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1.
《Biochimica et Biophysica Acta (BBA)/General Subjects》2016,1860(7):1519-1527
BackgroundEtoposide and doxorubicin, topoisomerase II poisons, are important drugs for the treatment of tumors in the clinic. Topoisomerases contain several free sulfhydryl groups which are important for their activity and are also potential targets for nitric oxide (NO)-induced nitrosation. NO, a physiological signaling molecule nitrosates many cellular proteins, causing altered protein and cellular functions.MethodsHere, we have evaluated the roles of NO/NO-derived species in the activity/stability of topo II both in vitro and in human tumor cells, and in the cytotoxicity of topo II-poisons, etoposide and doxorubicin.ResultsTreatment of purified topo IIα with propylamine propylamine nonoate (PPNO), an NO donor, resulted in inhibition of both the catalytic and relaxation activity in vitro, and decreased etoposide-dependent cleavable complex formation in both human HT-29 colon and MCF-7 breast cancer cells. PPNO treatment also induced significant nitrosation of topo IIα protein in these human tumor cells. These events, taken together, caused a significant resistance to etoposide in both cell lines. However, PPNO had no effect on doxorubicin-induced cleavable complex formation, or doxorubicin cytotoxicity in these cell lines.ConclusionInhibition of topo II function by NO/NO-derived species induces significant resistance to etoposide, without affecting doxorubicin cytotoxicity in human tumor cells.General significanceAs tumors express inducible nitric oxide synthase and generate significant amounts of NO, modulation of topo II functions by NO/NO-derived species could render tumors resistant to certain topo II-poisons in the clinic. 相似文献
2.
Pamela T. Bandeira Mara C. Dalmolin Mariana M. de Oliveira Karine C. Nunes Francielle P. Garcia Celso V. Nakamura Alfredo R.M. de Oliveira Leandro Piovan 《Bioorganic & medicinal chemistry》2019,27(2):410-415
The use of antioxidants is the most effective means to protect the organism against cellular damage caused by oxidative stress. In this context, organotellurides have been described as promising antioxidant agents for decades. Herein, a series of N-functionalized organotellurium compounds has been tested as antioxidant and presented remarkable activities by three different in vitro chemical assays. They were able to reduce DPPH radical with IC50 values ranging from 5.08 to 19.20?µg?mL?1, and some of them also reduced ABTS+ radical and TPTZ-Fe3+ complex in ABTS+ and FRAP assays, respectively. Initial structure-activity relationship discloses that the nature of N-substituent strongly influenced both activity and cytotoxicity of the studied compounds. Furthermore, radical scavenging activities of N-functionalized organotellurides have been compared with those of their selenilated congeners, demonstrating that the presence of tellurium atom has an essential role in antioxidant activity. 相似文献
3.
《Bioorganic & medicinal chemistry letters》2019,29(16):2145-2149
Scavenging abilities of animal sera against six reactive species (OH, O2−, RO, t-BuOO, H3C, and 1O2) were determined with the use of multiple free-radical scavenging (MULTIS) method. Commercially available sera from pig, horse, rabbit, Guinea pig, hamster and chicken were subjected to MULTIS analysis and the results were compared with human specimen. In general, animal sera showed lower scavenging ability against OH and RO radicals than human serum. However, it is noteworthy that rabbit and chicken sera have higher scavenging ability against O2− than others. This is consistent with the known data that superoxide dismutase levels in these sera are high. In addition, we determined the uric acid level in animal sera using the uricase-TOOS method. In chicken serum, uric acid was found to be the major effective component in RO scavenging. This paper is first to quantitatively evaluate antioxidant capacities in animal sera. 相似文献
4.
