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21.
Nina Kaludercic Andrea CarpiRoberta Menabò Fabio Di Lisa Nazareno Paolocci 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2011,1813(7):1323-1332
Recent evidence highlights monoamine oxidases (MAO) as another prominent source of oxidative stress. MAO are a class of enzymes located in the outer mitochondrial membrane, deputed to the oxidative breakdown of key neurotransmitters such as norepinephrine, epinephrine and dopamine, and in the process generate H2O2. All these monoamines are endowed with potent modulatory effects on myocardial function. Thus, when the heart is subjected to chronic neuro-hormonal and/or peripheral hemodynamic stress, the abundance of circulating/tissue monoamines can make MAO-derived H2O2 production particularly prominent. This is the case of acute cardiac damage due to ischemia/reperfusion injury or, on a more chronic stand, of the transition from compensated hypertrophy to overt ventricular dilation/pump failure. Here, we will first briefly discuss mitochondrial status and contribution to acute and chronic cardiac disorders. We will illustrate possible mechanisms by which MAO activity affects cardiac biology and function, along with a discussion as to their role as a prominent source of reactive oxygen species. Finally, we will speculate on why MAO inhibition might have a therapeutic value for treating cardiac affections of ischemic and non-ischemic origin. This article is part of a Special Issue entitled: Mitochondria and Cardioprotection. 相似文献
22.
Jason L. Wedding Barry Lai Stefan Vogt Hugh H. Harris 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(11):2393-2404
Background
A variety of selenium compounds have been observed to provide protection against oxidative stress, presumably by mimicking the mechanism of action of the glutathione peroxidases. However, the selenium chemistry that underpins the action of these compounds has not been unequivocally established.Methods
The synchrotron based techniques, X-ray absorption spectroscopy and X-ray fluorescence microscopy were used to examine the cellular speciation and distribution of selenium in SH-SY5Y cells pretreated with one of two diphenyl diselenides, or ebselen, followed by peroxide insult.Results
Bis(2-aminophenyl)diselenide was shown to protect against oxidative stress conditions which mimic ischemic strokes, while its nitro analogue, bis(2-nitrophenyl)diselenide did not. This protective activity was tentatively assigned to the reductive cleavage of bis(2-aminophenyl)diselenide inside human neurocarcinoma cells, SH-SY5Y, while bis(2-nitrophenyl)diselenide remained largely unchanged. The distinct chemistries of the related compounds were traced by the changes in selenium speciation in bulk pellets of treated SH-SY5Y cells detected by X-ray absorption spectroscopy. Further, bis(2-aminophenyl)diselenide, like the known stroke mitigation agent ebselen, was observed by X-ray fluorescence imaging to penetrate into the nucleus of SH-SY5Y cells while bis(2-nitrophenyl)diselenide was observed to be excluded from the nuclear region.Conclusions
The differences in activity were thus attributed to the varied speciation and cellular localisation of the compounds, or their metabolites, as detected by X-ray absorption spectroscopy and X-ray fluorescence microscopy.Significance
The work is significant as it links, for the first time, the protective action of selenium compounds against redox stress with particular chemical speciation using a direct measurement approach. 相似文献23.
24.
Ryan J. Mailloux Jian Ying Xuan Brittany Beauchamp Linda Jui Marjorie Lou Mary-Ellen Harper 《The Journal of biological chemistry》2013,288(12):8365-8379
Glutathionylation has emerged as a key modification required for controlling protein function in response to changes in cell redox status. Recently, we showed that the glutathionylation state of uncoupling protein-3 (UCP3) modulates the leak of protons back into the mitochondrial matrix, thus controlling reactive oxygen species production. However, whether or not UCP3 glutathionylation is mediated enzymatically has remained unknown because previous work relied on the use of pharmacological agents, such as diamide, to alter the UCP3 glutathionylation state. Here, we demonstrate that glutaredoxin-2 (Grx2), a matrix oxidoreductase, is required to glutathionylate and inhibit UCP3. Analysis of bioenergetics in skeletal muscle mitochondria revealed that knock-out of Grx2 (Grx2−/−) increased proton leak in a UCP3-dependent manner. These effects were reversed using diamide, a glutathionylation catalyst. Importantly, the increased leak did not compromise coupled respiration. Knockdown of Grx2 augmented proton leak-dependent respiration in primary myotubes from wild type mice, an effect that was absent in UCP3−/− cells. These results confirm that Grx2 deactivates UCP3 by glutathionylation. To our knowledge, this is the first enzyme identified to regulate UCP3 by glutathionylation and is the first study on the role of Grx2 in the regulation of energy metabolism. 相似文献
25.
