Nitric oxide is a signaling molecule that regulates gene expression
ABSTRACT Nitric oxide (NO) is a dynamic and bioreactive molecule that can both participate in and inhibit the genesis of disease. Its ability to have an impact on a wide range of physiological events stems from its capacity to reversibly alter the expression of specific genes and the activities of a wide range of proteins and signaling pathways. Yet, NO* remains an enigmatic molecule. Recently developed technologies, including gene-chips, two-dimensional electrophoresis, RNA interference, matrix-assisted laser desorption ionization (MALDI)-TOF (time-of-flight) mass spectrometry, and protein arrays will allow us to better understand how NO* and associated reactive nitrogen species (RNS) regulate both physiology and disease states, toward the development of treatments using NO* synthase inhibitors or NO* donors.
SourceAvailable from: Kylie J Mansfield[Show abstract] [Hide abstract]
ABSTRACT: Nitric oxide (NO) is capable of promoting either cell death or cell survival depending on cell type and experimental conditions. In this study, the possible effects of NO on the viability of lens epithelial cells were investigated in an explant model used previously to identify cellular changes associated with posterior capsule opacification following cataract surgery. Rat lens epithelial explants prepared from weanling rats were cultured in a serum-free medium for five days with or without the addition of the nitric oxide synthase inhibitor, L-N(omega)-nitro-L-arginine methyl ester (L-NAME), using the inactive enantiomer D-NAME as a control. Alternatively, explants were cultured for nine days with or without the NO donor, sodium nitroprusside. Explants were assessed morphologically and immunohistochemically or by determining DNA content. In the presence of L-NAME but not in controls, progressive rounding up and detachment of cells from the lens capsule occurred, leading to extensive cell loss. Affected cells showed apoptosis-like cell-surface blebbing and nuclear fragmentation. Conversely, inclusion of sodium nitroprusside suppressed the morphological changes and spontaneous cell loss that occurred when sparsely covered explants were cultured for nine days, increased cell coverage fourfold during that period, and prevented the expression of the transdifferentiation markers alpha-smooth muscle actin and fibronectin. In addition, whereas L-NAME exacerbated cell loss induced by culturing with 50 pg/ml transforming growth factor-beta2, sodium nitroprusside offered protection. This study points to a previously unidentified role for NO as an endogenously produced survival factor for lens epithelial cells, raising the possibility of using NO deprivation as a means of removing residual lens cells following cataract surgery and thereby preventing posterior capsule opacification.Molecular vision 05/2008; 14:983-91. · 2.25 Impact Factor
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ABSTRACT: Damage of lens epithelial cells (LECs) has been implicated in cataract formation. The aim of this study was to investigate the protective effect of KIOM-79, a combination of four plant extracts, on LECs. We examined the levels of advanced glycation end products (AGEs), nuclear factor-kappaB (NF-κB) activation and inducible nitric oxide synthase (iNOS) expression in LECs during cataract development using the Zucker diabetic fatty (ZDF) rat, an animal model of type 2 diabetes. KIOM-79 was orally administered by gavage to ZDF rats once a day for 13 weeks. Apoptosis was detected by TUNEL assay, and NF-κB activation and iNOS expression were studied by southwestern histochemistry and immunohistochemistry, respectively. In diabetic cataractous lenses, TUNEL-positive LECs were markedly increased 20-fold, and AGEs were highly accumulated (2.7-fold) in LECs. In addition, both NF-κB activation, and iNOS expression were significantly enhanced 3- to 5-fold, respectively, compared to levels found in normal ZL rats. However, the administration of KIOM-79 delayed the development of diabetic cataracts and prevented LEC apoptosis (70%) through the inhibition of AGEs, NF-κB-activation and iNOS expression. These observations suggest that KIOM-79 is useful in inhibiting diabetic cataractogenesis and acts through an antiapoptotic mechanism to protect LECs from injury.Evidence-based Complementary and Alternative Medicine 01/2011; 2011. DOI:10.1155/2011/717921 · 2.18 Impact Factor
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ABSTRACT: The role of inflammation in carcinogenesis has been extensively investigated and well documented. Many biochemical processes that are altered during chronic inflammation have been implicated in tumorigenesis. These include shifting cellular redox balance toward oxidative stress; induction of genomic instability; increased DNA damage; stimulation of cell proliferation, metastasis, and angiogenesis; deregulation of cellular epigenetic control of gene expression; and inappropriate epithelial-to-mesenchymal transition. A wide array of proinflammatory cytokines, prostaglandins, nitric oxide, and matricellular proteins are closely involved in premalignant and malignant conversion of cells in a background of chronic inflammation. Inappropriate transcription of genes encoding inflammatory mediators, survival factors, and angiogenic and metastatic proteins is the key molecular event in linking inflammation and cancer. Aberrant cell signaling pathways comprising various kinases and their downstream transcription factors have been identified as the major contributors in abnormal gene expression associated with inflammation-driven carcinogenesis. The posttranscriptional regulation of gene expression by microRNAs also provides the molecular basis for linking inflammation to cancer. This review highlights the multifaceted role of inflammation in carcinogenesis in the context of altered cellular redox signaling.Free Radical Biology and Medicine 03/2012; 52(9):2013-37. DOI:10.1016/j.freeradbiomed.2012.02.035 · 5.71 Impact Factor