• Molecules and Cells
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• 제38권10호
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• pp.918-924
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• 2015

During T cell activation, mitochondrial content increases to meet the high energy demand of rapid cell proliferation. With this increase, the level of reactive oxygen species (ROS) also increases and causes the rapid apoptotic death of activated cells, thereby facilitating T cell homeostasis. Nicotinamide (NAM) has previously been shown to enhance mitochondria quality and extend the replicative life span of human fibroblasts. In this study, we examined the effect of NAM on $CD8^+$ T cell activation. NAM treatment attenuated the increase of mitochondrial content and ROS in T cells activated by CD3/CD28 antibodies. This was accompanied by an accelerated and higher-level clonal expansion resulting from attenuated apoptotic death but not increased division of the activated cells. Attenuation of ROS-triggered pro-apoptotic events and upregulation of Bcl-2 expression appeared to be involved. Although cells activated in the presence of NAM exhibited compromised cytokine gene expression, our results suggest a means to augment the size of T cell expansion during activation without consuming their limited replicative potential.

• Radiation Oncology Journal
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• 제9권1호
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• pp.7-15
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• 1991

Pentoxifylline (PENTO)는 적혈구의 유동성을 증가시켜 모세혈관의 적혈구 흐름을 증가시킨다. 또한 적혈구내 2,3-DPG를 증가시켜서 산소 친화력을 감소시켜 산소의 해리를 촉진시킨다. Nicotinamide (NA)는 종양내 혈류를 일시적으로 증가시켜서 종양내 급성 저산소 세포의 수를 감소시킨다. PENTO와 NA의 병용이 저산소 세포의 산소화에 의해서 방사선 감수성을 증가시킬 수 있는지를 확인하기 위하여 FSaII생쥐의 섬유육종을 이용하여 실험을 시행하였다. 방사선에 의한 성장 장애가 유의하게 증가하였으며, 증가율은 2.5~2.8이었다. $TCD_{50}$가 대조 종양군에서는 57Gy였으나 PENTO+NA투여 종양군에서는 32Gy로 1.8배의 $TCD_{50}$의 감소를 보였다. 정상피부의 방사선 감수성에는 영향이 없었다. PENTO+NA의 방사선 감수성의 증가를 규명하기 위하여 종양내 혈류의 변화, 종양내 산소농도를 laser Doppler flowmetry와 산소 미소전극 방법으로 측정하였다. PENTO+NA투여후 10분 경과하여 혈류가 유의하게 증가하였으며 종양내 산소 분압도 8 mmHg에서 19 mmHg로 유의하게 증가함을 관찰하였다. 따라서 PEHTO또는 NA단독보다 PENTO+NA병통이 더욱 효과적이라 사료되며 생체내 종양의 방사선 감수성의 증가는 종양내 산소의 증가로 생각되며 더욱 방사선 감수성을 증가시키기 위하여 여러 농도의 PENTO의 단독 또는 NA와의 병용등에 대한 지속적인 연구가 필요하다.

• Journal of Pharmaceutical Investigation
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• 제9권2호
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• pp.11-21
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• 1979

