scholarly journals Attenuation of Ca2+ homeostasis, oxidative stress, and mitochondrial dysfunctions in diabetic rat heart: insulin therapy or aerobic exercise?

2015 ◽  
Vol 119 (2) ◽  
pp. 148-156 ◽  
Author(s):  
Márcia F. da Silva ◽  
Antônio J. Natali ◽  
Edson da Silva ◽  
Gilton J. Gomes ◽  
Bruno G. Teodoro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Therapy ◽  
Diabetic Rat ◽  
Swimming Training ◽  
Mitochondrial Dysfunctions ◽  
Mptp Opening ◽  
Rat Hearts ◽  
Mitochondrial Functions ◽  
Insulin Replacement ◽  
And Mitochondrial Functions

We tested the effects of swimming training and insulin therapy, either alone or in combination, on the intracellular calcium ([Ca2+]i) homeostasis, oxidative stress, and mitochondrial functions in diabetic rat hearts. Male Wistar rats were separated into control, diabetic, or diabetic plus insulin groups. Type 1 diabetes mellitus was induced by streptozotocin (STZ). Insulin-treated groups received 1 to 4 UI of insulin daily for 8 wk. Each group was divided into sedentary or exercised rats. Trained groups were submitted to swimming (90 min/day, 5 days/wk, 8 wk). [Ca2+]i transient in left ventricular myocytes (LVM), oxidative stress in LV tissue, and mitochondrial functions in the heart were assessed. Diabetes reduced the amplitude and prolonged the times to peak and to half decay of the [Ca2+]i transient in LVM, increased NADPH oxidase-4 (Nox-4) expression, decreased superoxide dismutase (SOD), and increased carbonyl protein contents in LV tissue. In isolated mitochondria, diabetes increased Ca2+ uptake, susceptibility to permeability transition pore (MPTP) opening, uncoupling protein-2 (UCP-2) expression, and oxygen consumption but reduced H2O2 release. Swimming training corrected the time course of the [Ca2+]i transient, UCP-2 expression, and mitochondrial Ca2+ uptake. Insulin replacement further normalized [Ca2+]i transient amplitude, Nox-4 expression, and carbonyl content. Alongside these benefits, the combination of both therapies restored the LV tissue SOD and mitochondrial O2 consumption, H2O2 release, and MPTP opening. In conclusion, the combination of swimming training with insulin replacement was more effective in attenuating intracellular Ca2+ disruptions, oxidative stress, and mitochondrial dysfunctions in STZ-induced diabetic rat hearts.

scholarly journals Oxidative Stress and Mitochondrial Functions in the Intestinal Caco-2/15 Cell Line

PLoS ONE ◽  
2010 ◽  
Vol 5 (7) ◽  
pp. e11817 ◽  
Author(s):  
Rame Taha ◽  
Ernest Seidman ◽  
Genevieve Mailhot ◽  
François Boudreau ◽  
Fernand-Pierre Gendron ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Line ◽  
Mitochondrial Functions ◽  
And Mitochondrial Functions

scholarly journals Diabetes-induced increased oxidative stress in cardiomyocytes is sustained by a positive feedback loop involving Rho kinase and PKCβ2

2012 ◽  
Vol 303 (8) ◽  
pp. H989-H1000 ◽  
Author(s):  
Hesham Soliman ◽  
Anthony Gador ◽  
Yi-Hsuan Lu ◽  
Guorong Lin ◽  
Girish Bankar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Contractile Function ◽  
Rho Kinase ◽  
Underlying Mechanism ◽  
Diabetic Rat ◽  
Positive Feedback Loop ◽  
Rat Hearts ◽  
Inos Inhibition

