NaNO_2预处理对过氧化损伤PC12细胞的保护作用
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摘要
目的:探讨低剂量亚硝酸钠(NaNO_2)预处理对过氧化损伤鼠肾上腺嗜铬细胞瘤(PC12)细胞的保护作用;同时观察其诱导PC12细胞分化的作用。
方法:分别以系列浓度的NaNO_2作用PC12细胞不同时间,采用四甲基偶氮唑蓝(MTT)法检测NaNO_2对PC12细胞活力的影响,研究剂量-效应和时间-效应关系,寻找最低促增殖效应剂量和最佳促增殖效应时间。过氧化损伤PC12细胞模型制作采用400 mmol·L~(-1)乙醇、45 mmol·L~(-1) NaNO_2、1.1 mmol·L~(-1)过氧化氢(H_2O_2)处理2 h。细胞增殖指标采用MTT、活细胞计数法、Hoechst33258荧光单染计数有丝分裂指数;细胞凋亡检测采用Hoechst33258染色计数细胞凋亡率、流式细胞术(FITC-annexinⅤ/ PI)双染法和Hoechst 33258/PI活细胞染色法;比色法测定超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活力和谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)含量。Western-blotting检测相关蛋白表达。瑞氏染色观察PC12细胞分化状态。
结果:MTT结果显示,低剂量NaNO_2促进细胞增殖,高剂量抑制其增殖,剂量-效应关系呈典型的倒U型曲线。NaNO_2最低促增殖剂量为(促增殖效应高于对照组的15%)0.14 mmol·L~(-1),最佳促增殖效应时间点出现在第24 h;400 mmol·L~(-1)乙醇、45 mmol·L~(-1)的NaNO_2、1.1 mmol·L~(-1) H_2O_2作用PC12细胞2 h,流式细胞术结果显示,细胞凋亡率分别为(50.63±2.14)%、(52.06±8.32)%、(53.6±8.51)%,用0.14 mmol·L~(-1) NaNO_2预处理细胞24 h,再分别用上述氧化剂作用2 h,细胞凋亡率分别下降为(19.71±3.19)%、(19.65±2.17)%、(18.23±4.19)%差异具有显著性(P﹤0.05);用0.14 mmol·L~(-1) NaNO_2和一氧化氮清除剂(c-PTIO)预处理细胞24 h,再用上述氧化剂作用2 h,细胞凋亡率则分别为(32.28±7.31)%、(38.63±5.08)%、(30.75±3.81)%。Hoechst 33258染色、Hoechst 33258/PI活细胞染色计数细胞死亡率结果与其相似。
用400 mmol·L~(-1)乙醇作用PC12细胞2 h,SOD、CAT酶活性,GSH-Px、MDA含量分别为(20.95±1.68) U/mg. Prot、(11.45±0.93) U/mg. Prot、(41.17±2.72)μmol/mg. Prot、(98.38±11.5)μmol/mg .Prot,用NaNO_2预处理细胞再用乙醇作用,SOD、CAT酶活性和GSH-Px、MDA含量分别为(62.38±2.98)U/mg. Prot、(19.29±0.27) U/mg. Prot、(62.59±1.41)μmol/mg.Prot、(49.38±2.93)μmol/mg.Prot;用NaNO_2+c-PTIO预处理细胞24 h,再用乙醇作用2 h,SOD、CAT酶活性和GSH-Px、MDA含量分别为(40.23±1.57)U/mg.Prot、(15.98±1.9) U/mg.Prot、(51.21±1.52)μmol/mg.Prot、(73.58±14.7)μmol/mg.Prot。用NaNO_2预处理再用乙醇作用组,与单纯乙醇组相比,Bax、Caspase-9、Caspase-3蛋白表达量降低,Bcl-2和HIF~(-1)α蛋白表达量升高(P﹤0.05);c-PTIO可以部分逆转这种现象。45 mmol·L~(-1) NaNO_2和1.1 mmol·L~(-1) H_2O_2处理细胞,上述各指标变化情况与乙醇组一致。瑞氏染色结果显示,0.14 mmol·L~(-1) NaNO_2作用PC12细胞48 h,明显促进PC12细胞突起生长,缺氧诱导因子(HIF~(-1)α)、血管内皮生长因子(VEGF)表达量增加,作用效果类似神经生长因子(NGF)。c-PTIO可以部分抑制这种现象。
结论:
1.低剂量NaNO_2促进PC12细胞增殖,高剂量抑制其增殖,剂量-效应关系呈典型的倒U型曲线。
2.低剂量NaNO_2预处理能够使PC12细胞抗氧化酶活性增强、脂质过氧化水平降低、HIF~(-1)α的表达增加,对过氧化损伤的细胞有保护作用。
3.低剂量NaNO_2可以促进PC12细胞分化。
Objective: To study the cytoprotective role of Low-dose sodium nitrite preconditioning against the peroxide-induced damage and to observe the differentiation of sodium nitrite in PC12 cells.