Chronic myeloid leukemia (CML) is a lethal malignancy, and the progress toward long‐term survival has stagnated in recent decades. Pristimerin, a quinone methide triterpenoid isolated from the Celastraceae and Hippocrateaceae families, is well‐known to exert potential anticancer activities. In this study, we investigated the effects and the mechanisms of action on CML. We found that pristimerin inhibited cell proliferation of K562 CML cells by causing G1 phase arrest. Furthermore, we demonstrated that pristimerin triggered autophagy and apoptosis. Intriguingly, pristimerin‐induced cell death was restored by an autophagy inhibitor, suggesting that autophagy is cross‐linked with pristimerin‐induced apoptosis. Further studies revealed that pristimerin could produce excessive reactive oxygen species (ROS), which then induce JNK activation. These findings provide clear evidence that pristimerin might be clinical benefit to patients with CML. 相似文献
26.
目的:利用逆转录病毒载体pBaba-puro构建携带ROS1基因及其CD74-ROS1融合基因的重组载体pBaba-puro-ROS1,pBaba-puro-CD74-ROS1。方法:设计与合成引物,提取组织标本RNA,反转录和PCR扩增,经BamHI和TaqI双酶切,琼脂糖凝胶电泳,切胶回收进行连接转化,并再次酶切鉴定,测序分析。结果:成功构建携带ROS1基因及其CD74-ROS1融合基因的重组载体pBaba-puro-ROS1,pBaba-puro-CD74-ROS1,并通过双酶切与测序鉴定。结论:利用逆转录病毒载体基因重组技术能够成功构建出携带相应基因的逆转录病毒,可用于后续研究。 相似文献
27.
Subash Chandra Gupta Hifzur Rahman Siddique Neeraj Mathur Achchhe Lal Vishwakarma Ranjit Kishore Mishra Daya Krishna Saxena Debapratim Kar Chowdhuri 《Biochimica et Biophysica Acta (BBA)/General Subjects》2007
We examined a hypothesis that reactive oxygen species (ROS) generated by organophosphate compound dichlorvos modulates Hsp70 expression and anti-oxidant defense enzymes and acts as a signaling molecule for apoptosis in the exposed organism. Dichlorvos (0.015–15.0 ppb) without or with inhibitors of Hsp70, superoxide dismutase (SOD) and catalase (CAT) were fed to the third instar larvae of Drosophila melanogaster transgenic for hsp70 (hsp70-lacZ) Bg9 to examine Hsp70 expression, oxidative stress and apoptotic markers. A concentration- and time-dependent significant increase in ROS generation accompanied by a significant upregulation of Hsp70 preceded changes in antioxidant defense enzyme activities and contents of glutathione, malondialdehyde and protein carbonyl in the treated organisms. An inhibitory effect on SOD and CAT activities significantly upregulated ROS generation and Hsp70 expression in the exposed organism while inhibition of Hsp70 significantly affected oxidative stress markers induced by the test chemical. A comparison made among ROS generation, Hsp70 expression and apoptotic markers showed that ROS generation is positively correlated with Hsp70 expression and apoptotic cell death end points indicating involvement of ROS in the overall adversity caused by the test chemical to the organism. The study suggests that (a) Hsp70 and anti-oxidant enzymes work together for cellular defense against xenobiotic hazard in D. melanogaster and (b) free radicals may modulate Hsp70 expression and apoptosis in the exposed organism. 相似文献
28.
