a toxic element of smoking. These inhibitors may be beneficial against retinal diseases associated with the loss of RPE cells.

Cited by 36 publications

References 54 publications

Antioxidants Counteract Nicotine and Promote Migration via RacGTP in Oral Fibroblast Cells

Antioxidants Counteract Nicotine and Promote Migration via RacGTP in Oral Fibroblast Cells

Dietary antioxidants prevent age-related retinal pigment epithelium actin damage and blindness in mice lacking αvβ5 integrin

Effects of Benzo(e)pyrene on reactive oxygen/nitrogen species and inflammatory cytokines induction in human RPE cells and attenuation by mitochondrial-involved mechanism

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