The coupling between neuronal activity and cerebral blood flow (CBF) is essential for normal brain function. The mechanisms behind this neurovascular coupling process remain elusive, mainly because of difficulties in probing dynamically the functional and coordinated interaction between neurons and the vasculature in vivo. Direct and simultaneous measurements of nitric oxide (NO) dynamics and CBF changes in hippocampus in vivo support the notion that during glutamatergic activation nNOS-derived NO induces a time-, space-, and amplitude-coupled increase in the local CBF, later followed by a transient increase in local O2 tension. These events are dependent on the activation of the NMDA-glutamate receptor and nNOS, without a significant contribution of endothelial-derived NO or astrocyte–neuron signaling pathways. Upon diffusion of NO from active neurons, the vascular response encompasses the activation of soluble guanylate cyclase. Hence, in the hippocampus, neurovascular coupling is mediated by nNOS-derived NO via a diffusional connection between active glutamatergic neurons and blood vessels. 相似文献
5.
Physiological processes are often activated by reactive oxygen species (ROS), such as the superoxide anion (O2–) and nitric oxide (NO) produced by cells. We studied the interactions between NO and O2–, and their generators (NO synthase, NOS, and a still elusive oxidase), in human spermatozoa during capacitation (transformations needed for acquisition of fertility). Albumin, fetal cord serum ultrafiltrate, and L-arginine triggered capacitation and ROS generation (NO and O2–) and superoxide dismutase (SOD) and NOS inhibitors prevented all these effects. Surprisingly, capacitation due to exogenous NO (or O2–) was also blocked by SOD (or NOS inhibitors). Probes used were proven specific and innocuous on spermatozoa. Whereas O2– was needed only for 30 min, the continuous NO generation was essential for hours. Capacitation caused a time-dependent increase in protein tyrosine nitration that was prevented by SOD and NOS inhibitors, suggesting that O2– and NO· also act via the formation of ONOO–. Spermatozoa treated with NO (or O2–) initiated a dose-dependent O2– (or NO) production, providing, for the first time in cells, a strong evidence for a two-sided ROS-induced ROS generation. Data presented show a close interaction between NO and O2– and their generators during sperm capacitation. 相似文献
6.
Ana Catarina R. Leite Helena C.F. Oliveira Fabiane L. Utino Rafael Garcia Luciane C. Alberici Mariana P. Fernandes Roger F. Castilho Aníbal E. Vercesi 《BBA》2010,1797(6-7):1210-1216
Mitochondria generated nitric oxide (NO) regulates several cell functions including energy metabolism, cell cycling, and cell death. Here we report that the NO synthase inhibitors (L-NAME, L-NNA and L-NMMA) administered either in vitro or in vivo induce Ca2+-dependent mitochondrial permeability transition (MPT) in rat liver mitochondria via a mechanism independent on changes in the energy state of the organelle. MPT was determined by the occurrence of cyclosporin A sensitive mitochondrial membrane potential disruption followed by mitochondrial swelling and Ca2+ release. In in vitro experiments, the effect of NOS inhibitors was dose-dependent (1 to 50 µM). In addition to cyclosporin A, L-NAME-induced MPT was sensitive to Mg2+ plus ATP, EGTA, and to a lower degree, to catalase and dithiothreitol. In contrast to L-NAME, its isomer D-NAME did not induce MPT. L-NAME-induced MPT was associated with a significant decrease in both the rate of NO generation and the content of mitochondrial S-nitrosothiol. Acute and chronic in vivo treatment with L-NAME also promoted MPT and decreased the content of mitochondrial S-nitrosothiol. SNAP (a NO donor) prevented L-NAME mediated MPT and reversed the decrease in the rate of NO generation and in the content of S-nitrosothiol. We propose that S-nitrosylation of critical membrane protein thiols by NO protects against MPT. 相似文献
7.
《Biochimica et Biophysica Acta (BBA)/General Subjects》2002,1573(2):156-164
The effect of the chemical structure of nitroxyl spin probes on the rate at which ESR signals are lost in the presence of reactive oxygen species (ROS) was examined. When the spin probes were reacted with either hydroxyl radical (OH) or superoxide anion radical (O2−) in the presence of cysteine or NADH, the probes lost ESR signal depending on both their ring structure and substituents. Pyrrolidine nitroxyl probes were relatively resistant to the signal decay caused by O2− with cysteine/NADH. Signal decay rates for these reactions correlated with reported redox potentials of the nitroxyl/oxoammonium couple of spin probes, suggesting that the signal decay mechanism in both cases involves the oxidation of a nitroxyl group. The apparent rate constants of the reactions between the spin probe and OH and between the spin probe and O2− in the presence of cysteine were estimated using mannitol and superoxide dismutase (SOD), respectively, as competitive standards. The rate constants for spin probes and OH were in the order of 109 M−1 s−1, much higher than those for the probes and O2− in the presence of cysteine (103–104 M−1 s−1). These basic data are useful for the measurement of OH and O2− in living animals by in vivo ESR spectroscopy. 相似文献
8.