It has been reported from our department that a few agents, such as $K_2S_2O_5,\;NaHSO_3,$ nicotinamide have a marked stabilizing effect in vitro on metoclopramide which is relatively unstable compound. In order to study the effect of these stabilizers on the action of metoclopramide in vitro, the fate of this compound combined with $K_2S_2O_5,\;NaHSO_3$ and nicotinamide, respectively, was studied and furthermore, the change of the biological activity of metoclopramide due to these stabilizers was studied by using the isolated stomach strip of rat. The blood concentration of metoclopramide was measured by using Bakke's method at the various time after intravenous injection of the mixed metoclopramide solution with the stabilizers. In order to study the excretion of the drug, rabbits were anesthesized and catheterized into bladder for withdrawal of urine. After intravenous injection of the mixed metoclopramide solution, urine was collected for 5 hours and the conjugated forms of metoclopramide as well as the free form were determined by using Arita's method. In the biological study of the metoclopramide combined with stabilizers, the contractability of the isolated rat stomach strip was observed by using polygraph recorder. The results were following: 1. When metoclopramide was administered with nicotinamide as stabilizer, the blood concentration of the unchanged from and the rate of the clearance of this compound were very similar to that of metoclopramide alone. On the other hand, other stabilizers, $K_2S_2O_5\;and\;NaHSO_3$, brought about 40% decrease in blood concentration of the unchanged form at 15 min after intravenous injection however, the rate of clearance of metoclopramide with $K_2S_2O_5\;or\;NaHSO_3$ was very slow. 2. In the case of urinary excretion, the excretory pattern of the metabolites of metoclopramide with $NaHSO_3$ or nicotinamide was very similar to that of metoclopramide alone. But metodopramide plus $K_2S_2O_5$ group showed the maked depression of excretion for first 1 hour. 3. In composition of metabolites, when metoclopramide was administered with $K_2S_2O_5$ or $NaHSO_3$, the sulfonate conjugation was predominant. But the glucuronic acid conjugation was predominant in metoclopramide plus nicotinamide gronp. 4. In the experiments on the biological activity of the metoclopramide, this compound exhibited the marked contracting effect in isolatd rat stomach strip. Specially, the meetoclopramide combined with $K_2S_2O_5$ showed the strong contraction of the isolated strip, suggesting the potenciating effect of $K_2S_2O_5$ on the action of metoclopramide in the isolated strip.

• Natural Product Sciences
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• 제11권3호
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• pp.155-159
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• 2005

The aqueous extract of Coscinium fenestratum was studied for its antioxidant status in STZ-nicotinamide induced type 2 diabetic rats at two dose levels of 250 mg/kg and 500 mg/kg. At the end of the experimental period, diabetic rats treated with aqueous extract at both dose levels showed a significant increase in the levels of enzymatic antioxidants such as glutathione peroxidase, glutathione synthetase, peroxidase, superoxide dismutase and catalase as compared to the untreated control. Similarly, a significant increase was also observed in the levels of the non enzymatic antioxidants ceruloplasmin, ascorbic acid and tocopherol. The results suggest that the aqueous stem extract of C. fenestratum prevents type 2 diabetes mellitus induced oxidative stress.

• 미생물학회지
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• 제20권1호
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• pp.1-10
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• 1982

From Aspergillus nidulans, six suppressor mutants, MSI-MS6, were isolated, and their characteristics were analysed. These were the suppressor mutants for acriflavin resistant and nicotinamide auxotrophic mutant phenotypes. MS1, MS2, MS5 and MS6, were linked to the chromosome IV, I, II respectively, and MS2 was linked to one of the rest chromosomes, MS3 and MS6 mutants had both suppressors for acriflavin resistant marker and for nicotinamide auxotrophic marker. In order to know the stability and efficiency of the suppressors, their reversion frequencies, that is, frequencies of losing the suppressibility, were analysed. Only MS3 and MS5 were reversed with high frequency. The four mutants didn't lose their suppressibilities, and this meant that the suppressors of these four were very stable and highly effcient. The suppressor specificities of these mutants were tested for other mutant's phenotype marker. One of the six suppressors, MS1, had the suppressor specificity for acriflavin resistant marker of 163 strain.

• Archives of Pharmacal Research
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• 제28권6호
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• pp.637-647
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• 2005

This work includes the synthesis of 15 final compounds (6a-h and 7b-h) as prod rugs of 5-ASA in the form of the acid itself, esters and amides linked by an amide linkage through a spacer to the endocyclic ring N of nicotinamide. Also, 15 new intermediate compounds were prepared. The target compounds (6b, 6f, 7b, and 7e-h) revealed potent analgesic and anti-inflammatory activities in comparison to sulfasalazine and 5-ASA. In addition, ulcerogenicity, $LD_{50}$, in vivo and in vitro metabolism of compound 7f were determined.

