• Title/Summary/Keyword: Nicotinamide

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SIRT7 Exhibits Oncogenic Potential in Human Ovarian Cancer Cells

  • Wang, Hong-Ling;Lu, Ren-Quan;Xie, Su-Hong;Zheng, Hui;Wen, Xue-Mei;Gao, Xiang;Guo, Lin
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3573-3577
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    • 2015
  • Background: Sirtuin7 (SIRT7) is a type of nicotinamide adenine dinucleotide oxidized form (NAD+)-dependent deacetylase and the least understood member of the sirtuins family; it is implicated in various processes, such as aging, DNA damage repair and cell signaling transduction. There is some evidence that SIRT7 may function as a tumor trigger for human malignancy. Here, we aimed to explore the biological function of SIRT7 in ovarian carcinoma cells and its potential mechanism. Materials and Methods: Expression of SIRT7 in ovarian cancer cell lines was detected by western blotting. Transduced cell lines with SIRT7 knockdown or overexpression were constructed. Cell viability, cologenic, apoptosis-associated and motility assays were performed to elucidate the biological function of SIRT7 in ovarian cancer cells. Results: SIRT7 demonstrated a higher level in ovarian cancer cell lines compared with normal cells. On the one hand, down-regulation of SIRT7 significantly reduced ovarian cancer cell growth, repressed colony formation and increased cancer cell apoptosis; on the other hand, up-regulation promoted the migration of cancer cells. Additionally, repression of SIRT7 also induced change in apoptosis-related molecules and subunits of the NF-${\kappa}B$ family. Conclusions: In the present study, our data indicated that SIRT7 might play a role of oncogene in ovarian malignancy and be a potential therapeutic target.

Protective Mechanism of Hominis Placenta Extract Against ${H_2O_2}-Induced$ Apoptosis in $PGT-{\beta}$ Cells ($PGT-{\beta}$ 세포주에서 자하거 약침액의 $H_2O_2$로 인한 Apoptosis에 대한 방어 기전)

  • Jung-Chul, Seo;Jae-Dong, Lee;Dong-Suk, Park;Sung-Keel, Kang;Byung-Cheol, Ahn;Ee-Hwa, Kim;Soon-Ae, Kim;Hee-Jae, LeeK;Chang-Ju, Kim
    • The Journal of Korean Medicine
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    • v.22 no.3
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    • pp.92-97
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    • 2001
  • 목적 :본 연구는 최근 임상에서 많이 사용하는 자하거 약침액이 과산화수소($H_2O_2$)로 야기된 송과선 세포의 Apoptosis에 있어서 세포 보호에 미치는 영향과 그 기전을 분석하였다. 방법 :송과선 세포주에서 자하거 약침액의 $H_2O_2$로 인한 Apoptosis에 대한 방어 기전을 관찰하기 위하여 면역세포화학법. 세포화학법 및 reverse transcription-polymerase chain reaction (RT-PCR)을 시행하였다. 결과 : 자하거 약침액 투여군에서는 nuclear factor kappa B (NFkB), inducible nitric oxide synthase (iNOS), nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase의 발현이 $H_2O_2$ 투여군보다 감소하였다. RT-PCR에서는 caspase-3의 발현이 자하거 약침액 투여군에서 $H_2O_2$ 투여군보다 억제되었다. 결론: 이상의 결과를 통하여 자하거 약침액이 $H_2O_2$로 유발된 Apoptosis에서 세포보호 효과가 있으며 그 기전은 iNOS와 caspase-3의 억제에 기인할 가능성을 시사한다고 하겠다.

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Exposure Assessment of Vitamins and Minerals from Various Sources of Koreans (다양한 급원을 통한 우리나라 사람들의 비타민 및 무기질 노출량 평가)

  • Kim, Sun-Hyo;Lee, Seon-Huei;Hwang, Yu-Jin;Kim, Wha-Young
    • Journal of Nutrition and Health
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    • v.39 no.6
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    • pp.539-548
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    • 2006
  • In recent years a concern of excessive intakes of vitamins and minerals from various sources is increasing, since there has been a marked increase in production and consumption of vitamin and mineral supplements and fortified foods. The purpose of this study was to assess the maximum exposure of vitamins and minerals from various sources including diet, fortified foods, and health functional foods among Koreans. As a result, the highest exposure group of most vitamins and minerals from diet was adults (30 - 49 years of age) according to 2001 Korean National Nutrition and Health Survey Report. Maximum dietary intakes of vitamin A, $B_1,\;B_2$, C, nicotinamide, calcium, phosphorus and iron were 0.5 - 7 times of the RDA for Koreans, 7th ed. Maximum intakes of vitamins and minerals from fortified foods by adults (20 - 59 years of age) were 8 - 760% of the Korean RDA. In addition, maximum exposure of vitamins and minerals from vitamin mineral health functional foods by middle aged people was 35 - 140% of the upper limits (UL: DRI for Koreans). As a consequence, maximum combined intakes of vitamin $B_6$, vitamin C, calcium, iron and zinc from the above sources including diet, fortified foods and vitamin mineral health functional foods were greater than the UL. These results would be applied for determining the safe upper limits of vitamin and mineral of health functional foods.