Binhua Zhou Baojian Li Wei Yi Xianzhang Bu Lin Ma 《Bioorganic & medicinal chemistry letters》2013,23(13):3759-3763
A series of 2-arylbenzimidazole derivatives (3a–3p and 4a–4i) were synthesized and evaluated as potential antioxidant and antimicrobial agents. Their antioxidant properties were evaluated by various in vitro assays including hydroxyl radical (HO) scavenging, superoxide radical anion (O2?) scavenging, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, and ferric reducing antioxidant power. Results demonstrated that compounds with hydroxyl group at the 5-position of benzimidazole ring had a comparable or better antioxidant activity in comparison to standard antioxidant tert-butylhydroquinone (TBHQ). Markedly, compound 4h that showed the highest HO scavenging activity (EC50 = 46 μM) in vitro had a significant reduction of 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced intracellular oxidative stress and H2O2-induced cell death. In addition, these compounds showed moderate to good inhibitory activity against Staphylococcus aureus selectively at noncytotoxic concentrations. 相似文献
9.
In this study, we examined the mechanisms and kinetic profiles of intracellular nitrosative processes using diaminofluorescein (DAF-2) as a target in RAW 264.7 cells. The intracellular formation of the fluorescent, nitrosated product diaminofluorescein triazol (DAFT) from both endogenous and exogenous nitric oxide (NO) was prevented by deoxygenation and by cell membrane-permeable superoxide (O2−) scavengers but not by extracellular bovine Cu,Zn-SOD. In addition, the DAFT formation rate decreased in the presence of cell membrane-permeable Mn porphyrins that are known to scavenge peroxynitrite (ONOO−) but was enhanced by HCO3−/CO2. Together, these results indicate that nitrosative processes in RAW 264.7 cells depend on endogenous intracellular O2− and are stimulated by ONOO−/CO2-derived radical oxidants. The N2O3 scavenger sodium azide (NaN3) only partially attenuated the DAFT formation rate and only with high NO (>120 nM), suggesting that DAFT formation occurs by nitrosation (azide-susceptible DAFT formation) and predominantly by oxidative nitrosylation (azide-resistant DAFT formation). Interestingly, the DAFT formation rate increased linearly with NO concentrations of up to 120–140 nM but thereafter underwent a sharp transition and became insensitive to NO. This behavior indicates the sudden exhaustion of an endogenous cell substrate that reacts rapidly with NO and induces nitrosative processes, consistent with the involvement of intracellular O2−. On the other hand, intracellular DAFT formation stimulated by a fixed flux of xanthine oxidase-derived extracellular O2− that also occurs by nitrosation and oxidative nitrosylation increased, peaked, and then decreased with increasing NO, as previously observed. Thus, our findings complementarily show that intra- and extracellular O2−-dependent nitrosative processes occurring by the same chemical mechanisms do not necessarily depend on NO concentration and exhibit different unusual kinetic profiles with NO dynamics, depending on the biological compartment in which NO and O2− interact. 相似文献
10.
