In vitro Activation of heme oxygenase-2 by menadione and its analogs

Vukomanovic, Dragic; Rahman, Mona N.; Bilokin, Yaroslav V.; Golub, Andriy G.; Brien, James F.; Szarek, Walter A.; Jia, Zongchao; Nakatsu, Kanji

doi:10.1186/2045-9912-4-4

Cited by 12 publications

(19 citation statements)

References 17 publications

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“…In these experiments, the baseline activity represents HO activity. Within the naphthoquinone family, we found that many members acted similarly to MD by increasing CO formation while some others did not; our results of testing ~50 other naphthoquinones were reported earlier 6. The presence of a variety of chemical entities increased CO production many-fold; for example, OT-7116980337 (Otava, Toronto, Canada), SI-1606 (Sniekus Innovations, Kingston, Canada) and VV-101 (St. Sava Bioanalytical & Medical Research, Kingston, Canada) ( Table 1 ).…”

Section: Resultssupporting

confidence: 82%

“…This was the case of MD analogs such as the 2,4-dimethoxy-2-methylnaphthoquinone and 2,5,6,7,8-pentafluoro-3-methyl-1,4-naphthalenedione; in the former, quinone oxygens that are essential for redox function have been replaced by methoxy groups, and the fluorines of pentafluora analog would interfere with electron flow by virtue of their high electron affinity. Neither of these compounds resulted in an increase in CO production 6. Similarly our observation that SI-441 did not increase CO production may be attributed to preventing redox cycling; this could be due the inductive effect of the electronegative Br atom and electron delocalization of the tautomeric forms via intramolecular hydrogen bonding involving the H of the –OH and the carbonyl group as discussed in the review by Brunmark and Cadenas 20.…”

Section: Discussionsupporting

confidence: 57%

“…In the course of screening molecular skeletons for candidates as novel HO inhibitors, we observed that menadione (MD) and some other drugs enhanced the production of CO by incubation mixtures containing rat brain microsomes, as a source of HO-2. This was interpreted to represent the activation of HO-2 as described earlier 56…”

Section: Introductionmentioning

confidence: 98%

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Drug-enhanced carbon monoxide production from heme by cytochrome P450 reductase

et al. 2017

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Carbon monoxide (CO) formed endogenously is considered to be cytoprotective, and the vast majority of CO formation is attributed to the degradation of heme by heme oxygenases-1 and -2 (HO-1, HO-2). Previously, we observed that brain microsomes containing HO-2 produced many-fold more CO in the presence of menadione and its congeners; herein we explored these observations further. We determined the effects of various drugs on CO production of rat brain microsomes and recombinant human cytochrome P450 reductase (CPR); CO was measured by gas chromatography with reductive detection. Brain microsomes of Sprague-Dawley rats or recombinant human cytochrome P450 reductase (CPR) were incubated with NADPH and various drugs in closed vials in phosphate buffer at pH 7.4 and 37°C. After 15 minutes, the reaction was stopped by cooling in dry ice, and the headspace gas was analyzed for CO production using gas chromatography with reductive (mercuric oxide) detection. We observed drug-enhanced CO production in the presence of both microsomes and recombinant CPR alone; the presence of HO was not required. A range of structurally diverse drugs were capable of amplifying this CO formation; these molecules had structures consistent with redox cycling capability. The addition of catalase to a reaction mixture, that contained activating drugs, inhibited the production of CO. Drug-enhanced CO formation can be catalyzed by CPR. The mechanism of CPR activation was not through classical drug-receptor mediation. Redox cycling may be involved in the drug-induced amplification of CO production by CPR through the production of reactive oxygen species.

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Section: Resultssupporting

confidence: 82%

Section: Discussionsupporting

confidence: 57%

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Drug-enhanced carbon monoxide production from heme by cytochrome P450 reductase

et al. 2017

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“…The HO-2 isoform is considered to be constitutively expressed, but expression can change in response to certain stimuli (hypoxia, glucocorticoids) (Han et al 2005;He et al 2010;Vukomanovic et al 2011;Zhang et al 2006). In contrast to HO-1 expression in the brain, HO-2 is the predominant isoform expressed in neurons.…”

