Inhibitors of Inducible Nitric Oxide Synthase Prevent Damage to Human Lens Epithelial Cells Induced by Interferon-Gamma and Lipopolysaccharide

Nagai, Noriaki; Liu, Ying; Fukuhata, Takashi; Ito, Yoshimasa

doi:10.1248/bpb.29.2077

Cited by 13 publications

(14 citation statements)

References 31 publications

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“…Indeed, high levels of iNOS mRNA and iNOS protein expression have been found in cataractous lenses, and oral administration of aminoguanidine, a specific iNOS inhibitor, markedly suppressed or prevented lens opacification (54,55). Carnosine is also present in the eye lenses at a high level (56,57); therefore, our result supports the hypothesis that a possible decrease during aging, as it is known in the muscle (58), could contribute to age-related cataractogenesis.…”

Section: Discussionsupporting

confidence: 82%

Protective Effects of l- and d-Carnosine on α-Crystallin Amyloid Fibril Formation: Implications for Cataract Disease

et al. 2009

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Mildly denaturing conditions induce bovine alpha-crystallin, the major structural lens protein, to self-assemble into fibrillar structures in vitro. The natural dipeptide l-carnosine has been shown to have potential protective and therapeutic significance in many diseases. Carnosine derivatives have been proposed as potent agents for ophthalmic therapies of senile cataracts and diabetic ocular complications. Here we report the inhibitory effect induced by the peptide (l- and d-enantiomeric form) on alpha-crystallin fibrillation and the almost complete restoration of the chaperone activity lost after denaturant and/or heat stress. Scanning force microscopy (SFM), thioflavin T, and a turbidimetry assay have been used to determine the morphology of alpha-crystallin aggregates in the presence and absence of carnosine. DSC and a near-UV CD assay evidenced that the structural precursors of amyloid fibrils are polypeptide chain segments that lack stable structural elements. Moreover, we have found a disassembling effect of carnosine on alpha-crystallin amyloid fibrils. Finally, we show the ability of carnosine to restore most of the lens transparency in organ-cultured rat lenses exposed to similar denaturing conditions that were used for the in vitro experiments.

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Section: Discussionsupporting

confidence: 82%

Protective Effects of l- and d-Carnosine on α-Crystallin Amyloid Fibril Formation: Implications for Cataract Disease

et al. 2009

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“…Nitric oxide donors also lead to decreases in ATP and GSH levels in the lens in organ culture (166). Treatment of the human lens epithelial cell line, SRA 01/04, with interferon-␥ and LPS leads to iNOS expression, a decrease in ATP levels, and an increase in Ca 2ϩ -ATPase activity, effects that are attenuated by NOS inhibitors (73,104).…”

Section: Nitrogen Oxides In the Lens In Relation To Connexins And Catmentioning

confidence: 99%

Oxidative Stress, Lens Gap Junctions, and Cataracts

Berthoud

Beyer

2009

Antioxidants & Redox Signaling

214

141

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The eye lens is constantly subjected to oxidative stress from radiation and other sources. The lens has several mechanisms to protect its components from oxidative stress and to maintain its redox state, including enzymatic pathways and high concentrations of ascorbate and reduced glutathione. With aging, accumulation of oxidized lens components and decreased efficiency of repair mechanisms can contribute to the development of lens opacities or cataracts. Maintenance of transparency and homeostasis of the avascular lens depend on an extensive network of gap junctions. Communication through gap junction channels allows intercellular passage of molecules (up to 1 kDa) including antioxidants. Lens gap junctions and their constituent proteins, connexins (Cx43, Cx46, and Cx50), are also subject to the effects of oxidative stress. These observations suggest that oxidative stress-induced damage to connexins (and consequent altered intercellular communication) may contribute to cataract formation. Antioxid. Redox Signal. 11, 339-353. 339The Eye Lens

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“…* p<0.01 vs normal ZL rats the vitreous body was elevated in diabetic retinopathy, endotoxin-induced uveitis and traumatic cataract [31][32][33]. Furthermore, it has been shown that the apoptosis of human LECs stimulated by LPS and interferon-γ is accompanied by the induction of iNOS [34]. A nitric oxide synthase inhibitor attenuates cataract formation when exposed to high levels of glucose in vitro.…”

Section: Discussionmentioning

confidence: 99%

Lens epithelial cell apoptosis initiates diabetic cataractogenesis in the Zucker diabetic fatty rat

Kim

Sohn

et al. 2010

Graefes Arch Clin Exp Ophthalmol

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Inhibitors of Inducible Nitric Oxide Synthase Prevent Damage to Human Lens Epithelial Cells Induced by Interferon-Gamma and Lipopolysaccharide

Abstract: We previously found that Ca 2؉ concentrations, inducible nitric oxide synthase (iNOS) mRNA, and protein expression in lenses of the Shumiya cataract rat (SCR) increase with the development of cataracts. In this study, we investigated the change in Ca

Cited by 13 publications

References 31 publications

Protective Effects of l- and d-Carnosine on α-Crystallin Amyloid Fibril Formation: Implications for Cataract Disease

Protective Effects of l- and d-Carnosine on α-Crystallin Amyloid Fibril Formation: Implications for Cataract Disease

Oxidative Stress, Lens Gap Junctions, and Cataracts

Lens epithelial cell apoptosis initiates diabetic cataractogenesis in the Zucker diabetic fatty rat

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