Methods: PC12 cells were treated with different concentrations of sodium nitrite for different times, the cell viability was measured by MTT to find the minimum sodium nitrite dose and the optimum time which could promote the cell proliferation . The PC12 cells were treated with 400 mmol·L~(-1) ethanol, 45 mmol·L~(-1) NaNO_2 and 1.1 mmol·L~(-1)H_2O_2 for 2h to establish the peroxide-induced damaged cell model.The proliferation of PC12 cell was detected by MTT, cell counting and Hochest33258 staining. FITC-annexinⅤ/PI flow cytometry , Hoechst33258 staining and Hoechst 33258/PI staining were used to detect the cells apoptosis. Colorimetric technique was performed to measure the SOD, CAT and GSH-Px , MDA. Western-blotting to detect the expression of the apoptosis-related protein. Wright's staining to observe the differentiation of PC12 cell.
Results: Dose-responses results showed that NaNO_2 on PC12 cells proliferation was typical inverted U-shaped curve.The concentration of the minimum stimulatory response was 0.14 mmol·L~(-1)(more than 15% of the control group)and the maximum stimulatory response at the 24 h. The PC12 cells were treated with 400 mmol·L~(-1) ethanol, 45 mmol·L~(-1) NaNO_2 and 1.1 mmol·L~(-1) H_2O_2 for 2 h, Flow cytometry assay show the apoptosis rate of the cells were (50.63±2.14)%, (52.06±8.32)%, (53.6±8.51)% respectively. The PC12 cells were pretreated with 0.14 mmol·L~(-1) NaNO_2 for 24 h then treated with the oxygenants above-metioned for 2 h, the apoptosis rate of the cells were decreased as (19.71±3.19)%, (19.65±2.17)%, (18.23±4.19)% respectively(P﹤0.05). While NaNO_2 and nitric oxide specific scavenger c-PTIO combined to treat the cells for 24 h, then treated with the oxygenants above-metioned for 2 h, the apoptosis rate of the cells were (32.28±7.31)%, (38.63±5.08)%, (30.75±3.81)% respectively. The results of Hoechst33258 staining, Hoechst 33258/PI staining and cell counting are same as flow cytometry. The PC12 cells were treated with 400 mmol·L~(-1) ethanol, the activities of SOD, CAT, GSH-Px and the levels of MDA were (20.95±1.68)U/mg.Prot, (11.45±0.93) U/mg.Prot, (41.17±2.72)μmol/mg.Prot, (98.38±11.5)μmol/mg.Prot respectively. The PC12 cells were pretreated with NaNO_2 then treated with ethanol, the activities of SOD, CAT and the levels of GSH-Px, MDA were (92.38±2.98) U/mg. Prot, (19.29±0.27 ) U/mg.Prot, (62.59±1.41)μmol/mg.Prot, (49.38±2.93)μmol/mg.Prot. While NaNO_2 and nitric oxide specific scavenger c-PTIO combined to treat the cells for 24 h, then treated with the oxygenants above-metioned for 2 h, the activities of SOD, CAT and the levels of GSH-Px, MDA were (50.23±1.57) U/mg.Prot, (15.98±1.9) U/mg.Prot, (51.21±1.52)μmol/mg.Prot, (73.58±14.7)μmol/mg.Prot. Western blotting showed that in ethanol treated cells pretreated with NaNO_2, the expression of Bax, Caspase-9, Caspase-3 were decreased, HIF-1αand Bcl-2 were increased(P﹤0.05). Add to c-PTIO could reverse this phenomenon. The results of 45 mmol·L~(-1) NaNO_2 and1.1 mmol·L~(-1) H_2O_2 were same as ethanol group. The PC12 cells were treated with 0.14 mmol·L~(-1) NaNO_2 for 48h, the results of wright's staining showed that NaNO_2 have the same effects of NGF, including prolong the prominency of the cells, and increase the expressions of HIF-1 and VEGF .
Conclusions:
1. Dose-responses results showed that NaNO_2 on PC12 cells proliferation was typical inverted U-shaped curve.
2. The PC12 cells were pretreated with low dose of NaNO_2 could increase their anti-oxidant activities and expressions of HIF-1α, resist the apoptosis induced by ethanol, high dose of NaNO_2 and H_2O_2. The mechanism might be related with the reduction of NaNO_2 to NO and the increased expressions of HIF-1α.
