The Sod2 mutant mouse as a model for oxidative stress: A functional proteomics perspective

Oxidative stress has been implicated in the pathogenesis of numerous human diseases and disorders, but the mechanistic basis often remains enigmatic. The Sod2 mutant mouse, which is sensitized to mitochondrial stress, is an ideal mutant model for studying the role of oxidative stress in a diverse range of complications arising from mitochondrial dysfunction and diminished antioxidant defense. To fully appreciate the widespread molecular consequences under increased oxidative stress, a systems approach utilizing proteomics is able to provide a global overview of the complex biological changes, which a targeted single biomolecular approach cannot address fully. This review focuses on the applications of mass spectrometry and functional proteomics in the Sod2 mouse. The combinatorial approach provides novel insights into the interplay of chemistry and biology, free radicals and proteins, thereby augmenting our understanding of how redox perturbations influence protein dynamics. Ultimately, this knowledge can lead to the development of free radical‐targeted therapies. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:179–196, 2010     

Observation of the surface stress induced in microcantilevers by electrochemical redox processes

The potential-induced surface stress of a solid electrode was investigated in an electrochemical cell. Gold-coated atomic force microscopy microcantilevers were used as working electrodes to measure the current–potential response (by cyclic voltammetry) and simultaneous bending characteristics in solutions of NaNO₃ and K₃Fe(CN)₆/NaNO₃. The observed changes of differential surface stress at a microcantilever electrode were attributed to electrochemical-potential-induced changes in surface charge density, ion adsorption/desorption, and electron transfer across the electrode surface. The potential dependent change in stress shows promise for the study of microscopic properties at the solid–electrolyte interface.     

浅析砝码作为计量标准器对测量不确定度的贡献

本文主要介绍了砝码检定引入的标准不确定度的计算。     

α-腈基阿魏酸及其二元混合基体在基体辅助激光解吸/电离飞行时间质谱法测定蛋白质中的应用

本文应用自行设计、制备的新基体α－腈基阿魏酸及α－腈基阿魏酸与３－硝基苄醇组成的固液相二元混合基体,用基体辅助激光解吸／电离飞行时间质谱法成功地对蛋白质样品胰岛素,细胞色素Ｃ和白蛋白进行了分子量测定。研究结果表明,α－腈基阿魏酸可以有效地解吸分子量较小的胰岛素,而α－腈基阿魏酸与３－硝基苄醇组成的二元混合基体则能够明显地提高分析灵敏度和重现性,测得分子量较大的细胞色素Ｃ和白蛋白的激光质谱图     

Current analytical methods for the detection of dityrosine, a biomarker of oxidative stress, in biological samples

Dityrosine is a fluorescent molecule formed as a result of normal posttranslational processing. In many structural proteins, dityrosine confers resistance to proteolysis and physicochemical trauma as a stabilizing crosslink. Dityrosine has also been found in oxidative/nitrative stress under a variety of conditions and biological systems. In this regard, it has been used as an important biomarker for oxidatively modified proteins during UV and gamma-irradiation, aging, and exposure to oxygen free radicals, nitrogen dioxide, peroxynitrite, and lipid hydroperoxides. Renewed interest in dityrosine and other tyrosine oxidation products as clinical indicators of oxidative modification has driven the development of important techniques for the specific analysis and quantification of these molecules. The presence of elevated levels of dityrosine in mammalian tissue and urine samples has been measured by chromatographic separation followed by mass spectrometry GC-MS and HPLC-MS/MS. Increases in dityrosine levels have been associated with pathologies such as eye cataracts, atherosclerosis, acute inflammation, and Alzheimer's disease. The continued development of, and increased accessibility to, improved mass spectrometric instrumentation will expand the capability, feasibility, and sensitivity with which specific biomarkers like dityrosine can be measured.     