Assessing the Systemic Toxicity in Rabbits after Sub Acute Exposure to Ocular Irritant Chemicals

  • Reshma, Cherian Sebastian;Sruthi, Sudhakaran;Syama, Santhakumar;Gayathri, Vishwanath;Mohanan, Parayanthala Valappil
    • Toxicological Research
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    • v.31 no.1
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    • pp.49-59
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    • 2015
  • Eye is a highly vascularised organ. There are chances that a foreign substance can enter the systemic circulation through the eye and cause oxidative stress and evoke immune response. Here the eyes of rabbits were exposed, for a period of 7 days, to 5 known ocular irritants: Cetyl pyridinium chloride (CPC), sodium salicylate (SS), imidazole (IMI), acetaminophen (ACT) and nicotinamide (NIC). The eyes were scored according to the draize scoring. Blood collected from the treated rabbit were analyzed for haematological and biochemical parameters. After sacrifice, histological analysis of the eye and analysis of pro-inflammatory biomarkers ($IL-1{\alpha}$, $IL-1{\beta}$, IL-8 and $TNF-{\alpha}$) in the cornea using ELISA was carried out. Spleen was collected and the proliferation capacities of spleenocytes were analyzed. Liver and brain were collected and assessed for oxidative stress. The eye irritation potential of the chemicals was evident from the redness and swelling of the conjunctiva and cornea. Histopathological analysis and ELISA assay showed signs of inflammation in the eye. However, the haematological and biochemical parameters showed no change. Spleenocyte proliferations showed only slight alterations which were not significant. Also oxidative stress in the brain and liver were negligible. In conclusion, chemicals which cause ocular irritation and inflammation did not show any systemic side-effects in the present scenario.

Hypocholesterolemic Soybean Peptide (IAVP) Inhibits HMG-CoA Reductase in a Competitive Manner

  • Pak, Valeriy V.;Koo, Min-Seon;Lee, Na-Ri;Oh, Su-Kyung;Kim, Myung-Sunny;Lee, Jong-Soo;Kwon, Dae-Young
    • Food Science and Biotechnology
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    • v.14 no.6
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    • pp.727-731
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    • 2005
  • Synthesized Ile-Ala-Val-Pro (IAVP) peptide, which has the highest hypocholesterolemic effect among a number of synthesized derivatives of Ile-Ala-Val-Pro-Gly-Glu-Val-Ala (IAVPGEVA) isolated from 11S globulin of soy protein by pepsin digestion, was selected for investigation in the present study. Using a recombinant Syrian hamster 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), we studied in detail the inhibition of this enzyme by IAVP and compared the action of this peptide to that of lovastatin, a known competitive inhibitor of this enzyme. The concentration of IAVP required for 50% inhibition ($IC_{50}$) of HMGR activity in given experimental conditions was $340\;{\mu}M$. Kinetic analysis revealed that the studied peptide is a competitive inhibitor of HMGR with respect to both 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) and nicotinamide adenine dinucleotide phosphate (NADPH), with an equilibrium constant of inhibitor binding ($K_i\;=\;[E][I]/[EI]$) of $61{\pm}1.2\;{\mu}M$ and $157{\pm}4.4\;{\mu}M$, respectively. At the same conditions, $K_i$ and $IC_{50}$ for lovastatin were $2.2{\pm}0.1\;nM$ and 12.5 nM, respectively. Thus, the given peptide interacts with HMGR as a bisubstrate, consequently blocking access of both substrates to the active sites. The achieved results suggest the design of new peptide sequences having a higher relative affinity to binding sites of this enzyme and an enhancement of their hypocholesterolemic properties.

