Hydrogen peroxide, nitric oxide and ATP are molecules involved in cardiac mitochondrial biogenesis in Diabetes

Bombicino, Silvina Sonia; Iglesias, Darío E.; Rukavina-Mikusic, Ivana A.; Buchholz, Bruno; Gelpi, Ricardo J.; Boveris, Alberto; Valdez, Laura B.

doi:10.1016/j.freeradbiomed.2017.07.027

Cited by 26 publications

(17 citation statements)

References 81 publications

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“…In particular, macrophages stimulated by inflammatory stimuli produce pro-inflammatory factors, such as cytokines and nitric oxide (NO) [ 3 ]. NO has a critical role in many diseases, including diabetes, rheumatoid arthritis, and atherosclerosis [ 4 , 5 , 6 ]. NO is produced by inducible NO synthase (iNOS) in macrophages under various inflammatory conditions that is up-regulated by inflammatory stimuli including lipopolysaccharide (LPS), and it can lead to excessive NO production by activated macrophages [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo

et al. 2017

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The ocean is a rich resource of flora, fauna, food, and biological products. We found a wild-type bacterial strain, Pseudoalteromonas sp. M2, from marine water and isolated various secondary metabolites. Pseudane-VII is a compound isolated from the Pseudoalteromonas sp. M2 metabolite that possesses anti-melanogenic activity. Inflammation is a response of the innate immune system to microbial infections. Macrophages have a critical role in fighting microbial infections and inflammation. Recent studies reported that various compounds derived from natural products can regulate immune responses including inflammation. However, the anti-inflammatory effects and mechanism of pseudane-VII in macrophages are still unknown. In this study, we investigated the anti-inflammatory effects of pseudane-VII. In present study, lipopolysaccharide (LPS)-induced nitric oxide (NO) production was significantly decreased by pseudane-VII treatment at 6 μM. Moreover, pseudane-VII treatment dose-dependently reduced mRNA levels of pro-inflammatory cytokines including inos, cox-2, il-1β, tnf-α, and il-6 in LPS-stimulated macrophages. Pseudane-VII also diminished iNOS protein levels and IL-1β secretion. In addition, Pseudane-VII elicited anti-inflammatory effects by inhibiting ERK, JNK, p38, and nuclear factor (NF)-κB-p65 phosphorylation. Consistently, pseudane-VII was also shown to inhibit the LPS-stimulated release of IL-1β and expression of iNOS in mice. These results suggest that pseudane-VII exerted anti-inflammatory effects on LPS-stimulated macrophage activation via inhibition of ERK, JNK, p38 MAPK phosphorylation, and pro-inflammatory gene expression. These findings may provide new approaches in the effort to develop anti-inflammatory therapeutics.

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Section: Introductionmentioning

confidence: 99%

Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo

et al. 2017

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“…20 These enzymes are responsible of producing NO in the heart, being essential for heart homeostasis and mechanical activity. 21 The enhancement in NO production could be associated with nitration of cytoskeletal proteins, leading to alterations in cardiac contractility. 22 In diabetic hearts, the NOS activity inhibition by L-NMMA or L-NAME, improves cardiac activity, suggesting that both NO and peroxynitrite (ONOO -) could be associated with the inhibition of cardiac contractility.…”

Section: Discussionmentioning

confidence: 99%

Moringa oleifera leaves extract regulate the activity of nitric oxide synthases and paraoxonase 1 in diabetic rat

Sierra-Campos¹

2018

MOJBOC

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This study was aimed at evaluating the effects of M. oleifera leaves extract on biochemical physiological parameters, nitric oxide synthase and paraoxonase 1 activities of diabetic model rats. Eighteen Wistar rats were equally split into three groups as follow: control (water), alloxan administration (120 mg/kg b.w), and M. oleifera extract treatment (200 mg/kg b.w., daily for twenty-one days), with six rats per group. Glucose, triglycerides, glycated hemoglobin, advanced end products, nitrites were measured in serum. In parallel, nitric oxide synthase (NOS) and paraoxonase 1 (PON1) activities were tested in heart. The results showed that alloxan induces alterations in nitric oxide homeostasis and inhibited the activities of constitutive NOS and PON1, resulting in oxidative stress. While the levels of AGEs and HbA 1c were elevated in the serum of alloxan-diabetic animals. Oral administration of M. oleifera in diabetic animals reduced the glucose, triglycerides, AGEs and HbA1c. In addition, M. oleifera treatment significantly rescued the cNOS and PON1 compared to nontreated diabetic group. Surprisingly, we observed a significantly activation of PON1 activity in the M. oleifera treatment compared to control group. However, are necessary to further elucidate the activation mechanism. These findings provide a perspective on the cardioprotective effects of diabetic conditions.

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“…Results from our laboratory have shown that even in physiopathological situations in which NO production is reduced, mitochondrial ONOOproduction rate may be slightly increased if the steady-state concentration of O 2 is augmented, with the consequent oxidation of biomolecules or modification of proteins by nitration. 61,65 We have observed that in myocardial stunning 61,65 and in streptozotocin (STZ)-induced diabetes, 62,39 the cardiac mitochondrial dysfunction implied the reduction in state 3 O 2 consumption sustained by glutamate-malate, the decrease in mitochondrial Complex I-III activity, and the enhancement in H 2 O 2 production rate (Table 1), among others. However, while in the mitochondrial dysfunction produced as a consequence of hyperglycemia, an increase in NO production rate (23%) and in mtNOS expression (132%) 39 were observed together with a reduction (50%) in Mn-SOD activity, in the mitochondrial impairment that accompanied the initial phase of stunned heart (15 min of ischemia and 30 min of reperfusion), a reduction in NO production rate (28%), without changes in mtNOS expression and SOD activity 61 were detected, as expected for an acute stress model.…”

Section: Kinetic Control Of Onoo-production In Mitochondriamentioning

confidence: 99%

“…30,31 In addition, mtNOS expression and activity are positively regulated in inflammatory processes 32,33 and positively or negatively modulated by pharmacological situations, 34 such as haloperidol, 35 chlorpromazine 36 and enalapril treatments. 37 Moreover, changes in mtNOS activity and expression have been associated to the role of NO as signaling molecule involved in mitochondrial biogenesis, 38,39 understood as de novo formation of mitochondria during the cellular life cycle. In turn, the product of mtNOS activity, i.e.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial peroxynitrite generation is mainly driven by superoxide steady-state concentration rather than by nitric oxide steady-state concentration

Valdez

Bombicino

Iglesias

et al. 2018

IJMBOA

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Hydrogen peroxide, nitric oxide and ATP are molecules involved in cardiac mitochondrial biogenesis in Diabetes

Cited by 26 publications

References 81 publications

Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo

Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo

Moringa oleifera leaves extract regulate the activity of nitric oxide synthases and paraoxonase 1 in diabetic rat

Mitochondrial peroxynitrite generation is mainly driven by superoxide steady-state concentration rather than by nitric oxide steady-state concentration

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