Imaging of Proteins in Tissue Sections Using Mass Spectrometry as a Discovery Tool

The Mass Spectrometry Group of Richard M. Caprioli at Vanderbilt University is evaluating MacromizerTM for their MALDI-imaging application. The expectation is to see more high mass proteins due to the increased high mass sensitivity of MacromizerTM.     

Boldine provides protective effect against nephrotoxicity induced by cisplatin in Wistar rats: Role of oxidative stress,inflammation and caspase-3

Side effects of cisplatin, especially dose-dependent nephrotoxicity, are major factors limiting its use in cancer.Boldine ((S)-2, 9-dihydroxy-1, 10-dimethoxy-aporphine) is a natural alkaloid known for its strong antioxidant activitypresent in leaves/bark of boldo tree (Peumus boldus Molina), a native tree in Chile. Here, we aimed to investigate thenephroprotective effect of boldine and its underlying mechanisms on cisplatin-induced rat renal injury. Thirty Wistaralbino rats divided into 5 groups (Control, Cis, Bold.40, Cis + Bold.20, Cis + Bold.40 groups) were used. Rats receivedboldine (20 or 40 mg/kg/day), or vehicle (saline) intraperitoneal for 14 days and a single dose cisplatin (7 mg/kg, ip)was applied on the 10th day to induce nephrotoxicity. Rats and kidney tissue were weighed to determine kidneyindex. Blood urea nitrojen (BUN) and creatinine levels, the amount of thiobarbituric acid reactive substances (TBARS,an index of lipid peroxidation), superoxide dismutase (SOD), glutathione peroxidase (GPx) enzyme activities andtumor necrosis factor alpha (TNF-α) levels were measured and histopathologic examination was performed. Induciblenitric oxide synthase (iNOS) and caspase-3 expressions were detected immunohistochemically. Nephrotoxicityinduced by cisplatin was apparent by elevated levels of BUN, creatinine, kidney index, TBARS and TNF-α, anddecreased body weight, SOD and GPx enzyme levels. Pretreatment with boldine protected the renal function at bothboldine doses by fixing the renal damage markers, oxidative stress, caspase-3 and iNOS expression. Histopathologicalfindings supported biochemical findings. Taken together these findings indicate that boldine has promising protectiveeffect against cisplatin nephrotoxicity by improving oxidative stress, inflammation, histopathological alterations andby alleviating caspase 3 expression.     

Investigation of the antioxidant defensive role of both AD-MSCs and BM-MSCs in modulating the alteration in the oxidative stress status in various STZ-diabetic rats’ tissues

Diabetes mellitus (DM) could negatively affect patients’ health via inducing a lot of serious functional hazards in many tissues’ cells at molecular levels. Recently, many scientists had proposed stem cell therapy being an appropriate alternative treatment protocol for numerous health threatening issues including diabetes. Therefore, the current study was designed to investigate the antioxidant potentiality of two MSCs types in alleviating tissues’ oxidative stress dramatic elevation resulting as a consequence of Type 1 DM induction. In our 4 weeks study, animals were divided into four groups: control group, STZ-diabetic group (D), D+AD-MSCs group and D+BM-MSCs group. Data reported that diabetic rats treated with either AD-MSCs or BM-MSCs exhibited a marvelous body tissues (Pancreas, Liver and Kidney) enhancing capabilities in attenuating the oxidative stress status; as evidenced by XO, ROS, and MDA levels down-regulation; with a general concomitant elevation in the antioxidants’ content; evidenced by many enzymatic and non-enzymatic antioxidants up-regulation; relative to the diabetic untreated group. Interestingly, comparing both treatments with each other and to control group, most of the measured parameters were reverted back to near normal levels after AD-MSCs injection; which clearly point out their stunning health benefits and superiority as anti-diabetic agent in overcoming different tissues’ complications; owing to their marked cytoprotective and regenerative potentialities.     