3. NaNO_2 could promote the differentiation of PC12 cells.
方法:分别以系列浓度的NaNO_2作用PC12细胞不同时间,采用四甲基偶氮唑蓝(MTT)法检测NaNO_2对PC12细胞活力的影响,研究剂量-效应和时间-效应关系,寻找最低促增殖效应剂量和最佳促增殖效应时间。过氧化损伤PC12细胞模型制作采用400 mmol·L~(-1)乙醇、45 mmol·L~(-1) NaNO_2、1.1 mmol·L~(-1)过氧化氢(H_2O_2)处理2 h。细胞增殖指标采用MTT、活细胞计数法、Hoechst33258荧光单染计数有丝分裂指数;细胞凋亡检测采用Hoechst33258染色计数细胞凋亡率、流式细胞术(FITC-annexinⅤ/ PI)双染法和Hoechst 33258/PI活细胞染色法;比色法测定超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活力和谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)含量。Western-blotting检测相关蛋白表达。瑞氏染色观察PC12细胞分化状态。
结果:MTT结果显示,低剂量NaNO_2促进细胞增殖,高剂量抑制其增殖,剂量-效应关系呈典型的倒U型曲线。NaNO_2最低促增殖剂量为(促增殖效应高于对照组的15%)0.14 mmol·L~(-1),最佳促增殖效应时间点出现在第24 h;400 mmol·L~(-1)乙醇、45 mmol·L~(-1)的NaNO_2、1.1 mmol·L~(-1) H_2O_2作用PC12细胞2 h,流式细胞术结果显示,细胞凋亡率分别为(50.63±2.14)%、(52.06±8.32)%、(53.6±8.51)%,用0.14 mmol·L~(-1) NaNO_2预处理细胞24 h,再分别用上述氧化剂作用2 h,细胞凋亡率分别下降为(19.71±3.19)%、(19.65±2.17)%、(18.23±4.19)%差异具有显著性(P﹤0.05);用0.14 mmol·L~(-1) NaNO_2和一氧化氮清除剂(c-PTIO)预处理细胞24 h,再用上述氧化剂作用2 h,细胞凋亡率则分别为(32.28±7.31)%、(38.63±5.08)%、(30.75±3.81)%。Hoechst 33258染色、Hoechst 33258/PI活细胞染色计数细胞死亡率结果与其相似。
用400 mmol·L~(-1)乙醇作用PC12细胞2 h,SOD、CAT酶活性,GSH-Px、MDA含量分别为(20.95±1.68) U/mg. Prot、(11.45±0.93) U/mg. Prot、(41.17±2.72)μmol/mg. Prot、(98.38±11.5)μmol/mg .Prot,用NaNO_2预处理细胞再用乙醇作用,SOD、CAT酶活性和GSH-Px、MDA含量分别为(62.38±2.98)U/mg. Prot、(19.29±0.27) U/mg. Prot、(62.59±1.41)μmol/mg.Prot、(49.38±2.93)μmol/mg.Prot;用NaNO_2+c-PTIO预处理细胞24 h,再用乙醇作用2 h,SOD、CAT酶活性和GSH-Px、MDA含量分别为(40.23±1.57)U/mg.Prot、(15.98±1.9) U/mg.Prot、(51.21±1.52)μmol/mg.Prot、(73.58±14.7)μmol/mg.Prot。用NaNO_2预处理再用乙醇作用组,与单纯乙醇组相比,Bax、Caspase-9、Caspase-3蛋白表达量降低,Bcl-2和HIF~(-1)α蛋白表达量升高(P﹤0.05);c-PTIO可以部分逆转这种现象。45 mmol·L~(-1) NaNO_2和1.1 mmol·L~(-1) H_2O_2处理细胞,上述各指标变化情况与乙醇组一致。瑞氏染色结果显示,0.14 mmol·L~(-1) NaNO_2作用PC12细胞48 h,明显促进PC12细胞突起生长,缺氧诱导因子(HIF~(-1)α)、血管内皮生长因子(VEGF)表达量增加,作用效果类似神经生长因子(NGF)。c-PTIO可以部分抑制这种现象。
结论:
1.低剂量NaNO_2促进PC12细胞增殖,高剂量抑制其增殖,剂量-效应关系呈典型的倒U型曲线。
2.低剂量NaNO_2预处理能够使PC12细胞抗氧化酶活性增强、脂质过氧化水平降低、HIF~(-1)α的表达增加,对过氧化损伤的细胞有保护作用。
3.低剂量NaNO_2可以促进PC12细胞分化。
Objective: To study the cytoprotective role of Low-dose sodium nitrite preconditioning against the peroxide-induced damage and to observe the differentiation of sodium nitrite in PC12 cells.
Methods: PC12 cells were treated with different concentrations of sodium nitrite for different times, the cell viability was measured by MTT to find the minimum sodium nitrite dose and the optimum time which could promote the cell proliferation . The PC12 cells were treated with 400 mmol·L~(-1) ethanol, 45 mmol·L~(-1) NaNO_2 and 1.1 mmol·L~(-1)H_2O_2 for 2h to establish the peroxide-induced damaged cell model.The proliferation of PC12 cell was detected by MTT, cell counting and Hochest33258 staining. FITC-annexinⅤ/PI flow cytometry , Hoechst33258 staining and Hoechst 33258/PI staining were used to detect the cells apoptosis. Colorimetric technique was performed to measure the SOD, CAT and GSH-Px , MDA. Western-blotting to detect the expression of the apoptosis-related protein. Wright's staining to observe the differentiation of PC12 cell.