We previously reported that acute inhibition of the RhoA/Rho kinase (ROCK) pathway normalized contractile function of diabetic rat hearts, but the underlying mechanism is unclear. Protein kinase C (PKC) β2 has been proposed to play a major role in diabetic cardiomyopathy at least in part by increasing oxidative stress. Further evidence suggests that PKC positively regulates RhoA expression through induction of inducible nitric oxide synthase (iNOS) in diabetes. However, in preliminary studies, we found that inhibition of ROCK itself reduced RhoA expression in diabetic hearts. We hypothesized that there is an interaction between RhoA/ROCK and PKCβ2 in the form of a positive feedback loop that sustains their activation and the production of reactive oxygen species (ROS). This was investigated in cardiomyocytes isolated from diabetic and control rat hearts, incubated with or without cytochalasin D or inhibitors of ROCK, RhoA, PKCβ2, or iNOS. Inhibition of RhoA and ROCK markedly attenuated the diabetes-induced increases in PKCβ2 activity and iNOS and RhoA expression in diabetic cardiomyocytes, while having no effect in control cells. Inhibition of PKCβ2 and iNOS also normalized RhoA expression and ROCK overactivation, whereas iNOS inhibition reversed the increase in PKCβ2 activity. Each of these treatments also normalized the diabetes-induced increase in production of ROS. Actin cytoskeleton disruption attenuated the increased expression and/or activity of all of these targets in diabetic cardiomyocytes. These data suggest that, in the diabetic heart, the RhoA/ROCK pathway contributes to contractile dysfunction at least in part by sustaining PKCβ2 activation and ROS production via a positive feedback loop that requires an intact cytoskeleton.

On the oxidative damage by cadmium to kidney mitochondrial functions

2019 ◽  
Vol 97 (2) ◽  
pp. 187-192 ◽  
Author(s):  
Natalia Pavón ◽  
Mabel Buelna-Chontal ◽  
Arturo Macías-López ◽  
Francisco Correa ◽  
Cristina Uribe-Álvarez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heavy Metals ◽  
Mitochondrial Dna ◽  
Oxidative Damage ◽  
Mitochondrial Dysfunctions ◽  
Mitochondrial Functions ◽  
Electrical Gradient ◽  
Radical Generation ◽  
Parameters Of Interest ◽  
Stimulation Of

In the kidney, the accumulation of heavy metals such as Cd2+ produces mitochondrial dysfunctions, i.e., uncoupling of the oxidative phosphorylation, inhibition of the electron transport through the respiratory chain, and collapse of the transmembrane electrical gradient. This derangement may be due to the fact that Cd2+ induces the transition of membrane permeability from selective to nonselective via the opening of a transmembrane pore. In fact, Cd2+ produces this injury through the stimulation of oxygen-derived radical generation, inducing oxidative stress. Several molecules have been used to avoid or even reverse Cd2+-induced mitochondrial injury, for instance, cyclosporin A, resveratrol, dithiocarbamates, and even EDTA. The aim of this study was to explore the possibility that the antioxidant tamoxifen could protect mitochondria from the deleterious effects of Cd2+. Our results indicate that the addition of 1 μmol/L Cd2+ to mitochondria collapsed the transmembrane electrical gradient, induced the release of cytochrome c, and increased both the generation of H2O2 and the oxidative damage to mitochondrial DNA (among other measured parameters). Of interest, these mitochondrial dysfunctions were ameliorated after the addition of tamoxifen.

Cardiomyocyte apoptosis induced by short-term diabetes requires mitochondrial GSH depletion

2005 ◽  
Vol 289 (2) ◽  
pp. H768-H776 ◽  
Author(s):  
Sanjoy Ghosh ◽  
Thomas Pulinilkunnil ◽  
Gloria Yuen ◽  
Girish Kewalramani ◽  
Ding An ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Apoptotic Cell ◽  
Buthionine Sulfoximine ◽  
Diabetic Rats ◽  
Cardiomyocyte Apoptosis ◽  
Diabetic Rat ◽  
Short Term ◽  
Rat Hearts ◽  
Cardiac Apoptosis ◽  
Cell Suicide