Endothelial dysfunction causes an imbalance in endothelial NO and O2− production rates and increased peroxynitrite formation. Peroxynitrite and its decomposition products cause multiple deleterious effects including tyrosine nitration of proteins, superoxide dismutase (SOD) inactivation, and tissue damage. Studies have shown that peroxynitrite formation during endothelial dysfunction is strongly dependent on the NO and O2− production rates. Previous experimental and modeling studies examining the role of NO and O2− production imbalance on peroxynitrite formation showed different results in biological and synthetic systems. However, there is a lack of quantitative information about the formation and biological relevance of peroxynitrite under oxidative, nitroxidative, and nitrosative stress conditions in the microcirculation. We developed a computational biotransport model to examine the role of endothelial NO and O2− production on the complex biochemical NO and O2− interactions in the microcirculation. We also modeled the effect of variability in SOD expression and activity during oxidative stress. The results showed that peroxynitrite concentration increased with increase in either O2− to NO or NO to O2− production rate ratio (QO2−/QNO or QNO/QO2−, respectively). The peroxynitrite concentrations were similar for both production rate ratios, indicating that peroxynitrite-related nitroxidative and nitrosative stresses may be similar in endothelial dysfunction or inducible NO synthase (iNOS)-induced NO production. The endothelial peroxynitrite concentration increased with increase in both QO2−/QNO and QNO/QO2− ratios at SOD concentrations of 0.1–100 μM. The absence of SOD may not mitigate the extent of peroxynitrite-mediated toxicity, as we predicted an insignificant increase in peroxynitrite levels beyond QO2−/QNO and QNO/QO2− ratios of 1. The results support the experimental observations of biological systems and show that peroxynitrite formation increases with increase in either NO or O2− production, and excess NO production from iNOS or from NO donors during oxidative stress conditions does not reduce the extent of peroxynitrite mediated toxicity. 相似文献
11.
Reactive oxygen species and antioxidant machinery in abiotic stress tolerance in crop plants 总被引:24,自引:0,他引:24
Various abiotic stresses lead to the overproduction of reactive oxygen species (ROS) in plants which are highly reactive and toxic and cause damage to proteins, lipids, carbohydrates and DNA which ultimately results in oxidative stress. The ROS comprises both free radical (O2?, superoxide radicals; OH, hydroxyl radical; HO2, perhydroxy radical and RO, alkoxy radicals) and non-radical (molecular) forms (H2O2, hydrogen peroxide and 1O2, singlet oxygen). In chloroplasts, photosystem I and II (PSI and PSII) are the major sites for the production of 1O2 and O2?. In mitochondria, complex I, ubiquinone and complex III of electron transport chain (ETC) are the major sites for the generation of O2?. The antioxidant defense machinery protects plants against oxidative stress damages. Plants possess very efficient enzymatic (superoxide dismutase, SOD; catalase, CAT; ascorbate peroxidase, APX; glutathione reductase, GR; monodehydroascorbate reductase, MDHAR; dehydroascorbate reductase, DHAR; glutathione peroxidase, GPX; guaicol peroxidase, GOPX and glutathione-S- transferase, GST) and non-enzymatic (ascorbic acid, ASH; glutathione, GSH; phenolic compounds, alkaloids, non-protein amino acids and α-tocopherols) antioxidant defense systems which work in concert to control the cascades of uncontrolled oxidation and protect plant cells from oxidative damage by scavenging of ROS. ROS also influence the expression of a number of genes and therefore control the many processes like growth, cell cycle, programmed cell death (PCD), abiotic stress responses, pathogen defense, systemic signaling and development. In this review, we describe the biochemistry of ROS and their production sites, and ROS scavenging antioxidant defense machinery. 相似文献
12.
Hydroxyl radical (OH) is a radical species highly destructive for lignin during solid-state fermentation (SSF) of straw with Phanerochaete chrysosporium (Pc). The production of OH at different initial Pb2+ concentrations during SSF of straw with Pc was investigated. The results showed that a modest amount (under 200 mg kg−1) of Pb2+ could enhance the production of OH, while a higher Pb2+ concentration resulted in inhibition. The content of OH reached the peak value at day 12 in the whole tested samples, and the maximal content of OH was obtained at initial Pb2+ concentration of 100 mg kg−1. It was also found that the production of OH was connected to enzymatic activity and oxalate content in some degree, in particular, a significant positive correlation was found between oxalate concentration and production of OH.We found that low concentration of Pb2+ can promote the degradation of lignin, and the higher initial Pb2+ concentration (400 mg kg−1) resulted in inhibition. In addition, it appeared that there was no significant correlation between lignin degradation rate and the production of OH when Pb2+ concentration was taken into account. 相似文献
13.
