砷及MPST过表达对SH-SY5Y细胞GRP78/CHOP通路的影响

目的探讨内质网应激是否参与亚砷酸钠(NaAsO2)神经毒性损伤,明确3-巯基丙酮酸硫转移酶(3-mercaptopyruvate sulfurtransferase,MPST)过表达是否调节砷诱导的内质网应激。方法通过构建MPST基因慢病毒表达载体来获得稳定表达外源MPST基因的SH-SY5Y细胞株作为SH-MPST过表达组,另设空载体转染细胞为SH-PEB组,染砷组(NaAsO2组),内质网应激阻断剂TUDCA组,TUDCA预处理染砷组。Western blot法分别检测过表达MPST、染砷及TUDCA预处理后细胞内GRP78和CHOP蛋白表达的变化。结果单纯MPST过表达不影响SH-SY5Y细胞内GRP78、CHOP蛋白的表达水平;经NaAsO2处理后,SH-PEB细胞内GRP78、CHOP蛋白明显上调(P<0.01),而被内质网应激阻断剂TUDCA所拮抗;MPST过表达则抑制砷对GRP78、CHOP蛋白的上调(P<0.01);然而,TUDCA预处理则明显逆转MPST过表达对GRP78、CHOP蛋白的影响(P<0.01)。结论GRP78/CHOP内质网应激通路参与了砷诱导的神经毒性损伤;MPST过表达可降低砷诱导的内质网应激水平。     

Molecular Mechanisms of Hydrogen Sulfide Toxicity

Rationale. The toxicity of H2S has been attributed to its ability to inhibit cytochrome c oxidase in a similar manner to HCN. However, the successful use of methemoglobin for the treatment of HCN poisoning was not successful for H2S poisonings even though the ferric heme group of methemoglobin scavenges H2S. Thus, we speculated that other mechanisms contribute to H2S induced cytotoxicity. Experimental procedure. Hepatocyte isolation and viability and enzyme activities were measured as described by , and . Results. Incubation of isolated hepatocytes with NaHS solutions (a H₂S source) resulted in glutathione (GSH) depletion. Moreover, GSH depletion was also observed in TRIS-HCl buffer (pH 6.0) treated with NaHS. Several ferric chelators (desferoxamime and DETAPAC) and antioxidant enzymes (superoxide dismutase [SOD] and catalase) prevented cell-free and hepatocyte GSH depletion. GSH-depleted hepatocytes were very susceptible to NaHS cytotoxicity, indicating that GSH detoxified NaHS or H₂S in cells. Cytotoxicity was also partly prevented by desferoxamine and DETAPC, but it was increased by ferric EDTA or EDTA. Cell-free oxygen consumption experiments in TRIS-HCl buffer showed that NaHS autoxidation formed hydrogen peroxide and was prevented by DETAPC but increased by EDTA. We hypothesize that H₂S can reduce intracellular bound ferric iron to form unbound ferrous iron, which activates iron. Additionally, H₂S can increase the hepatocyte formation of reactive oxygen species (ROS) (known to occur with electron transport chain). H₂S cytotoxicity therefore also involves a reactive sulfur species, which depletes GSH and activates oxygen to form ROS.     

益肾活血方联合氯沙坦对维持性血液透析患者内源性硫化氢及炎症细胞因子的影响

目的:观察益肾活血方联合氯沙坦治疗对维持性血液透析患者内源性硫化氢、炎症细胞因子以及血管内皮细胞功能的影响。方法:将90例维持性血液透析患者随机抽样法分为益肾活血方组、氯沙坦组、联合用药组,每组各30例,检测患者治疗前后血清总胆固醇(TC),甘油三脂(TG),低密度脂蛋白(LDL-C),同型半胱氨酸(Hcy),高敏C反应蛋白(hs-CRP),硫化氢(H2S),硫化血红蛋白(SHb),血浆内皮素(ET-1),一氧化氮(NO),肿瘤坏死因子α(TNF-α),白介素6(IL-6)水平和血流介导性内皮舒张功能(FMD)。结果:联合用药组[TC(3.68±0.85)mmol·L-1,LDL-C(2.07±1.61)mmol·L-1,Hcy(31.76±17.23)μmol·L-1]水平较治疗前明显下降[(5.29±1.28)mmol·L-1,(3.45±1.84)mmol·L-1,(35.97±18.23)μmol·L-1],差异具统计学意义(P0.05);hs-CRP(15.23±4.01)mg·L-1,H2S(9.81±5.61)nmol·L-1,SHb(5.58±1.29)%,ET-1(20.77±10.01)ng·mol-1,NO(17.42±8.81)μmol·L-1,TNF-α(39.6±6.53)ng·L-1,IL-6(37.6±3.51)ng·L-1水平和FMD(10.05±.3.56)%较治疗前显著改善[(19.13±6.18)mg·L-1,(5.51±3.24)nmol·L-1,(2.04±0.49)%,(25.39±14.26)ng·mol-1,(13.14±6.59)μmol·L-1,(42.4±7.61)ng·L-1,(40.6±4.62)ng·L-1,(6.67±1.94)%],差异有统计学意义(P0.01)。结论:益肾活血方联合氯沙坦能显著改善维持性血透患者血管内皮细胞功能损伤。     