Oxidative stress due to excessive reactive oxygen species (ROS) and depleted antioxidants such as glutathione (GSH) can give rise to apoptotic cell death in acutely diabetic hearts and lead to heart disease. At present, the source of these cardiac ROS or the subcellular site of cardiac GSH loss [i.e., cytosolic (cGSH) or mitochondrial (mGSH) GSH] has not been completely elucidated. With the use of rotenone (an inhibitor of the electron transport chain) to decrease the excessive ROS in acute streptozotocin (STZ)-induced diabetic rat heart, the mitochondrial origin of ROS was established. Furthermore, mitochondrial damage, as evidenced by loss of membrane potential, increases in oxidative stress, and reduction in mGSH was associated with increased apoptosis via increases in caspase-9 and -3 activities in acutely diabetic hearts. To validate the role of mGSH in regulating cardiac apoptosis, l-buthionine-sulfoximine (BSO; 10 mmol/kg ip), which blocks GSH synthesis, or diethyl maleate (DEM; 4 mmol/kg ip), which inactivates preformed GSH, was administered in diabetic rats for 4 days after STZ administration. Although both BSO and DEM lowered cGSH, they were ineffective in reducing mGSH or augmenting cardiomyocyte apoptosis. To circumvent the lack of mGSH depletion, BSO and DEM were coadministered in diabetic rats. In this setting, mGSH was undetectable and cardiac apoptosis was further aggravated compared with the untreated diabetic group. In a separate group, GSH supplementation induced a robust amplification of mGSH in diabetic rat hearts and prevented apoptosis. Our data suggest for the first time that mGSH is crucial for modulating the cell suicide program in short-term diabetic rat hearts.

scholarly journals Carvedilol protected diabetic rat hearts via reducing oxidative stress

2006 ◽  
Vol 7 (9) ◽  
pp. 725-731 ◽  
Author(s):  
He Huang ◽  
Jiang Shan ◽  
Xiao-hong Pan ◽  
Hui-ping Wang ◽  
Ling-bo Qian
Keyword(s):  
Oxidative Stress ◽  
Diabetic Rat ◽  
Rat Hearts

Carvedilol Protects Early Diabetic Rat Hearts through Reducing Oxidative Stress

2005 ◽  
Author(s):  
He Huang ◽  
Jiang Shan ◽  
Xiao-Hong Pan ◽  
Xiao-Feng Bao ◽  
Ling-Bo Qian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Rat ◽  
Rat Hearts

Differential autocrine modulation of atrial and ventricular potassium currents and of oxidative stress in diabetic rats

2006 ◽  
Vol 290 (5) ◽  
pp. H1879-H1888 ◽  
Author(s):  
Yakhin Shimoni ◽  
Don Hunt ◽  
Keyun Chen ◽  
Teresa Emmett ◽  
Gary Kargacin
Keyword(s):  
Oxidative Stress ◽  
Renin Angiotensin System ◽  
Cell Voltage ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Ang Ii ◽  
A Cells ◽  
Ras Activation ◽  
Rat Hearts

The autocrine modulation of cardiac K+ currents was compared in ventricular and atrial cells (V and A cells, respectively) from Type 1 diabetic rats. K+ currents were measured by using whole cell voltage clamp. ANG II was measured by ELISA and immunofluorescent labeling. Oxidative stress was assessed by immunofluorescent labeling with dihydroethidium, a measure of superoxide ions. In V cells, K+ currents are attenuated after activation of the renin-angiotensin system (RAS) and the resulting ANG II-mediated oxidative stress. In striking contrast, these currents are not attenuated in A cells. Inhibition of the angiotensin-converting enzyme (ACE) also has no effect, in contrast to current augmentation in V cells. ANG II levels are enhanced in V, but not in A, cells. However, the high basal ANG II levels in A cells suggest that in these cells, ANG II-mediated pathways are suppressed, rather than ANG II formation. Concordantly, superoxide ion levels are lower in diabetic A than in V cells. Several findings indicate that high atrial natriuretic peptide (ANP) levels in A cells inhibit RAS activation. In male diabetic V cells, in vitro ANP (300 nM–1 μM, >5 h) decreases oxidative stress and augments K+ currents, but not when excess ANG II is present. ANP has no effect on ventricular K+ currents when the RAS is not activated, as in control males, in diabetic males treated with ACE inhibitor and in diabetic females. In conclusion, the modulation of K+ currents and oxidative stress is significantly different in A and V cells in diabetic rat hearts. The evidence suggests that this is largely due to inhibition of RAS activation and/or action by ANP in A cells. These results may underlie chamber-specific arrhythmogenic mechanisms.

Effects of empagliflozin on oxidative stress and endothelial dysfunction in STZ-induced Type 1 diabetic rat

2014 ◽  
Vol 9 (S 01) ◽  
Author(s):  
M Oelze ◽  
S Kröller-Schön ◽  
M Mader ◽  
E Zinßius ◽  
P Stamm ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Diabetic Rat
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