Results: Dose-responses results showed that NaNO_2 on PC12 cells proliferation was typical inverted U-shaped curve.The concentration of the minimum stimulatory response was 0.14 mmol·L~(-1)(more than 15% of the control group)and the maximum stimulatory response at the 24 h. The PC12 cells were treated with 400 mmol·L~(-1) ethanol, 45 mmol·L~(-1) NaNO_2 and 1.1 mmol·L~(-1) H_2O_2 for 2 h, Flow cytometry assay show the apoptosis rate of the cells were (50.63±2.14)%, (52.06±8.32)%, (53.6±8.51)% respectively. The PC12 cells were pretreated with 0.14 mmol·L~(-1) NaNO_2 for 24 h then treated with the oxygenants above-metioned for 2 h, the apoptosis rate of the cells were decreased as (19.71±3.19)%, (19.65±2.17)%, (18.23±4.19)% respectively(P﹤0.05). While NaNO_2 and nitric oxide specific scavenger c-PTIO combined to treat the cells for 24 h, then treated with the oxygenants above-metioned for 2 h, the apoptosis rate of the cells were (32.28±7.31)%, (38.63±5.08)%, (30.75±3.81)% respectively. The results of Hoechst33258 staining, Hoechst 33258/PI staining and cell counting are same as flow cytometry. The PC12 cells were treated with 400 mmol·L~(-1) ethanol, the activities of SOD, CAT, GSH-Px and the levels of MDA were (20.95±1.68)U/mg.Prot, (11.45±0.93) U/mg.Prot, (41.17±2.72)μmol/mg.Prot, (98.38±11.5)μmol/mg.Prot respectively. The PC12 cells were pretreated with NaNO_2 then treated with ethanol, the activities of SOD, CAT and the levels of GSH-Px, MDA were (92.38±2.98) U/mg. Prot, (19.29±0.27 ) U/mg.Prot, (62.59±1.41)μmol/mg.Prot, (49.38±2.93)μmol/mg.Prot. While NaNO_2 and nitric oxide specific scavenger c-PTIO combined to treat the cells for 24 h, then treated with the oxygenants above-metioned for 2 h, the activities of SOD, CAT and the levels of GSH-Px, MDA were (50.23±1.57) U/mg.Prot, (15.98±1.9) U/mg.Prot, (51.21±1.52)μmol/mg.Prot, (73.58±14.7)μmol/mg.Prot. Western blotting showed that in ethanol treated cells pretreated with NaNO_2, the expression of Bax, Caspase-9, Caspase-3 were decreased, HIF-1αand Bcl-2 were increased(P﹤0.05). Add to c-PTIO could reverse this phenomenon. The results of 45 mmol·L~(-1) NaNO_2 and1.1 mmol·L~(-1) H_2O_2 were same as ethanol group. The PC12 cells were treated with 0.14 mmol·L~(-1) NaNO_2 for 48h, the results of wright's staining showed that NaNO_2 have the same effects of NGF, including prolong the prominency of the cells, and increase the expressions of HIF-1 and VEGF .
Conclusions:
1. Dose-responses results showed that NaNO_2 on PC12 cells proliferation was typical inverted U-shaped curve.
2. The PC12 cells were pretreated with low dose of NaNO_2 could increase their anti-oxidant activities and expressions of HIF-1α, resist the apoptosis induced by ethanol, high dose of NaNO_2 and H_2O_2. The mechanism might be related with the reduction of NaNO_2 to NO and the increased expressions of HIF-1α.
3. NaNO_2 could promote the differentiation of PC12 cells.
引文
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[33] Sun D, Liu CX, Ma YY, et al . Protective effect of prostaglandin e1 on renal microvascular injury in rats of acute aristolochic Acid nephropathy[J]. Ren Fail, 2011, 33(2): 225- 232.
[34] Cheng W, Zhou W. Clinical significance and relationship between HIF-1alpha, COX-2, VEGF and microvessel density expression in laryngeal carcinoma [J]. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi, 2010 , 24(18): 820- 822.
[35] Choi HJ, Eun JS, Kim BG, et al. Vitexin, an HIF-1alpha inhibitor, has anti-metastatic potential in PC12 cells[J]. Mol Cells, 2006, 22(3): 291- 299.
[36] Yasui H, Ito N, Yamamori T, et al. Induction of neurite outgrowth by alpha-phenyl-N-tert- butylnitrone through nitric oxide release and Ras-ERK pathway in PC12 cells[J]. Free Radic Res, 2010, 44(6): 645- 654.
[37] Leiser Y, Silverstein N, Blumenfeld A, et al. The induction of tuftelin expression in PC12 cell line during hypoxia and NGF-induced differentiation[J]. J Cell Physiol, 2011, 226(1): 165- 172.
[38] Berger I, Stahl S, Rychkova N, et al. VEGF receptors on PC12 cells mediate transient activation of ERK1/2 and Akt: comparison of nerve growth factor and vascular endothelial growth factor[J]. J Negat Results Biomed, 2006, 7(1): 5- 8.
[1]皇甫超申,许靖华,秦明周,等.亚硝酸盐与癌的关系[J].河南大学学报(自然科学版),2009, 39(1):35-41.
[2] Kleinbongard P, Dejam A, Lauer T, et al. Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals[J]. Free Radic Biol Med, 2003, 35(7): 790- 796.
[3] Bryan NS, Fernandez BO, Bauer SM, et al. Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues[J]. Nat Chem Biol, 2005, 1(5): 290- 297.
[4] Ichihara T, Miyashita K, Kawabe M, et al. Lack of combination hepatocarcinogenicity of harman, norharman and amitrole when given with NaNO_2 in the rat[J]. J Toxicol Sci, 2005, 30(1): 1 - 6.
[5] Ward MH, deKok TM, Levallois P, et al. Workgroup report: Drinking-water nitrate and health recent findings and research needs[J]. Environ Health Perspect, 2005, 113(11): 1607- 1614.
[6] Wu X, Du L, Xu X ,et al. Increased nitrosoglutathione reductase activity in hypoxic pulmonary hypertension in mice [J]. J Pharmacol Sci, 2010, 113(1): 32- 40.
[7] Elmore E, Lao XY, Kapadia R, et al. Threshold-type dose response for induction of neoplastic transformation by 1 GeV/nucleon iron ions[J]. Radiat Res, 2009 , 171(6): 764- 770.
[8] Lundberg JO,Govoni M. Inorganic nitrate is a possible source for systemic generation of nitric oxide[J]. Free Radic Biol Med, 2004, 37 (3):395- 400.