Section: Ho-1 Expression In Multiple Brain Regions Associates With Csmentioning

confidence: 99%

Neuroinflammation associates with antioxidant heme oxygenase-1 response throughout the brain in persons living with HIV

et al. 2020

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Previous studies showed that persons living with HIV (PLWH) demonstrate higher brain prefrontal cortex neuroinflammation and immunoproteasome expression compared to HIV-negative individuals; these associate positively with HIV levels. Lower expression of the antioxidant enzyme heme oxygenase 1 (HO-1) was observed in PLWH with HIV-associated neurocognitive impairment (HIV-NCI) compared to neurocognitively normal PLWH. We hypothesized that similar expression patterns occur throughout cortical, subcortical, and brainstem regions in PLWH, and that neuroinflammation and immunoproteasome expression associate with lower expression of neuronal markers. We analyzed autopsied brains (15 regions) from 9 PLWH without HIV-NCI and 7 matched HIV-negative individuals. Using Western blot and RT-qPCR, we quantified synaptic, inflammatory, immunoproteasome, endothelial, and antioxidant biomarkers, including HO-1 and its isoform heme oxygenase 2 (HO-2). In these PLWH without HIV-NCI, we observed higher expression of neuroinflammatory, endothelial, and immunoproteasome markers in multiple cortical and subcortical regions compared to HIV-negative individuals, suggesting a global brain inflammatory response to HIV. Several regions, including posterior cingulate cortex, globus pallidus, and cerebellum, showed a distinct pattern of higher type I interferon (IFN)-stimulated gene and immunoproteasome expression. PLWH without HIV-NCI also had (i) stable or higher HO-1 expression and positive associations between (ii) HO-1 and HIV levels (CSF, plasma) and (iii) HO-1 expression and neuroinflammation, in multiple cortical, subcortical, and brainstem regions. We observed no differences in synaptic marker expression, suggesting little, if any, associated neuronal injury. We speculate that this may reflect a neuroprotective effect of a concurrent HO-1 antioxidant response despite global neuroinflammation, which will require further investigation.

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“…Вікасол здебільшого використовується як токсикант у моделюванні оксидаційного стресу [11,33]. За останні роки дослідження фармакологічних властивостей хінонів значно активізувались [3,8,11,13,24,31], хоча їх вплив на жирнокислотний склад тканин вивчено не достатньо. Описано вплив вікасолу на процеси транскрипції та активації чинників, які задіяні у ланцюгу антиоксидантної відповіді клітини.…”

Section: біохіміяunclassified

Жирнокислотний Склад Міокарду Гусей За Дії Вікасолу

Яковійчук¹,

Данченко²,

Danchenko³

et al. 2019

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In science vicasol is known to be relative to the energy and antioxidant systems of tissues closely related to the biosynthesis and oxidation of fatty acids. This effect may cause changes in the fatty acid composition of tissues, and numerous works on the positive effect of quinones and their derivatives on the myocardial function, suggest that the proper dose and feeding can increase the stability and productivity of poultry. The given was aims to study the effect of vicasol on the fatty acid composition of goose myocardium. Myocardium was chosen as a biological object. Biological material was collected every 7 days throughout the period from the 21st to the 35th day of ontogeny, characterized by the state of physiological tension of geese. Feeding of geese with vicasol at a dose of 0.7 mg / kg body weight began with the 3rd day of ontogeny. Fatty acid analysis in myocardial tissues was performed by gas-liquid chromatography, pre-fabric samples were processed with the method by Palmer (1971) to obtain tissue lipid extracts. According to the results of the study, due to various changes in the content of the entire spectrum of fatty acids of the tissue during the experiment - the use of vicasol causes a slight increase in the unsaturation and the total content of unsaturated fatty acids in the myocardium of geese. These fluctuations are realized depending on the physiological state of the body. where vicasol can stimulate both the biosynthesis processes of individual fatty acids and their mitochondrial and microsomal oxidation, as evidenced by multidirectional reliable changes in the content of their entire spectrum. In particular, on the 21st day, the content of docosopentaenoic acid increased by 36.3% whereas the content of docosohexaenoic and linolenic acids decreased by an average of 21–24%, on the 28th day the content of eicosatetraic and docosahexaenoic acids increased whereas the content of the linoleic acids dropped by 22.6% in control groups. On the 35th day, the content of basic unsaturated fatty acids: palmitooleic, linoleic, linolenic and docosohexaenoic acids increased in the tissue under the influence of vicasol with complete depletion of docosopentaenoic acid. These fluctuations in fatty acid composition cause a slight increase in the total content of unsaturated fatty acids and increase the unsaturation of myocardial lipids on the 28th and 35th days of ontogeny of geese. Based on previous results regarding the antioxidant state of myocardium affected by vicasol and the given findings, which prove changes in the content of the entire spectrum of fatty acids during the selected ontogeny, vicasol can be used in poultry farming as a tool to improve the quality and the resilience of poultry.

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In vitro Activation of heme oxygenase-2 by menadione and its analogs

Cited by 12 publications

References 17 publications

Drug-enhanced carbon monoxide production from heme by cytochrome P450 reductase

Drug-enhanced carbon monoxide production from heme by cytochrome P450 reductase

Neuroinflammation associates with antioxidant heme oxygenase-1 response throughout the brain in persons living with HIV

Жирнокислотний Склад Міокарду Гусей За Дії Вікасолу

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