傅立叶变换-离子回旋共振质谱法在蛋白质分析中的应用

对傅立叶变换 -离子回旋共振质谱 (FT/ICRMS)的仪器特点及 FT/ICRMS在研究蛋白质结构鉴定、蛋白质翻译后修饰和蛋白组学中的应用等方面进行了综述和讨论。给出参考文献 4 5篇     

SiCf–SiBC composites: microstructural investigations of the as-received material and creep tested composites under an oxidative environment

SiC_f–SiBC composites fabricated by Snecma Propulsion Solide (St Médard en Jalles, France) were investigated by SEM and HRTEM in the as‐received state and after creep tests performed in air, in a temperature range 1423–1573 K, under 170 and 200 MPa. These composites are reinforced by Hi‐Nicalon fibres (Nippon Carbon). A pyrocarbon interphase was first deposited on the fibres. The matrix was then deposited on the fibrous preform by several chemical vapour infiltrations (CVI). As a result the matrix is multilayered and based on the Si–B–C ternary system. This matrix is self‐sealing: this is due to the presence of boron inducing the formation of a sealant glass if the material is heated in an oxidative environment. This glass will protect fibres and fibre/matrix interphases against oxidation. Hi‐Nicalon fibres as well as the different matrix layers were studied by HRTEM and EDX. Some investigations were carried out on the creep‐tested specimens in order to characterize modifications observed in the different constituents of the composites, particularly at the interfaces between the matrix layers and at the fibre/matrix interface. It was shown that several matrix layers crystallized during the creep tests. Moreover, a thin silica layer was observed at the pyrocarbon/matrix interfaces. Differences between the behaviour of the same type of material creep tested under neutral atmosphere are discussed.     

Changes in the redox status of the brain in an experimental glaucoma model

The purpose of this study was to evaluate the redox status changes of primary visual targets in the rat brain of a high pressure-induced glaucoma model. The animal model consisted of inducing ocular hypertension by cauterizing two episcleral veins on the left eye. The markers of oxidative damage and the oxidative balance evaluated in the brain seven days postoperative were: nitrites concentration, levels of non-enzymatic antioxidants and antioxidant enzymes activity.
The increase in the nitrite content, which could be the result of the enhancement in the production of nitrogen species, and in the activity of NADPH oxidase in the glaucoma group could lead to an increase on lipid and protein damage.
The decrease on the non-enzymatic antioxidants and the compensatory increase of the superoxide dismutase and glutathione peroxidase activities could be a consequence of the increase of oxidative processes. The decrease in the activity of glutathione reductase leads to a decrease in the recycling of thiol groups.
We suggest that oxidative stress can possibly acts as a risk factor for neurodegeneration in the brain. Therapeutic strategies to stop the progression of the disease in glaucoma should also be considered the central neuronal degeneration beyond the retina and the optic nerve.     

基于质谱的蛋白质绝对定量研究策略和建议

科学家已经研究获得了大量的蛋白质/多肽潜在生物标志物,这些生物标志物需要经过验证和确证才能进一步转化到临床应用.针对蛋白质/多肽的绝对定量研究在标志物验证和确证过程中起到关键作用.传统的蛋白质定量方法,如酶联免疫吸附试验(ELISA)技术存在蛋白质抗体难以获得、不同抗体批次之间存在差异、基于抗体的检测存在交叉反应等问题...     

Protective effect of aqueous suspension of dried latex of Calotropis procera against oxidative stress and renal damage in diabetic rats

Calotropis species have been used in the traditional medicinal system for the treatment of diseases of the liver and abdomen. In view of the antioxidant and anti-hyperglycemic properties of an aqueous suspension obtained from the dried latex of Calotropis procera, the present study was carried out to evaluate its efficacy in affording protection against alloxan induced changes in rat kidney. A single intraperitoneal injection of alloxan (150 mg/kg) in rats produced hyperglycemia within 3 days and altered kidney functions over a period of 90 days. Daily oral administration of the aqueous suspension (100 and 400 mg/kg) in diabetic rats produced anti-hyperglycemic effect that was comparable to that of glibenclamide (10 mg/kg). Unlike glibenclamide, the aqueous suspension did not increase the serum insulin levels in diabetic rats. However, it produced a marked reduction in the levels of urinary glucose and protein and normalized the renal tissue levels of thiobarbituric acid-reactive substances (TBARS) and glutathione (GSH) in diabetic rats and the effect was comparable to that of glibenclamide. The protection afforded by the aqueous suspension was also evident from the histological analysis of the renal tissue. Our study shows that by exhibiting antioxidant and anti-hyperglycemic property the aqueous suspension of dried latex of C. procera affords protection against the complications associated with diabetes.     

