Nicotinamide induces apoptosis and reduces collagen I and pro-inflammatory cytokines expression in rat hepatic stellate cells

Traister, Alexandra; Breitman, Igal; Bar-Lev, Ella; Zvibel, Isabel; Harel, Avikam; Halpern, Zamir; Oren, Ran

doi:10.1080/00365520510023341

Cited by 32 publications

(30 citation statements)

References 22 publications

(25 reference statements)

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“…Under other conditions, nicotinamide has been described as an agent that limits cell growth and promotes cell injury. Nicotinamide in the presence of transforming growth factor β-1 can block hepatic cell proliferation and lead to apoptosis with caspase 3 activation [274]. During moderate temperature hyperthermia or carbogen breathing, nicotinamide also can result in enhanced solid tumor radiosensitivity and assist with tumor load reduction [275].…”

Section: Controversies and Challenges For Clinical Applicationsmentioning

confidence: 99%

Triple play: Promoting neurovascular longevity with nicotinamide, WNT, and erythropoietin in diabetes mellitus

Maiese

2008

Biomedicine & Pharmacotherapy

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SummaryOxidative stress is a principal pathway for the dysfunction and ultimate destruction of cells in the neuronal and vascular systems for several disease entities, non promoting the ravages of oxidative stress to any less of a degree than diabetes mellitus. Diabetes mellitus is increasing in incidence as a result of changes in human behavior that relate to diet and daily exercise and is predicted to affect almost 400 million individuals worldwide in another two decades. Furthermore, both type 1 and type 2 diabetes mellitus can lead to significant disability in the nervous and cardiovascular systems, such as cognitive loss and cardiac insufficiency. As a result, innovative strategies that directly target oxidative stress to preserve neuronal and vascular longevity could offer viable therapeutic options to diabetic patients in addition to more conventional treatments that are designed to control serum glucose levels. Here we discuss the novel application of nicotinamide, Wnt signaling, and erythropoietin that modulate cellular oxidative stress and offer significant promise for the prevention of diabetic complications in the nervous and vascular systems. Essential to this process is the precise focus upon diverse as well as common cellular pathways governed by nicotinamide, Wnt signaling, and erythropoietin to outline not only the potential benefits, but also the challenges and possible detriments of these therapies. In this way, new avenues of investigation can hopefully bypass toxic complications, or at the very least, avoid contraindications that may limit care and offer both safe and robust clinical treatment for patients.

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Section: Controversies and Challenges For Clinical Applicationsmentioning

confidence: 99%

Triple play: Promoting neurovascular longevity with nicotinamide, WNT, and erythropoietin in diabetes mellitus

Maiese

2008

Biomedicine & Pharmacotherapy

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“…Nicotinamide also can alter major histocompatibility complexes [123], inhibit intracellular adhesion molecule expression [124], and modulate the production of TNF in vascular cells [123]. In systems that involve hepatic cells, nicotinamide can reduce expression of several cytokines that include transforming growth factor (TGF) β2, IL-1β, TNF-α, and macrophage chemotactic protein-1 [125]. Nicotinamide also may be a viable option for the treatment of inflammatory mechanisms that lead to arthritis, such as the inhibition of collagen II expression [126].…”

mentioning

confidence: 99%

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

Chong²,

Maiese³

2006

CMC

113

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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“…A necrose maciça decorrente da exposição a agentes químicos ou virais também são um estímulo para o início da proliferação, e essa resposta é essencial para a sobrevivência (Fausto e Webber, 1994 Quando ativadas, são altamente quimiotáticas (Gutierrez-Reyes et al, 2007;Traister et al, 2005).…”

Section: Descriptorsunclassified

“…Pacientes com cirrose devem receber vitaminas do complexo B por via perenteral (Brunneto et al, 2007). A nicotinamida mostrou ser um potencial agente antifibrigênico (Traister et al, 2005 (Low et al, 2004). Para ter o efeito tóxico ao fígado, a tiocetamida necessita ser bioativada pelo CYP2E1 para formar dois metabólitos: sulfóxido de tiocetamida (TASO) e o dióxido de tiocetamida (TASO 2 ) (Ramaiah et al, 2001).…”

Section: Revisão De Literaturaunclassified

“…Por outro lado, durante a regeneração hepática decorrente da HP, ocorre um aumento da expressão de mRNA TGF-β1, que é um conhecido inibidor da proliferação de hepatócitos, talvez para previnir um crescimento descontrolado e encerrar o precesso regenerativo. (Braun et al, 1988;Stalnikowitz e Weissbrod, 2003;Traister et al, 2005) O colageno tipo I, principal componente produzido durante a fibrogênese hepática, é o produto de dois genes, os Colα -1 e -2. Além do TGF-β1, outras substâncias podem aumentar a expressão desses genes durante a injúria, principalmente a IL-6 e o TIMP1.…”

Section: Revisão De Literaturaunclassified

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Efeito da hepatectomia parcial associada à administração de fatores nutricionais hepatotróficos sobre a morfologia, função e expressão de genes pró-fibróticos na cirrose hepática em ratos Wistar induzida por tiocetamida

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Nicotinamide induces apoptosis and reduces collagen I and pro-inflammatory cytokines expression in rat hepatic stellate cells

Abstract: The in vitro effect of nicotinamide on activation and proliferation of hepatic stellate cells suggests that nicotinamide may have a potential beneficial role in attenuation of liver fibrogenesis.

Cited by 32 publications

References 22 publications

Triple play: Promoting neurovascular longevity with nicotinamide, WNT, and erythropoietin in diabetes mellitus

Triple play: Promoting neurovascular longevity with nicotinamide, WNT, and erythropoietin in diabetes mellitus

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

Efeito da hepatectomia parcial associada à administração de fatores nutricionais hepatotróficos sobre a morfologia, função e expressão de genes pró-fibróticos na cirrose hepática em ratos Wistar induzida por tiocetamida

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