The 1-(secondary amino) diazen-1-ium-1,2-diolates (NONOates) are the most commonly utilized nitric oxide (NO, nitrogen monoxide) donor because of the ability of different NONOates to spontaneously break down liberating NO at different rates, which can be utilized to control NO fluxes. However, the parameters that determine these fluxes of NO generation, half-lives and stoichiometry of NO per donor, can vary significantly with specific experimental conditions in addition to the donor chosen. Here we report straightforward methods that can be used to determine these parameters. For donors of intermediate half-life (10–80 min) a real-time oxymyoglobin (oxyMb) assay can be analyzed to simultaneously determine both the half-life and the total amount of NO liberated, from which the NO flux can be obtained for any given donor concentration. The half-lives obtained by oxyMb assay are very similar to those obtained by following NONOate decomposition kinetics spectrophotometrically, and a survey of several NONOates from different commercial sources show consistent results. These data provide validation for the methodologies employed. In addition, procedures are described for calibration of donors with shorter (<10 min) and longer (>80 min) half-lives. These procedures can be used to reproducibly and routinely calibrate NO fluxes for a variety of donors under any specific condition. 相似文献
14.
In this study, series of novel bromophenol derivatives were synthesized and investigated for their antioxidant and AChE inhibition properties. Novel brominated diarylmethanones were obtained from the acylation reactions of benzoic acids with substituted benzenes. One of the bromodiarylmethanone was synthesized from the bromination of diarylmethanone with molecular bromine. All diarylmethanones were converted into their bromophenol derivatives with BBr3. The antioxidant activities of all synthesized compounds were elucidated by using various bioanalytical assays. Radical scavenging activities of compounds 10–24 were evaluated by means of DPPH and ABTS+ scavenging activities. In addition, reducing ability of 10–24 were determined by Fe3+, Cu2+, and [Fe3+-(TPTZ)2]3 reducing activities. α-Tocopherol, trolox, BHA, and BHT were used as positive antioxidant and radical scavenger molecules. On the other hand, IC50 values were calculated for DPPH, ABTS+ scavenging, and AChE inhibition effects of novel compounds. The results obtained from the current studies clearly show that novel bromophenol derivatives 20–24 have considerable antioxidant, antiradical, and AChE inhibition effects. 相似文献
15.
MicroRNA-506 inhibits the proliferation and invasion of mantle cell lymphoma cells by targeting B7H3
Xiao-wen Zhu Jing Wang Ming-xia Zhu Yan-fang Wang Si-yuan Yang Xiao-yan Ke 《Biochemical and biophysical research communications》2019,508(4):1067-1073
Background
Aberrant expression of B7 homologue 3 (B7H3) has been observed in various malignancies. Our previous study demonstrated that knocking down of B7H3 inhibited cell proliferation, invasion and enhanced the therapeutic efficacy of chemotherapy in mantle cell lymphoma (MCL). However, the mechanism regulating of B7H3 expression remains unknown. Here, we present a new regulatory microRNA of B7H3, miR-506, that directly targets B7H3 and may play an inhibitory role in MCL progression.Methods
The expression of miR-506 and B7H3 was investigated by real-time quantitative PCR (RT-qPCR). B7H3 was confirmed to be a novel direct target gene of miR-506 by a dual-luciferase assay and western blot analysis. MiR-506 overexpression in the Maver and Z138 MCL cell lines was established using lentiviral transduction. Cell counting kit-8, flow cytometry and Transwell assays were used to detect changes in cell proliferation, cycle distribution, migration and invasion, respectively.Results
The RT-qPCR results showed that miR-506 was expressed at a low level, while B7H3 was overexpressed in MCL patients and cell lines. By using a bioinformatics analysis combined with a dual-luciferase assay, we determined that miR-506 could target the 3‘-untranslated region (3′-UTR) of B7H3 mRNA. Moreover, miR-506 had a negative regulatory effect on B7H3 expression according to the western blotting and RT-qPCR results. In terms of function, increased expression of miR-506 led to reduced MCL cell proliferation, invasion and migration, caused cell cycle arrested at G0/G1 phase, similar to the effects of B7H3 knockdown. Furthermore, we measured the expression of invasion-related proteins by western blotting and found that miR-506 could reduce MMP-2 and MMP-9 expression in MCL cells. Rescue experiments suggested that the restoration of B7H3 expression in MCL cells reversed the inhibition of proliferation and invasion induced by miRNA-506 overexpression.Conclusions
Our findings suggest that miR-506 functions as a tumor suppressor miRNA and plays a significant role in inhibiting human MCL cell proliferation and metastasis by suppressing B7H3 expression. 相似文献16.