[9] Bryan NS, Rassaf T, Maloney RE, et al. Cellular targets and mechanisms of nitros(yl)ation: an insight into their nature and kinetics in vivo[J]. Proc Natl Acad Sci USA, 2004, 101(12): 4308- 4313.
[10] Rodriguez J, Maloney RE, Rassaf T, et al. Chemical nature of nitric oxide storage forms in rat vascular tissue[J]. Proc Natl Acad Sci USA, 2003, 100(1): 336- 341.
[11] Dejam A, Hunter CJ, Pelletier MM, et al. Erythrocytes are the major intravascular storage sites of nitrite in human blood[J] . Blood, 2005, 106(2): 734- 739.
[12] Duranski MR, Greer JJ, Dejam A, et al . Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver[J].Clin Invest, 2005, 115(5): 1232- 1240 .
[13] Li H,SamouiIov A,Liu X,et a1.Characterization of the effects of oxygen on xanthine oxidase-mediated nitric oxide formation[J].Biol Chem, 2004, 279(17):16939- 16946.
[14] Bjorne H, Govoni M, Tornberg DC, et a1. Intragastric nitric oxide is abolished in intubated patients and restored by nitrite[J]. Crit Care Med, 2005, 33(8): 1722- 1727.
[15] Heiss C, Schanz A, Amabile N, et a1.Nitric oxide synthase expression and functional response to nitric oxide are both important modulators of circulating angiogenic cell response to angiogenic stimuli[J].?Arterioscler Thromb Vasc Biol, 2010, 30(11): 2212- 2218.
[16] Pellegrino D, Parisella ML.Nitrite as a physiological source of nitric oxide and a signalling molecule in the regulation of the cardiovascular system in both mammalian and non-mammalian vertebrates.Recent Pat Cardiovasc Drug Discov, 2010 ,5(2): 91- 96.
[17] Mantena SK, Vaughn DP, Andringa KK, et a1. High fat diet induces dysregulation of hepatic oxygen gradients and mitochondrial function in vivo[J].Biochem J. 2009 , 417(1): 183- 193.
[18] Raat NJ, Noguchi AC, liu VB, et al. Dietary nitrate and nitreite modulate blood and organ nitrite and the cellular ischemic stress response[J]. World Radic Biol Med, 2009, 47(5): 510- 517.
[19] Zaouali MA,Ben Mosbah I,Boncompagni E, et al.Hypoxia inducible factor-l alpha accumulation insteatotic liver preservation:role of nitric oxide[J]. World J Gastroentroenterol,2010,16(28): 3499-3509.
[20]昌平,刘芳,王春友,等.亚硝酸盐还原成一氧化氮保护肝脏对抗缺血再灌注损伤[J].世界华人消化杂志, 2005 ,13(3):346—350.
[21] Jung K H, Chu K, Ko S Y, et al. Early intravenous infusion of sodium nitrite protects brain against in vivo ischemia-reperfusion injury [ J ]. Stroke, 2006, 37( 11 ) : 2744- 2750.
[22] Gonzalez FM, Shiva S, Vincent PS, et al.Nitrite anion provides potent cytoprotective and antiapoptotic effects as adjunctive therapy to reperfusion for acute myocardial infarction[J]. Circulation, 2008, 117(23): 2986- 2994.
[23] Heusch P, Aker S, Boengler K, et al. Increased inducible nitric oxide synthase and arginase II expression in heart failure: no net nitrite/nitrate production and protein S-nitrosylation [J]. Am J Physiol Heart Circ Physiol, 2010, 299(2): 446- 453.
[24] Whiteman M, Rose P, Siau JL, et al. Nitrite-mediated protection against hypochlorous acid-induced chondrocyte toxicity: a novel cytoprotective role of nitric oxide in the inflamed joint?[J].Arthritis Rheum, 2003, 48(11): 3140- 3150.
[25] Suschek CV, Schroeder P, Aust O, et al. The presence of nitrite during UVA irradiation protects from apoptosis [J]. FASEB, 2003, 17(15): 2342- 2344.
[26] Shiva S, Gladwin MT. Nitrite mediates cytoprotection after ischemia/reperfusion by modulating mitochondrial function[J]. Basic Res Cardiol, 2009, 104(2): 113- 119.
[27] Kim-Shapiro DB, Gladwin MT, Patel RP, et al. The reaction between nitrite and hemoglobin: the role of nitrite in hemoglobin-mediated hypoxic vasAilation[J]. Inorg. Biochem, 2005, 99(1): 237- 246.
[28] Zuckerbraun BS, George P, Gladwin MT.Nitrite in pulmonary arterial hypertension: therapeutic avenues in the setting of dysregulated arginine/nitric oxide synthase signalling[J]. Cardiovasc Res, 2011, 89(3): 542- 552.
[29]张利鹏,杨敬平,孙德俊,等.雾化吸入亚硝酸钠对低氧性肺动脉高压大鼠肺动脉压力及NO、H_2S水平的影响[J].中国病理生理杂志,2010,26(1):122-126.
[30] Raat NJ, Shiva S, Gladwin MT. Effects of nitrite on modulating ROS generation following ischemia and reperfusion[J]. Adv Drug Deliv Rev, 2009, 61(4): 339- 350.
[31] Shiva S. Mitochondria as metabolizers and targets of nitrite[J]. Nitric Oxide. 2010, 22(2): 64- 74.