Mo/Si多层膜残余应力的研究

在极紫外光刻技术中,光学系统对多层膜光学元件表面面形精度有严格的要求,并且多层膜光学元件需要较高的反射率.由于多层膜中存在的内应力将改变光学元件的表面面形,因此在不减少反射率的前提下,一定要减少或补偿多层膜内的残余应力.论述了Mo/Si多层膜应力产生的原因和几种减少与补偿应力的技术,介绍应力的几种测量方法.     

Mesenchymal stem cell-derived exosomes as new remedy for the treatment of inflammatory eye diseases

Detrimental immune response has a crucially important role in the development and progression of inflammatory eye diseases. Inflammatory mediators and proteolytic enzymes released by activated immune cells induce serious injury of corneal epithelial cells and retinal ganglion cell which may result in the vision loss. Mesenchymal stem cells (MSCs) are regulatory cells which produce various immunosuppressive factors that modulate phenotype and function of inflammatory immune cells. However, several safety issues, including undesired differentiation and emboli formation, limit clinical use of MSCs. MSC-derived exosomes (MSC-Exos) are nano-sized extracellular vesicles which contain all MSC-derived immunoregulatory factors. Intraocular administration of MSC-Exos efficiently attenuated eye inflammation and significantly improved visual acuity in experimental animals without causing any severe side effects. As cell-free product, MSC-Exos addressed all safety issues related to the transplantation of MSCs. Therefore, MSC-Exos could be considered as potentially new remedy for the treatment of inflammatory eye diseases which efficacy should be explored in up-coming clinical trials.     

Aged garlic extract ameliorates the oxidative stress,histomorphological, and ultrastructural changes of cisplatin‐induced nephrotoxicity in adult male rats

Aim: Aged garlic extract (AGE) is a natural dietary substance having different antioxidant free‐radical‐scavenger compounds that ameliorates the toxicity of the oxidative stress. This study aimed to investigate the effect of AGE on cisplatin (CP)‐induced nephrotoxicity in rats. Materials and Methods: Twenty‐four, adult male Wistar albino rats were randomly divided into four groups namely control, AGE‐treated (a single oral dose of 250 mg/kg/day for 21 days), CP‐treated (a single intraperitoneal dose of 7.5 mg/kg on Day 16), and AGE + CP‐treated (AGE at a dose of 250 mg/kg/once daily for 21 days and a single dose of CP of 7.5 mg/kg intraperitoneally on Day 16). Body weight and absolute and relative kidney weights of each rat were calculated. Serum creatinine, uric acid, and urea levels were determined. Level of malondialdehyde and reduced glutathione and activity of superoxide dismutase and catalase of renal tissues were measured. Renal specimens from each rat were prepared for both light and electron microscopic examinations. Results: Interstitial cell infiltration, hemorrhage, glomerular atrophy, necrosis, and tubular degeneration were observed after CP treatment. Superoxide dismutase and catalase activities and glutathione level were significantly decreased and malondialdehyde level was significantly increased in CP‐treated rats compared with AGE + CP‐treated animals. A remarkable improvement in the histopathological and ultrastructural changes induced by CP in renal tissues was observed in AGE + CP‐treated rats. Conclusion: AGE exhibited antioxidant effect that could ameliorate the nephrotoxic effects of CP. Microsc. Res. Tech. 78:452–461, 2015. © 2015 Wiley Periodicals, Inc.