Administration of nicotinamide does not increase platelet levels in mice

Konieczna, Iwona; Panuganti, Swapna; DeLuca, Teresa A.; Papoutsakis, E. T.; Eklund, Elizabeth A.; Miller, William M.

doi:10.1016/j.bcmd.2012.11.007

Cited by 11 publications

(6 citation statements)

References 24 publications

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“…Although NAM has been shown to increase the homing of haematopoietic progenitors and to enhance platelet production in vitro 239,240 , NAM supplementation does not enhance haematopoiesis in vivo 238,241 . These differences between the effects of NAM and NR may be due to the tissue-specific preferences for NAD + precursors.…”

Section: Nad(p)h-quinone Oxidoreductase 1 (Nqo1) Is An Antioxidantmentioning

confidence: 99%

NAD+ homeostasis in health and disease

et al. 2020

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AD, the first cofactor described, was discovered in 1906 (ref. 1 ), when it was observed that yeast juice separated into low-and high-molecular-weight fractions lost the capacity to perform alcoholic fermentation. However, addition of the lowmolecular-weight fraction to yeast accelerated the fermentation reaction, even if it was boiled beforehand. This observation suggested that a yet-unknown heat-stable factor present in the lowmolecular-weight fraction was required for fermentation. At that time, this factor was named 'cozymase' . Almost three decades later, the chemical composition of cozymase, comprising an adenine, a phosphate and a reducing-sugar group, was reported 2 . The actual function of NAD + , however, remained unclear until 1936, when cozymase was shown to be capable of transferring hydride between molecules with the nicotinamide base as its redox site 3 . This research on NAD + was rewarded by three Nobel prizes. In the early 2000s, interest in NAD + experienced a resurrection, after a novel role of NAD + as a cosubstrate for the sirtuin enzyme family, important regulators of longevity and metabolism, was discovered 4-6 .Brain 98 NMNaT3Testis 307 Intestine, spleen, brain, SM, lung, pancreas, blood, WaT 98,307

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Section: Nad(p)h-quinone Oxidoreductase 1 (Nqo1) Is An Antioxidantmentioning

confidence: 99%

NAD+ homeostasis in health and disease

et al. 2020

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“…We chose a NAD + -boosting strategy because it has been characterized as a means of activating the SIRT1 axis via the induction of the mitochondrial stress response in the context of aging, liver, and muscle regeneration (Imai et al, 2000;Belenky et al, 2007;Cantó et al, 2012;Mouchiroud et al, 2013;Zhang et al, 2016). Interestingly, the NAD + precursor nicotinamide (NAM) has been shown to increase the homing of hematopoietic progenitors and to enhance platelet formation in vitro (Giammona et al, 2009;Peled et al, 2012;Horwitz et al, 2014), but efforts to use NAM supplementation to enhance hematopoiesis in vivo have failed (Konieczna et al, 2013). Here we reveal the ability of a different NAD + -boosting agent, nicotinamide riboside (NR), to reduce mitochondrial potential in HSCs and enhance hematopoiesis in vivo via activation of autophagy, increased mitochondrial clearance, and increased proliferative asymmetry in LT-HSCs through the NR-Nrk1/2-NMN axis.…”

Section: Introductionmentioning

confidence: 99%

The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance

et al. 2019

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Graphical AbstractHighlights d Vitamin B3 analogs improve hematopoietic stem cell (HSC) and progenitor function d Nicotinamide riboside (NR) increases mitochondrial recycling in HSCs d In vitro NR exposure induces asymmetric mitochondrial distribution in dividing HSCs d NR dietary supplementation improves survival after HSC transplantation in mice SUMMARYIt has been recently shown that increased oxidative phosphorylation, as reflected by increased mitochondrial activity, together with impairment of the mitochondrial stress response, can severely compromise hematopoietic stem cell (HSC) regeneration. Here we show that the NAD + -boosting agent nicotinamide riboside (NR) reduces mitochondrial activity within HSCs through increased mitochondrial clearance, leading to increased asymmetric HSC divisions. NR dietary supplementation results in a significantly enlarged pool of progenitors, without concurrent HSC exhaustion, improves survival by 80%, and accelerates blood recovery after murine lethal irradiation and limiting-HSC transplantation. In immune-deficient mice, NR increased the production of human leucocytes from hCD34+ progenitors. Our work demonstrates for the first time a positive effect of NAD +boosting strategies on the most primitive blood stem cells, establishing a link between HSC mitochondrial stress, mitophagy, and stem-cell fate decision, and unveiling the potential of NR to improve recovery of patients suffering from hematological failure including post chemo-and radiotherapy.

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“…To our knowledge, the only derivative of vitamin B 3 tested thus far for its haematopoietic effects was nicotinamide. Although NA stimulated polyploidization of megakaryocytes in vitro, regular injections of this compound to C57Bl/6 mice did not result in an increase of the platelet counts in the blood 32 – 34 . Likewise, as reported by Fu and co-workers, prolonged survival of the lethally irradiated CD2F1 mice induced by application of a naturally occurring analogue of somatostatin (SOM230) was not associated with mitigation of the radiation-induced haematopoietic depression 29 .…”

Section: Discussionmentioning

confidence: 84%

A derivative of vitamin B3 applied several days after exposure reduces lethality of severely irradiated mice

Cheda

Nowosielska

Gębicki

et al. 2021

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Most, if not all, of the hitherto tested substances exert more or less pronounced pro-survival effects when applied before or immediately after the exposure to high doses of ionizing radiation. In the present study we demonstrate for the first time that 1-methyl nicotinamide (MNA), a derivative of vitamin B3, significantly (1.6 to 1.9 times) prolonged survival of BALB/c mice irradiated at LD30/30 (6.5 Gy), LD50/30 (7.0 Gy) or LD80/30 (7.5 Gy) of γ-rays when the MNA administration started as late as 7 days post irradiation. A slightly less efficient and only after the highest dose (7.5 Gy) of γ-rays was another vitamin B3 derivative, 1-methyl-3-acetylpyridine (1,3-MAP) (1.4-fold prolonged survival). These pro-survival effects did not seem to be mediated by stimulation of haematopoiesis, but might be related to anti-inflammatory and/or anti-thrombotic properties of the vitamin B3 derivatives. Our results show that MNA may represent a prototype of a radioremedial agent capable of mitigating the severity and/or progression of radiation-induced injuries when applied several hours or days after exposure to high doses of ionizing radiation.

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Administration of nicotinamide does not increase platelet levels in mice

Cited by 11 publications

References 24 publications

NAD+ homeostasis in health and disease

NAD+ homeostasis in health and disease

The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance

A derivative of vitamin B3 applied several days after exposure reduces lethality of severely irradiated mice

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