Scavenging of reactive oxygen species by a novel glucurinated flavonoid antioxidant isolated and purified from spinach 总被引:4,自引:0,他引:4
NAO is a natural water soluble antioxidant that was isolated and purified from spinach leaves. Using HPLC, NMR, and CMR spectroscopy, the main components were identified as flavonoids and p-coumaric acid derivatives. The NAO was found to be a very effective antioxidant in several in vivo and in vitro biological systems. In the present study, the antioxidant activity of the novel antioxidant glucurinated flavonoid (GF) isolated and characterized from NAO, is compared to well-known antioxidants. In addition, the direct free radical scavenging properties of the purified component GF were studied using the electron spin resonance (ESR) technique. GF and NAO were found to be superior to EGCG and NAC and to the Vitamin E homologue Trolox in inhibiting reactive oxygen species (ROS) formation in the autooxidation system of linoleic acid and in fibroblasts exposed to metal oxidation. GF and NAO were found to inhibit the ESR signal intensity of DMPO-O(2) radical formation during the riboflavin photodynamic reaction. 10 mM GF caused approximately 90% inhibition in the intensity of the ESR signal, while NAO at a concentration of 60 microg/ml caused an inhibition of about 50%. Using the Fenton reaction, GF and NAO were found to inhibit DMPO-OH radical formation. A concentration of 2 mM GF caused a 70% inhibition in the intensity of the DMPO-OH radical ESR signal, while propyl gallate at the same concentration caused only 50% inhibition. Furthermore, both GF and NAO also inhibited the (1)O(2) dependent TEMPO radical generated in the photoradiation TPPS4 system. About 80% inhibition was obtained by 4 mM GF. The results obtained indicate that the natural antioxidants derived from spinach may directly affect the scavenging of ROS and, as a consequence, may be considered as effective sources for combating oxidative damage. 相似文献
29.
Although increasing evidence shows the nutritional benefits of calcium fructoborate (CF) on animals and humans, its action
mechanism has not been clearly identified. The present study aims to investigate the possible antioxidant function of CF.
Based on its efficiency in skin wound healing, the authors tested whether CF possesses antioxidant properties on human keratinocytes
cultures, in a complete serum-free medium (KMK-2; Sigma). The cells treated with CF (0–450 nmol/culture medium) were exposed
to exogenous 100 μmol of hydrogen peroxide to mimic the oxidative stress. The changes in general cell oxidant production evaluated
with dihydrorhodamine-123 showed that the intracellular reactive oxygen species (ROS) were markedly reduced by preincubation
with CF. The maximum antioxidant activity was notice at 90 nmol CF. To assess the reactivity of CF on ROS, we analyzed its
ability to inhibit the superoxide-dependent auto-oxidation of pyrogallol. The CF inhibited the pyrogallol auto-oxidation depending
on time and concentration, which suggests its possible role as a superoxide radical scavenger. Taken together, our results
indicate that CF has antioxidant activity, which could have clinical significance in protecting cells from oxidant-induced
injury. A hypothetic mechanism for the antioxidant activity of CF is proposed. 相似文献
30.
Zinc pyrithione salvages reperfusion injury by inhibiting NADPH oxidase activation in cardiomyocytes
Kasi V Bodiga S Kommuguri UN Sankuru S Bodiga VL 《Biochemical and biophysical research communications》2011,(2):270-275
Zinc pyrithione (ZPT), has a strong anti-apoptotic effect when administered just before reperfusion. Because oxidative stress has been proposed to contribute to myocardial reperfusion injury, we tested whether ZPT can reduce the production of reactive oxygen species during reoxygenation in cultured neonatal rat cardiac myocytes and evaluated the role of NADPH oxidase in hypoxia/reoxygenation (H/R) injury. The cells were subjected to 8 h of simulated ischemia, followed by either 30 min or 16 h of reoxygenation. ZPT when started just before reoxygenation significantly reduced superoxide generation, LDH release and improved cell survival compared to H/R. Attenuation of the ROS production by ZPT paralleled its capacity to prevent pyknotic nuclei formation. In addition, ZPT reversed the H/R-induced expression of NOX2 and p47phox phosphorylation indicating that ZPT directly protects cardiomyocytes from reperfusion injury by a mechanism that attenuates NADPH oxidase mediated intracellular oxidative stress. 相似文献