Enhanced Production of hCTLA4Ig by Suppressing Cell Death in Transgenic Rice Cell Suspension Cultures (형질전환 벼 현탁세포 배양에서 세포 사멸 억제를 통한 hCTLA4Ig 생산성 증대)

  • Kim, Myong-Sik;Nam, Hyung-Jin;Kim, Min-Sub;Kwon, Jun-Young;Kim, Dong-Il
    • KSBB Journal
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    • v.28 no.4
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    • pp.260-268
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    • 2013
  • Transgenic plant cell cultures are an attractive expression system for the production of industrial and pharmaceutical proteins because of their advantages in safety and low production cost. Human cytotoxic T-lymphocyte antigen 4-immunoglobulin (hCTLA4Ig) was produced and secreted when sugar was depleted in culture medium by transgenic rice cell lines (Oryza sativa L.) using RAmy3D promoter. Due to the production of the target protein by sugar depletion, concomitant occurrence of cell death is inevitable. For that reason, inhibition of cell death for enhancing productivity was necessary for the production period without energy sources. Supplementation of 0.1 mM sodium nitroprusside improved cell viability by 1.4-fold and maximum hCTLA4Ig production by 1.3-fold compared to those of control. Addition of 1 and 10 mM glutathione, N-acetylcysteine (NAC), and nicotinamide inhibited apoptotic-like programmed cell death by decreasing the activity of reactive oxygen species. Production hCTLA4Ig was enhanced 1.4-, 1.25-, and 1.15-fold with 10 mM NAC, 1 mM NAC, and 1 mM glutathione, respectively. In addition, it was found that the supplementation of NAC enhanced the cell viability.

Effects of Aconitum pseudo-laeve on Nitric Oxide Synthase in the Periaqueductal Gray of Collagenase-induced Rat Osteoarthritis Model (진범 약침이 collagenase로 유도된 흰쥐 골관절염 모델에서 NOS 발현에 미치는 영향)

  • Kim, Hyun-Soo;Seo, Il-Bok;Park, Se-Keun;Kim, Jeong-Seon;Seo, Jung-Chul;Choi, Sun-Mi;Koo, Sung-Tae;Kim, Ee-Hwa
    • Korean Journal of Acupuncture
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    • v.23 no.1
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    • pp.87-94
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    • 2006
  • 목적 :본 연구는 collagenase로 유도된 흰쥐의 골관절염 모델에서 진범약침자극이 흰쥐 dorsolateral periaqueductal gray (DL-PAG)에서 NOS 및 nNOS 발현에 미치는 영향을 관찰하였다. 방법 : 흰쥐의 관절강내로 collagenase 용액을 주사하여 골관절염 모델을 만들고 정상군, 대조군 및 진범약침군으로 실험군을 분류한 후, nNOS(neuronal NOS)와 NOS에 대하여 미치는 영향을 nNOS immunohistochemistry와 nicotinamide adenine dinucleotide phosphate-diaphorase(NADPH-d) 검사법을 통하여 조사하였다. 결과 : 골관절염이 유발된 흰쥐의 DL-PAG 영역에서 nNOS와 NOS의 발현억제가 관찰되었으며, 진범약침군이 collagenase로 유도된 골관절염에서 감소된 nNOS와 NOS의 발현이 증가되었다. 결론 : 본 연구를 통하여 진범약침자극은 골관절염이 유발된 흰쥐의 DL-PAG에서의 nNOS와 NOS의발현에 영향을 미친다는 결과를 얻을 수 있었다.

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Effects of Clematis mandshurica Rupr. on Nitric Oxide Synthase in the Periaqueductal Gray of Collagenase-induced Rat Osteoarthritis Model (위령선 약침이 콜라겐으로 유도된 골관절염 모델에서 흰쥐의 PAG 영역에서 NOS 발현에 미치는 영향)

  • Yang, Kook-Jung;Kim, Soon-Joong;Seo, Il-Bok;Park, Se-Keun;Kim, Jeong-Seon;Seo, Jung-Chul;Choi, Sun-Mi;Lee, Hye-Jung;Kim, Ee-Hwa
    • Korean Journal of Acupuncture
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    • v.22 no.4
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    • pp.109-116
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    • 2005
  • 목적 : 골관절염은 진통을 수반하는 퇴행성 관절질환이며, 장애를 일으키는 주요한 원인이 된다. 또한 노인들에 있어서 골관절염은 매우 흔한 질환이라 할 수 있다. Nitric oxide(NO)는 Nitric Oxide Synthase(NOS)에 의하여 칼슘의존성통로를 통하여 L-arginine 으로부터 합성되어지며, NO는 중추신경계에 있어서 중요한 세포사이의 전달자이다. 방법 :본 연구에서는 위령선 으로부터 추출한 액이 콜라겐으로 유도된 관절염에 걸린 쥐의 dorsolateral periaqueductal gray(DL-PAG) 영역에서 nNOS(neuronal NOS)와 NOS에 대하여 미치는 영향 을 nNOS immunohistochemistry와 nicotinamide adenine dinucleotide phosphate-diaphorase(NADPH-d) 검사법을 통하여 조사하였다. 결과 : 골관절염이 유발된 흰쥐의 DL-PAG 영역에서 nNOS와 NOS의 발현억제가 관찰되었으며, 위령선이 콜라겐으로 유도된 골관절염에서 감소된 nNOS와 NOS의 발현이 증가되었다. 결론 : 본 연구를 통하여 위령선은 골관절염이 유발된 흰쥐의 DL-PAG에서의 nNOS와 NOS의 발현에 영향을 미친다는 결과를 얻을 수 있었다.