豆腐制硫黄过程中所产生的黑色物质成因初探

探讨了硫黄炮制过程中豆腐显黑绿色的原因,还对炮制过程中产生的使豆腐显黑绿色的物质进行了X衍射物相分析和化学定性分析,在此基础上对硫黄的炮制工艺、炮制容器等问题进行了讨论。     

Hazards after the storm: Floodwater drainage pump stations and exposure to hydrogen sulfide

A hurricane can present unique hazards that exist long after the strong winds and heavy rains have subsided. These hazards may not only be physical, but chemical as well. Hydrogen sulfide (H₂S) represents an important and potentially overlooked hazard that can be naturally produced in floodwaters following a hurricane. In August of 2012, in the wake of Hurricane Isaac, Plaquemines Parish, Louisiana was submerged under a blanket of floodwater. To remove floodwaters that had breached the levee system designed to keep water out, temporary drainage pump stations were installed at strategic locations. The transfer of floodwaters at these drainage stations resulted in the generation of elevated concentrations of airborne H₂S at the pumping stations. The generation of H₂S at these pumping stations represented a potential inhalation hazard for workers; thus, awareness for possible H₂S exposure at these installments is crucial.     

Role of cytochrome P4502E1 in alcoholic liver disease pathogenesis

The intragastric tube feeding model is ideal for the study of the role of dietary factors and the effect of drugs on experimental alcoholic liver disease (ALD), since the model allows us to study the effect of a single variable in the diet on the pathology of liver where the blood alcohol level (BAL) is maintained over 150 mg%. By varying the dietary fatty acid composition we showed that the pathology was worsened by increasing linoleic acid or polyunsaturated fatty acids (PUFAs) in the diet where cytochrome P4502E1 (CYP2E1) was increased posttranslationally by high BAL. Concomitant with the increase in CYP2E1 there was evidence for an increase in lipid peroxidation (LP) by microsomes. Protein adducts of the products of LP were increased in the blood. Isoniazid (INH) enhanced this process and the pathology of ALD when INH was fed at therapeutic levels with ethanol. Preliminary studies show that diallyl sulfide, which inhibits and destroys liver CYP2E1 selectively, also modified the pathologic effects of ethanol. Thus we postulate that CYP2E1 induction plays a central role in the pathogenesis of ALD.     

A High‐Sensitivity Coumarin‐Based Fluorescent Probe for Monitoring Hydrogen Sulfide in Living Cells

A novel coumarin‐based fluorescence probe has been constructed for the selective and sensitive detection of hydrogen sulfide (H₂S). This probe displays high sensitivity and linearity to H₂S in degassed PBS buffers and fetal bovine serum. It reacts with H₂S with high selectivity over Cys, GSH, and other anions. Meanwhile, successful detection of H₂S in living cells was also demonstrated.     

Toxic trace elements at gastrointestinal level

Many trace elements are considered essential [iron (Fe), zinc (Zn), copper (Cu)], whereas others may be harmful [lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As)], depending on their concentration and chemical form. In most cases, the diet is the main pathway by which they enter our organism. The presence of toxic trace elements in food has been known for a long time, and many of the food matrices that carry them have been identified. This has led to the appearance of legislation and recommendations concerning consumption. Given that the main route of exposure is oral, passage through the gastrointestinal tract plays a fundamental role in their entry into the organism, where they exert their toxic effect. Although the digestive system can be considered to be of crucial importance in their toxicity, in most cases we do not know the events that occur during the passage of these elements through the gastrointestinal tract and of ascertaining whether they may have some kind of toxic effect on it. The aim of this review is to summarize available information on this subject, concentrating on the toxic trace elements that are of greatest interest for organizations concerned with food safety and health: Pb, Cd, Hg and As.     

Postranslational Modification of Ion Channels in Colonic Inflammation

Voltage-gated ion channels are key regulators of cell excitability. There is significant evidence that these channels are subject to modulation by redox status of the cells. Here we review the post-translational modifications of ion channels that occur in colonic inflammation. The redox mechanisms involve tyrosine nitration, covalent modification of cysteine residues and sulfhydration by hydrogen sulfide in experimental colitis. In the setting of colonic inflammation, modifications of cysteine and tyrosine are likely to occur at several sites within the same channel complex. In this review we describe alterations in channel function due to specific modifications of tyrosine and cysteine residues by reactive nitrogen, oxygen and hydrogen-sulfide resulting in altered motility.