[32] Kim JW , Gao P , Liu YC , et al . Hypoxia inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase and pyruvate dehydrogenase kinase 1 [J ] . Mol Cell Biol , 2007 , 27(21: 7381- 7393.
[33] Nascarella M A ,Stanek E J,Hoffnann G R, et al.Quantification of hirmesis in anticancer-agent dose-respones[J] Dose Respinse,2009,7(2):160-70.
[34] Calaabrese E J.Hormesis, non-linearity, and risk communication [J]. Hum Exp Toxicol, 2009, 28(1): 5- 6.
[35]吴赤蓬,钟雪云.低剂量亚硝酸钠诱导CHL细胞DNA损伤的适应性反应[J].中国病理生理杂志,2008, 24 (6) : 1166 - 1172.
[36]李延红,史齐,石贞玉,等.低剂量亚硝酸钠预处理对H_2O_2损伤PC12细胞的保护作用[J].中国病理生理杂志,2010,26(4):802-808.
[37] Bol'shakova OI, Sverdlov AG, Timoshenko SI, et al. The influence of sAium nitrite on the osmoresistance of Chinese hamster cells[J]. Tsitologiia, 2007, 49(7): 576-580.
[38]孙玉生,史齐,李延红,等.低浓度亚硝酸钠对人肝癌SMMC-7721细胞的毒物兴奋效应[J].中国药理学通报,2010,26( 3) :419-420.
[39]史齐,李延红,皇甫超申,等.亚硝酸钠增强SMMC-7721细胞拮抗镉细胞毒性的研究[J].环境科学学报,2010 ,30(11):2270-2276.
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[43] Hardwick JB, Tucker AT, Wilks M, et al. A novel method for the delivery of nitric oxide therapy to the skin of human subjects using a semi-permeable membrane[J]. Clin Sci (Lond), 2001, 100(4):395-400.
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[45] Igueroa S, López E, Arce C, et al. SNAP, a NO donor, induces cellular protection only when cortical neurons are submitted to some aggression process[J]. Brain Res, 2005, 1034(1-2): 25- 33.
[2] Kleinbongard P, Dejam A, Lauer T, et al. Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals[J]. Free Radic Biol Med, 2003, 35(7): 790- 796.
[3] Bryan NS, Fernandez BO, Bauer SM, et al. Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues. Nat Chem Biol, 2005, 1(5): 290- 297.
[4] Weitzberg E, Hezel M, Lundberg JO.Nitrate-nitrite-nitric oxide pathway: implications for anesthesiology and intensive care[J]. Anesthesiology, 2010, 113(6): 1460- 1475.
[5] Jung KH, Chu K, Lee ST, et al.Effects of long term nitrite therapy on functional recovery in experimental ischemia model[J]. Biochem Biophys Res Commun, 2010, 403(1): 66- 72.
[6] Jung K H, Chu K, Ko S Y, et al. Early intravenous infusion of sodium nitrite protects brain against in vivo ischemia-reperfusion injury [ J ]. S troke, 2006, 37 ( 11 ) : 2744- 2750
[7] Heusch P, Aker S, Boengler K, et al. Increased inducible nitric oxide synthase and arginase II expression in heart failure: no net nitrite/nitrate production and protein S-nitrosylation[J]. Am J Physiol Heart Circ Physiol, 2010, 299(2): 446- 453.
[8] Liebmann J, Kolb-Bachofen V, Mahotka C, et al.Photolytically generated nitric oxide inhibits caspase activity and results in AIF-mediated cell death[J]. J Mol Med, 2010, 88(3): 279- 287.
[9] Whiteman M, Rose P, Siau JL, Halliwell B. Nitrite-mediated protection against hypochlorous acid-induced chondrocyte toxicity: a novel cytoprotective role of nitric oxide in the inflamed joint[J]?. Arthritis Rheum, 2003, 48(11): 3140- 3150.
[10] Mozaffari MS, Baban B, Liu JY, et al.Mitochondrial complex I and NAD(P)H oxidase are major sources of exacerbated oxidative stress in pressure-overloaded ischemic-reperfused hearts[J]. Basic Res Cardiol, 2011, 106(2): 287- 297.
[11] Singh M, Shukla D, Thomas P, et al.Hypoxic preconditioning facilitates acclimatization to hypobaric hypoxia in rat heart[J].J Pharm Pharmacol, 2010, 62(12): 1729- 1739.
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[13] Bos R, van Diest PJ, van der Groep P, et al. Expression of hypoxia-inducible factor1alpha and cell cycle proteins in invasive breast cancer are estrogen receptor related. Breast Cancer Res , 2004, 6(4): 450- 459.
[14] Liu LP, Liao ZP, Yin D, et al.The protective effects of Polygonum multiflorum stilbeneglycoside preconditioning in an ischemia/reperfusion model of HUVECs[J]. Acta Pharmacol Sin, 2010 ,31(4): 405- 412.
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[17] Yamanaka Y, Yoshida S.NGF-induced neurite outgrowth of PC12 cells in the presence of phosphatidylcholine hydroperoxides: Implication for ageing[J].Doi H. Mech Ageing Dev, 2008,129(4): 215- 222.
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[24] Saijo F, Milsom AB, Bryan NS , et al.On the dynamics of nitrite, nitrate and other biomarkers of nitric oxide production in inflammatory bowel disease [J]. Nitric Oxide, 2010, 22(2): 155- 167.