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The Effects of Lycii Radicis Cortex on Inflammatory Response through an Oxidative Stress and AGEs-mediated Pathway in STZ-induced Diabetic Rats

  • Jung, Yu Sun;Shin, Hyeon Cheol
    • The Journal of Korean Medicine
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    • v.37 no.2
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    • pp.62-75
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    • 2016
  • Objectives: This study examined whether Lycii Radicis Cortex has an inhibitory effect on inflammatory response through an oxidative stress and advanced glycation endproducts (AGEs)-mediated pathway in streptozotocin (STZ)-induced type 1 diabetic rats. Methods: Lycii Radicis Cortex was orally administered to STZ-induced diabetic rats in doses of 80 or 160 mg/kg body weight/day for 2 weeks, and its effects were compared with those of diabetic control and normal rats. Results: The administration of Lycii Radicis Cortex decreased the elevated serum urea nitrogen and renal reactive oxygen species (ROS), and reduced the increased AGEs in the serum and kidney. The elevated protein expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits in the kidney of diabetic control rats were significantly decreased after Lycii Radicis Cortex treatments. Moreover, the kidney of diabetic rats exhibited the up-regulation of receptor for AGEs (RAGE) and AGEs-related proteins; however, Lycii Radicis Cortex treatment also significantly reduced those expressions (excepted RAGE). In addition, the diabetic rats exhibited an up-regulation of the expression of proteins related to inflammation in the kidney, but Lycii Radicis Cortex administration reduced significantly the expression of the inflammatory proteins through the nuclear factor-kappa B (NF-${\kappa}B$) and activator protein-1 (AP-1) pathways. Conclusions: This study provides scientific evidence that Lycii Radicis Cortex exerts the antidiabetic effect by inhibiting the expressions of AGEs and NF-${\kappa}B$ in the STZ-induced diabetic rats.

Trichostatin A Modulates Angiotensin II-induced Vasoconstriction and Blood Pressure Via Inhibition of p66shc Activation

  • Kang, Gun;Lee, Yu Ran;Joo, Hee Kyoung;Park, Myoung Soo;Kim, Cuk-Seong;Choi, Sunga;Jeon, ByeongHwa
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.5
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    • pp.467-472
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    • 2015
  • Histone deacetylase (HDAC) has been recognized as a potentially useful therapeutic target for cardiovascular disorders. However, the effect of the HDAC inhibitor, trichostatin A (TSA), on vasoreactivity and hypertension remains unknown. We performed aortic coarctation at the inter-renal level in rats in order to create a hypertensive rat model. Hypertension induced by abdominal aortic coarctation was significantly suppressed by chronic treatment with TSA (0.5 mg/kg/day for 7 days). Nicotinamide adenine dinucleotide phosphate-driven reactive oxygen species production was also reduced in the aortas of TSA-treated aortic coarctation rats. The vasoconstriction induced by angiotensin II (Ang II, 100 nM) was inhibited by TSA in both endothelium-intact and endothelium-denuded rat aortas, suggesting that TSA has mainly acted in vascular smooth muscle cells (VSMCs). In cultured rat aortic VSMCs, Ang II increased p66shc phosphorylation, which was inhibited by the Ang II receptor type I ($AT_1R$) inhibitor, valsartan ($10{\mu}M$), but not by the $AT_2R$ inhibitor, PD123319. TSA ($1{\sim}10{\mu}M$) inhibited Ang II-induced p66shc phosphorylation in VSMCs and in HEK293T cells expressing $AT_1R$. Taken together, these results suggest that TSA treatment inhibited vasoconstriction and hypertension via inhibition of Ang II-induced phosphorylation of p66shc through $AT_1R$.