Sumanta Dey Mithu Guha Athar Alam Manish Goyal Samik Bindu Chinmay Pal Pallab Maity Kalyan Mitra Uday Bandyopadhyay 《Free radical biology & medicine》2009,46(2):271-281
Activation of the mitochondrial apoptosis pathway by oxidative stress has been implicated in hepatocyte apoptosis during malaria. Because mitochondria are the source and target of reactive oxygen species (ROS), we have investigated whether hepatocyte apoptosis is linked to mitochondrial pathology and mitochondrial ROS generation during malaria. Malarial infection induces mitochondrial pathology by inhibiting mitochondrial respiration, dehydrogenases, and transmembrane potential and damaging the ultrastructure as evident from transmission electron microscopic studies. Mitochondrial GSH depletion and formation of protein carbonyl indicate that mitochondrial pathology is associated with mitochondrial oxidative stress. Fluorescence imaging of hepatocytes documents intramitochondrial superoxide anion (O2?) generation during malaria. O2? inactivates mitochondrial aconitase to release iron from iron–sulfur clusters, which forms the hydroxyl radical (OH) interacting with H2O2 produced concurrently. Malarial infection inactivates mitochondrial aconitase, and carbonylation of aconitase is evident from Western immunoblotting. The release of iron has been documented by fluorescence imaging of hepatocytes using Phen Green SK, and mitochondrial OH generation has been confirmed. During malaria, the depletion of cardiolipin and formation of the mitochondrial permeability transition pore favor cytochrome c release to activate caspase-9. Interestingly, mitochondrial OH generation correlates with the activation of both caspase-9 and caspase-3 with the progress of malarial infection, indicating the critical role of OH. 相似文献
17.
Ultraviolet B light (UVB) activates nitric oxide synthase(s) (NOSs) and nitric oxide (NO) production, which plays a role in regulation of apoptosis. However, the role of NO in UVB-induced apoptosis remains controversial. In this study, we analyzed expression and activation of constitutive NOSs (cNOSs) and their roles in UV-induced apoptosis of HaCaT keratinocytes. Our data showed that the expression of neuronal NOS (nNOS) was increased while endothelial NOS (eNOS) was uncoupled in the early phase (0–6 h) post-UVB. The expression of both cNOSs peaked at 12 h post-UVB and NO was transiently elevated with 30 min and then steadily rose from 6 to 18 h post-UVB. The expression of iNOS was detected at 6 h post-UVB and then sturdily increased. Inhibition of cNOSs with l-NAME reduced the inducibility of NO in the early and late phases of irradiation. Along with the eNOS uncoupling, an increased level of peroxynitrite (ONOO?) was detected in the early phase, but not in the late phase post-UVB. Inhibition of cNOSs reduced the production of ONOO? in the early time, but led to an increase of ONOO? in the late time after UVB-irradiation. The results indicate that cNOSs regulate NO/ONOO? imbalance after UVB-irradiation. Our data suggested that the activation of cNOSs in the early phase post-UVB leads to NO/ONOO? imbalance and promotes apoptosis via a caspase 3-independent pathway. The elevation of NO in the late phase of UVB-irradiation is mainly produced by inducible NOS (iNOS). However, cNOSs also contribute to the NO production and to maintain a higher NO/ONOO? ratio, which reduces caspase 3 activity and protects cells from UVB-induced apoptosis. 相似文献
18.