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[26] Raat NJ, Shiva S, Gladwin MT. Effects of nitrite on mAulating ROS generation following ischemia and reperfusion[J]. Adv Drug Deliv Rev, 2009 , 61(4): 339- 350.
[27] Shiva S. Mitochondria as metabolizers and targets of nitrite[J]. Nitric Oxide, 2010, 22(2): 64- 74.
[28] Rhenals MV, Strasberg-Rieber M, Rieber M, et al . Nitric oxide donors or nitrite counteract copper-[dithiocarbamate](2)-mediated tumor cell death and inducible nitric oxide synthase down-regulation: possible role of a nitrosyl-copper [dithiocarbamate](2) complex[J]. J Med Chem, 2010 , 53(4): 1627- 1635.
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[32] Zaouali MA, Ben Mosbah I, Boncompagni E, et al. Hypoxia inducible factor-1alpha ac-cumulation in steatotic liver preservation: role of nitric oxide. World J Gastroenterol, 2010 , 16(28): 3499- 3509.
[33] Sun D, Liu CX, Ma YY, et al . Protective effect of prostaglandin e1 on renal microvascular injury in rats of acute aristolochic Acid nephropathy[J]. Ren Fail, 2011, 33(2): 225- 232.
[34] Cheng W, Zhou W. Clinical significance and relationship between HIF-1alpha, COX-2, VEGF and microvessel density expression in laryngeal carcinoma [J]. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi, 2010 , 24(18): 820- 822.
[35] Choi HJ, Eun JS, Kim BG, et al. Vitexin, an HIF-1alpha inhibitor, has anti-metastatic potential in PC12 cells[J]. Mol Cells, 2006, 22(3): 291- 299.
[36] Yasui H, Ito N, Yamamori T, et al. Induction of neurite outgrowth by alpha-phenyl-N-tert- butylnitrone through nitric oxide release and Ras-ERK pathway in PC12 cells[J]. Free Radic Res, 2010, 44(6): 645- 654.
[37] Leiser Y, Silverstein N, Blumenfeld A, et al. The induction of tuftelin expression in PC12 cell line during hypoxia and NGF-induced differentiation[J]. J Cell Physiol, 2011, 226(1): 165- 172.
[38] Berger I, Stahl S, Rychkova N, et al. VEGF receptors on PC12 cells mediate transient activation of ERK1/2 and Akt: comparison of nerve growth factor and vascular endothelial growth factor[J]. J Negat Results Biomed, 2006, 7(1): 5- 8.
[1]皇甫超申,许靖华,秦明周,等.亚硝酸盐与癌的关系[J].河南大学学报(自然科学版),2009, 39(1):35-41.
[2] Kleinbongard P, Dejam A, Lauer T, et al. Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals[J]. Free Radic Biol Med, 2003, 35(7): 790- 796.
[3] Bryan NS, Fernandez BO, Bauer SM, et al. Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues[J]. Nat Chem Biol, 2005, 1(5): 290- 297.
[4] Ichihara T, Miyashita K, Kawabe M, et al. Lack of combination hepatocarcinogenicity of harman, norharman and amitrole when given with NaNO_2 in the rat[J]. J Toxicol Sci, 2005, 30(1): 1 - 6.
[5] Ward MH, deKok TM, Levallois P, et al. Workgroup report: Drinking-water nitrate and health recent findings and research needs[J]. Environ Health Perspect, 2005, 113(11): 1607- 1614.
[6] Wu X, Du L, Xu X ,et al. Increased nitrosoglutathione reductase activity in hypoxic pulmonary hypertension in mice [J]. J Pharmacol Sci, 2010, 113(1): 32- 40.
[7] Elmore E, Lao XY, Kapadia R, et al. Threshold-type dose response for induction of neoplastic transformation by 1 GeV/nucleon iron ions[J]. Radiat Res, 2009 , 171(6): 764- 770.
[8] Lundberg JO,Govoni M. Inorganic nitrate is a possible source for systemic generation of nitric oxide[J]. Free Radic Biol Med, 2004, 37 (3):395- 400.
[9] Bryan NS, Rassaf T, Maloney RE, et al. Cellular targets and mechanisms of nitros(yl)ation: an insight into their nature and kinetics in vivo[J]. Proc Natl Acad Sci USA, 2004, 101(12): 4308- 4313.
[10] Rodriguez J, Maloney RE, Rassaf T, et al. Chemical nature of nitric oxide storage forms in rat vascular tissue[J]. Proc Natl Acad Sci USA, 2003, 100(1): 336- 341.
[11] Dejam A, Hunter CJ, Pelletier MM, et al. Erythrocytes are the major intravascular storage sites of nitrite in human blood[J] . Blood, 2005, 106(2): 734- 739.
[12] Duranski MR, Greer JJ, Dejam A, et al . Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver[J].Clin Invest, 2005, 115(5): 1232- 1240 .
[13] Li H,SamouiIov A,Liu X,et a1.Characterization of the effects of oxygen on xanthine oxidase-mediated nitric oxide formation[J].Biol Chem, 2004, 279(17):16939- 16946.
[14] Bjorne H, Govoni M, Tornberg DC, et a1. Intragastric nitric oxide is abolished in intubated patients and restored by nitrite[J]. Crit Care Med, 2005, 33(8): 1722- 1727.