• 미생물학회지
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• 제24권4호
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• pp.370-376
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• 1986

From the outer membrane portion of Gram-negative Klebsiella pneumoniae, the activity of 2-furaldehyde dehydrogenase depending upon beta-nicotinamide adenine dinucleotide was detected. Cytoplasmic membrane was preferentially extracted from crude membrane with $Mg^{2+}$ and Triton X-100, and then outer membrane was collected by ultracentrifugation. The crude enzyme was obtained by solubilization of outer membrane with lysozyme, ethylene diamine tetraacetate and Triton X-100. Thereafter 2-furaldehyde dehydrogenase was partially purified through column chromatography on QAE-Sephadex Q-50 and Sephadex G-150 and the enzyme activity was analyzed by means of high performance liquid chromatography. The optimal pH for the activity of the enzyme was about 9.5 and the optimal temperature was about $85^{\circ}C$. The partially purified enzyme retained tis activity at $85^{\circ}C$ for 5 hours. The optimal concentration of Triton X-100 for the activity of the enzyme was about 1.5% in the reaction mixture.

• BMB Reports
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• 제32권1호
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• pp.1-5
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• 1999

In order to understand the biological role of calmodulin in plants, transgenic tobacco plants expressing a calmodulin mutant (VU-4 calmodulin, lys to ile-115) gene have been analyzed. SDS-PAGE and Western-blot analyses showed that the foreign calmodulin mutant is stably and highly expressed in the transgenic tobacco plants. The levels of $H_2O_2$were elevated approximately 2-fold in the transgenic plants. Furthermore, the transgenic tobacco plants have more than 6-fold higher levels of NADPH compared to control tobacco plants. The present findings, combined with previous data showing differences in the susceptibility of the transgenic tobacco seeds and normal tobacco seeds to fungal contamination (Oh and Yang, 1996), suggest that the expression of the calmodulin derivative gene in tobacco plants could increase resistance to infection by fungal pathogens.

• 한국발생생물학회지:발생과생식
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• 제23권4호
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• pp.391-399
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• 2019

Nicotinamide is used to maturate pancreatic progenitors from embryonic stem cells (ESCs) into insulin-producing cells (IPCs). It has been known that nicotinamide inhibits the enzymatic activity of SIRT1, an NAD⁺-dependent deacetylase. Here we show that SIRT1 knockdown enhances the differentiation of human ESCs into IPCs. SIRT1 knockdown enhances the clustering size of IPCs and the expression of pancreatic genes including c-peptide, pancreas/duodenum homeobox protein 1 (PDX1), insulin, somatostatin, glucagon and Nkx6.1 in human ESC-derived IPCs. In addition, We found that IPCs differentiated from SIRT1 knockdowned human ESCs have more zinc compared to those from control human ESCs. Our data suggest that SIRT1 negatively regulates the differentiation of β cells from human ESCs.

• Journal of Microbiology
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• 제33권3호
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• pp.234-238
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• 1995

The breakdown rate of NAD in Salmonella typhimurium was investigated both in aerobic and anaerobic conditions. After NAD is broken down to nicotinamide ring containing moiety, almost all the nicotinamide ring containing moiety recycles back to NAD pool. However almost none of the adenine containing moiety recycles back. We pulse-label the endogeneous NAD with [$\^$14/C]-adenine and [$\^$3/H]- niacin. The remaining [$\^$14/C]-radioactivity in NAD pool at each time was regarded as unbroken portion of NAD, WHERE AS THE OF [$\^$3/H] was served as a total amount of NAD to start with. Under aerobic condition, the half-life of NAD was around 2 hours. However, the breakdown rate was significantly reduced (around 3-5 fold) under anaerobic condition. The observation that under aerobic conditions, NAD turnover is considerably faster than under anaerobic conditions suggests that oxygen has important effect in NAD breakdown.