Gorka San José Julen Bidegain Pablo A. Robador Javier Díez Ana Fortuño Guillermo Zalba 《Free radical biology & medicine》2009,46(8):1058-1067
Insulin stimulates superoxide (O2?) production in monocytes and macrophages. However, the mechanisms through which insulin induces O2? production are not completely understood. In this study, we (a) characterized the enzyme and the pathways involved in insulin-stimulated O2? production in human monocytes and murine macrophages, and (b) analyzed the consequences of insulin-stimulated O2? production on the cellular phenotype in these cells. We showed that insulin stimulated O2? production, and promoted p47phox translocation to the plasma membrane. Insulin-induced O2? production and p47phox translocation were prevented in the presence of specific inhibitors of PI3K and PKC. Insulin-mediated NADPH oxidase activation stimulated MMP-9 activation in monocytes and cell proliferation in macrophages. The effect of insulin on these phenotypic responses was mediated through NFκB, p38MAPK, and ERK 1/2 activation. Small-interfering RNA-specific gene silencing targeted specifically against Nox2 reduced the cognate protein expression, decreased insulin-induced O2? production, inhibited the turn on of NFκB, p38MAPK, and ERK 1/2, and reduced cell proliferation in macrophages. These findings suggest a pivotal role for NADPH oxidase in insulin-induced proliferation and proteolytic activation in monocytes and macrophages, respectively, and identify a pathway that may play a pathological role in hyperinsulinemic states. 相似文献
19.
Rosemari Otton Douglas Popp Marin Anaysa Paola Bolin Rita de Cássia Macedo dos Santos Tatiana Geraldo Polotow Sandra Coccuzzo Sampaio Marcelo Paes de Barros 《Chemico-biological interactions》2010,186(3):306-315
Diabetes mellitus is a syndrome of impaired insulin secretion/sensitivity and frequently diagnosed by hyperglycemia, lipid abnormalities, and vascular complications. The diabetic ‘glucolipotoxicity’ also induces immunodepression in patients by redox impairment of immune cells. Astaxanthin (ASTA) is a pinkish-orange carotenoid found in many marine foods (e.g. shrimp, crabs, salmon), which has powerful antioxidant, photoprotective, antitumor, and cardioprotective properties. Aiming for an antioxidant therapy against diabetic immunodepression, we here tested the ability of prophylactic ASTA supplementation (30 days, 20 mg ASTA/kg BW) to oppose the redox impairment observed in isolated lymphocytes from alloxan-induced diabetic Wistar rats. The redox status of lymphocytes were thoroughly screened by measuring: (i) production of superoxide (O2?), nitric oxide (NO), and hydrogen peroxide (H2O2); (ii) cytosolic Ca2+; (iii) indexes of oxidative injury; and (iv) activities of major antioxidant enzymes. Hypolipidemic and antioxidant effects of ASTA in plasma of ASTA-fed/diabetic rats were apparently reflected in the circulating lymphocytes, since lower activities of catalase, restored ratio between glutathione peroxidase and glutathione reductase activities and lower scores of lipid oxidation were concomitantly measured in those immune cells. Noteworthy, lower production of NO and O2? (precursors of peroxynitrite), and lower cytosolic Ca2+ indicate a hypothetical antiapoptotic effect of ASTA in diabetic lymphocytes. However, questions are still open regarding the proper ASTA supplementation dose needed to balance efficient antioxidant protection and essential NO/H2O2-mediated proliferative capacities of diabetic lymphocytes. 相似文献
20.
Recently, D.J. Hall et al. reported that ethidium (E+) is formed as a major product of hydroethidine (HE) or dihydroethidium reaction with superoxide (O2−) in intact animals with low tissue oxygen levels (J. Cereb. Blood Flow Metab. 32:23–32, 2012). The authors concluded that measurement of E+ is an indicator of O2− formation in intact brains of animals. This finding is in stark contrast to previous reports using in vitro systems showing that 2-hydroxyethidium, not ethidium, is formed from the reaction between O2− and HE. Published in vivo results support the in vitro findings. In this study, we performed additional experiments in which HE oxidation products were monitored under different fluxes of O2−. Results from these experiments further reaffirm our earlier findings (H. Zhao et al., Free Radic. Biol. Med. 34:1359, 2003). We conclude that whether in vitro or in vivo, E+ measured by HPLC or by fluorescence lifetime imaging is not a diagnostic marker product for O2− reaction with HE. 相似文献