Graded sensitiveness of the various retinal neuron populations on the glyoxal-mediated formation of advanced glycation end products and ways of protection

Reber, Friedemann; Geffarth, Romy; Kasper, Michael; Reichenbach, Andreas; Schleicher, Erwin; Siegner, Axel; Funk, Richard

doi:10.1007/s00417-002-0528-1

Cited by 31 publications

(20 citation statements)

References 45 publications

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“…For those genes whose expression has previously been reported to be induced by AGEs, we observed similar results, even though the cell type was different. For example, AGEs have been reported to down-regulate Bcl-2 in retinal pigment epithelial cell and pericytes (39,53) and to up-regulate bax mRNA levels in mesangial cells and retinal neurons (54,55). Similar down-regulation of bcl-2 and upregulation of bax were found in AGE-stimulated fibroblasts.…”

Section: Discussionmentioning

confidence: 83%

Advanced Glycation End Products Enhance Expression of Pro-apoptotic Genes and Stimulate Fibroblast Apoptosis through Cytoplasmic and Mitochondrial Pathways

Alikhani

Boyd

et al. 2005

Journal of Biological Chemistry

193

121

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Both aging and diabetes are characterized by the formation of advanced glycation end products (AGEs). Both exhibit other similarities including deficits in wound healing that are associated with higher rates of fibroblast apoptosis. In order to investigate a potential mechanism for enhanced fibroblast apoptosis in diabetes and aged individuals, experiments were carried out to determine whether the predominant advanced glycation end product in skin, N-⑀-(carboxymethyl) lysine (CML)-collagen, could induce fibroblast apoptosis. In vivo experiments established that CML-collagen but not unmodified collagen induced fibroblast apoptosis and that apoptosis was dependent upon caspase-3, -8, and -9 activity. In vitro experiments demonstrated that CMLcollagen but not control collagen induced a time-and dose-dependent increase in fibroblast apoptosis. By use of blocking antibodies, apoptosis was shown to be mediated through receptor for AGE signaling. AGE-induced apoptosis was largely dependent on the effector caspase, caspase-3, which was activated through both cytoplasmic (caspase-8-dependent) and mitochondrial (caspase-9) pathways. CML-collagen had a global effect of enhancing mRNA levels of pro-apoptotic genes that included several classes of molecules including ligands, receptors, adaptor molecules, mitochondrial proteins, and others. However, the pattern of expression was not identical to the pattern of apoptotic genes induced by tumor necrosis factor ␣.

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Section: Discussionmentioning

confidence: 83%

Advanced Glycation End Products Enhance Expression of Pro-apoptotic Genes and Stimulate Fibroblast Apoptosis through Cytoplasmic and Mitochondrial Pathways

Alikhani

Boyd

et al. 2005

Journal of Biological Chemistry

193

121

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“…Glycation of vitreous collagen was also observed in human donor eyeballs (Sulochana et al, 2003). In addition, studies using anti-AGE agents further support the role of AGE in diabetic retinopathy Chappey etal., 1997;Reber et al, 2003). AGE have also been linked to the changes associated with diabetic keratopathy through their effect in reducing corneal epithelial cell adhesion (Matsumoto et al, 1997).…”

Section: Glycationmentioning

confidence: 99%

Gluco-Oxidation of Proteins in Etiology of Diabetic Retinopathy

Khan¹,

Banga²,

Khan³

2012

Diabetic Retinopathy

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“…In cortical neurons, nicotinamide antagonizes cell injury during free radical generating toxins such as tertiary butylhydroperoxide [76]. Nicotinamide also can protect both rod and cone photoreceptor cells against N-methyl-N-nitrosourea toxicity [138,139] as well as against glycation end products in all layers of the retina [140]. In animal studies, nicotinamide prevents neuronal degeneration against trauma [141], axonal degeneration [10], oxidative stress [13,24,26,29,39,75], cerebral ischemia [142][143][144], and spinal cord injury [145,146].…”