[15] Heiss C, Schanz A, Amabile N, et a1.Nitric oxide synthase expression and functional response to nitric oxide are both important modulators of circulating angiogenic cell response to angiogenic stimuli[J].?Arterioscler Thromb Vasc Biol, 2010, 30(11): 2212- 2218.
[16] Pellegrino D, Parisella ML.Nitrite as a physiological source of nitric oxide and a signalling molecule in the regulation of the cardiovascular system in both mammalian and non-mammalian vertebrates.Recent Pat Cardiovasc Drug Discov, 2010 ,5(2): 91- 96.
[17] Mantena SK, Vaughn DP, Andringa KK, et a1. High fat diet induces dysregulation of hepatic oxygen gradients and mitochondrial function in vivo[J].Biochem J. 2009 , 417(1): 183- 193.
[18] Raat NJ, Noguchi AC, liu VB, et al. Dietary nitrate and nitreite modulate blood and organ nitrite and the cellular ischemic stress response[J]. World Radic Biol Med, 2009, 47(5): 510- 517.
[19] Zaouali MA,Ben Mosbah I,Boncompagni E, et al.Hypoxia inducible factor-l alpha accumulation insteatotic liver preservation:role of nitric oxide[J]. World J Gastroentroenterol,2010,16(28): 3499-3509.
[20]昌平,刘芳,王春友,等.亚硝酸盐还原成一氧化氮保护肝脏对抗缺血再灌注损伤[J].世界华人消化杂志, 2005 ,13(3):346—350.
[21] Jung K H, Chu K, Ko S Y, et al. Early intravenous infusion of sodium nitrite protects brain against in vivo ischemia-reperfusion injury [ J ]. Stroke, 2006, 37( 11 ) : 2744- 2750.
[22] Gonzalez FM, Shiva S, Vincent PS, et al.Nitrite anion provides potent cytoprotective and antiapoptotic effects as adjunctive therapy to reperfusion for acute myocardial infarction[J]. Circulation, 2008, 117(23): 2986- 2994.
[23] Heusch P, Aker S, Boengler K, et al. Increased inducible nitric oxide synthase and arginase II expression in heart failure: no net nitrite/nitrate production and protein S-nitrosylation [J]. Am J Physiol Heart Circ Physiol, 2010, 299(2): 446- 453.
[24] Whiteman M, Rose P, Siau JL, et al. Nitrite-mediated protection against hypochlorous acid-induced chondrocyte toxicity: a novel cytoprotective role of nitric oxide in the inflamed joint?[J].Arthritis Rheum, 2003, 48(11): 3140- 3150.
[25] Suschek CV, Schroeder P, Aust O, et al. The presence of nitrite during UVA irradiation protects from apoptosis [J]. FASEB, 2003, 17(15): 2342- 2344.
[26] Shiva S, Gladwin MT. Nitrite mediates cytoprotection after ischemia/reperfusion by modulating mitochondrial function[J]. Basic Res Cardiol, 2009, 104(2): 113- 119.
[27] Kim-Shapiro DB, Gladwin MT, Patel RP, et al. The reaction between nitrite and hemoglobin: the role of nitrite in hemoglobin-mediated hypoxic vasAilation[J]. Inorg. Biochem, 2005, 99(1): 237- 246.
[28] Zuckerbraun BS, George P, Gladwin MT.Nitrite in pulmonary arterial hypertension: therapeutic avenues in the setting of dysregulated arginine/nitric oxide synthase signalling[J]. Cardiovasc Res, 2011, 89(3): 542- 552.
[29]张利鹏,杨敬平,孙德俊,等.雾化吸入亚硝酸钠对低氧性肺动脉高压大鼠肺动脉压力及NO、H_2S水平的影响[J].中国病理生理杂志,2010,26(1):122-126.
[30] Raat NJ, Shiva S, Gladwin MT. Effects of nitrite on modulating ROS generation following ischemia and reperfusion[J]. Adv Drug Deliv Rev, 2009, 61(4): 339- 350.
[31] Shiva S. Mitochondria as metabolizers and targets of nitrite[J]. Nitric Oxide. 2010, 22(2): 64- 74.
[32] Kim JW , Gao P , Liu YC , et al . Hypoxia inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase and pyruvate dehydrogenase kinase 1 [J ] . Mol Cell Biol , 2007 , 27(21: 7381- 7393.
[33] Nascarella M A ,Stanek E J,Hoffnann G R, et al.Quantification of hirmesis in anticancer-agent dose-respones[J] Dose Respinse,2009,7(2):160-70.
[34] Calaabrese E J.Hormesis, non-linearity, and risk communication [J]. Hum Exp Toxicol, 2009, 28(1): 5- 6.
[35]吴赤蓬,钟雪云.低剂量亚硝酸钠诱导CHL细胞DNA损伤的适应性反应[J].中国病理生理杂志,2008, 24 (6) : 1166 - 1172.
[36]李延红,史齐,石贞玉,等.低剂量亚硝酸钠预处理对H_2O_2损伤PC12细胞的保护作用[J].中国病理生理杂志,2010,26(4):802-808.
[37] Bol'shakova OI, Sverdlov AG, Timoshenko SI, et al. The influence of sAium nitrite on the osmoresistance of Chinese hamster cells[J]. Tsitologiia, 2007, 49(7): 576-580.
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