Section: Nicotinamide and Cellular Lifementioning

confidence: 99%

Cell Life Versus Cell Longevity: The Mysteries Surrounding the NAD+ Precursor Nicotinamide

Chong²,

Maiese³

2006

CMC

115

167

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Nicotinamide, the amide form of niacin (vitamin B 3 ), is the precursor for the coenzyme β-nicotinamide adenine dinucleotide (NAD + ) and plays a significant role during the enhancement of cell survival as well as cell longevity. Yet, these abilities of nicotinamide appear to be diametrically opposed. Here we describe the development of nicotinamide as a novel agent that is critical for modulating cellular metabolism, plasticity, longevity, and inflammatory microglial function as well as for influencing cellular life span. The capacity of nicotinamide to govern not only intrinsic cellular integrity, but also extrinsic cellular inflammation rests with the modulation of a host of cellular targets that involve mitochondrial membrane potential, poly(ADP-ribose) polymerase, protein kinase B (Akt), Forkhead transcription factors, Bad, caspases, and microglial activation. Further knowledge acquired in regards to the ability of nicotinamide to foster cellular survival and regulate cellular lifespan should significantly promote the development of therapies against a host of disorders, such as aging, Alzheimer's disease, diabetes, cerebral ischemia, Parkinson's disease, and cancer. KeywordsAkt; Alzheimer's disease; apoptosis; caspases; diabetes; erythropoietin; Huntington's disease; microglia; NAD + ; Parkinson's disease; stroke; vitamin B 3 NICOTINAMIDE, NAD + PRECURSOR, AND CELLULAR METABOLISMAs the amide form of niacin or vitamin B 3 , nicotinamide is the precursor for the coenzyme β-nicotinamide adenine dinucleotide (NAD + ) and is essential for the synthesis of nicotinamide adenine dinucleotide phosphate (NADP + ) [1,2]. Nicotinamide and nicotinic acid can be obtained either through synthesis in the body or through a dietary source [3]. The predominant form of niacin in dietary plant sources is nicotinic acid that is rapidly absorbed through the gastrointestinal epithelium. Nicotinamide is formed through the conversion of nicotinic acid in the liver or through the hydrolysis of NAD + . Once nicotinamide is obtained in the body, it is utilized to synthesize NAD + [4].Nicotinamide through NAD + plays a critical physiological role in cellular metabolism and can be directly utilized by cells to synthesize NAD + [4]. Nicotinamide also participates in energy metabolism through the tricarboxylic acid cycle by utilizing NAD + in the mitochondrial respiratory electron transport chain for the production of ATP, DNA synthesis, and DNA repair *Address correspondence to this author at the Department of Neurology, 8C-1 UHC, Wayne State University School of Medicine, 4201 St. Antoine, Detroit, MI 48201, USA; Fax: 313-966-0486; E-mail: kmaiese@med.wayne.edu. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript [5][6][7]. Furthermore, nicotinamide can significantly increase NAD + levels in vulnerable regions of the ischemic brain, suggesting that nicotinamide may offer cytoprotection of injured tissue through the maintenance of NAD + levels [8]. Administration of nicotinamide can signif...

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Graded sensitiveness of the various retinal neuron populations on the glyoxal-mediated formation of advanced glycation end products and ways of protection

Cited by 31 publications

References 45 publications

Advanced Glycation End Products Enhance Expression of Pro-apoptotic Genes and Stimulate Fibroblast Apoptosis through Cytoplasmic and Mitochondrial Pathways

Advanced Glycation End Products Enhance Expression of Pro-apoptotic Genes and Stimulate Fibroblast Apoptosis through Cytoplasmic and Mitochondrial Pathways

Gluco-Oxidation of Proteins in Etiology of Diabetic Retinopathy

Cell Life Versus Cell Longevity: The Mysteries Surrounding the NAD+ Precursor Nicotinamide

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