Chronic exercise downregulates myocardial myoglobin and attenuates nitrite reductase capacity during ischemia–reperfusion

Nicholson, Chad K.; Lambert, Jonathan P; Chow, Chi Wing; Lefer, David J.; Calvert, John W.

doi:10.1016/j.yjmcc.2013.08.002

Cited by 14 publications

(13 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Surgical ligation of the left coronary artery, myocardial infarct size determination, Troponin-I measurements, echocardiography and invasive hemodynamics were performed similar to methods described previously [20, 21]. …”

Section: Methodsmentioning

confidence: 99%

“…Whole cell homogenates were obtained as previously described [20]. Mitochondrial fractions were obtained using the Mitochondria Isolation Kit (MITOISO1, Sigma).…”

Section: Methodsmentioning

confidence: 99%

“…Mitochondrial fractions were obtained using the Mitochondria Isolation Kit (MITOISO1, Sigma). Western blot analysis was performed as described previously [20]. …”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

DJ-1 protects the heart against ischemia–reperfusion injury by regulating mitochondrial fission

Shimizu

Lambert

Nicholson

et al. 2016

Journal of Molecular and Cellular Cardiology

Self Cite

View full text Add to dashboard Cite

Recent data indicates that DJ-1 plays a role in the cellular response to stress. Here, we aimed to examine the underlying molecular mechanisms mediating the actions of DJ-1 in the heart following myocardial ischemia-reperfusion (I/R) injury. In response to I/R injury, DJ-1 KO mice displayed increased areas of infarction and worsened left ventricular function when compared to WT mice, confirming a protective role for DJ-1 in the heart. In an effort to evaluate the potential mechanism(s) responsible for the increased injury in DJ-1 KO mice, we focused on SUMOylation, a post-translational modification process that regulates various aspects of protein function. DJ-1 KO hearts after I/R injury were found to display enhanced accumulation of SUMO-1 modified proteins and reduced SUMO-2/3 modified proteins. Further analysis, revealed that the protein expression of the de-SUMOylation enzyme SENP1 was reduced, whereas the expression of SENP5 was enhanced in DJ-1 KO hearts after I/R injury. Finally, DJ-1 KO hearts were found to display enhanced SUMO-1 modification of dynamin-related protein 1, excessive mitochondrial fission, and dysfunctional mitochondria. Our data demonstrates that the activation of DJ-1 in response to myocardial I/R injury protects the heart by regulating the SUMOylation status of Drp1 and attenuating excessive mitochondrial fission.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Whole cell homogenates were obtained as previously described [20]. Mitochondrial fractions were obtained using the Mitochondria Isolation Kit (MITOISO1, Sigma).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

DJ-1 protects the heart against ischemia–reperfusion injury by regulating mitochondrial fission

Shimizu

Lambert

Nicholson

et al. 2016

Journal of Molecular and Cellular Cardiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, the mechanism by which this occurs is still unclear 6 , 8 , 18 . According to the retrieved studies, the main proposed mechanisms include increased production of heat shock proteins (HSPs) 31 , 33 , involvement of the NO pathway 11 , 12 , 19 , 20 , increased cardiac antioxidant activity associated with decreased ROS production in myocardial mitochondria 13 - 15 , 21 , 22 , 25 , improved sarcolemmal and mitochondrial KATP channel function 34 - 36 , and activation of the opioid system 9 , 37 , 38 .…”

Section: Discussionmentioning

confidence: 99%

Mechanisms Involved in Exercise-Induced Cardioprotection: A Systematic Review

Borges¹,

Lessa²

2015

Arquivos Brasileiros De Cardiologia

View full text Add to dashboard Cite

BackgroundAcute myocardial infarction is the leading cause of morbidity and mortality worldwide. Furthermore, research has shown that exercise, in addition to reducing cardiovascular risk factors, can also protect the heart against injury due to ischemia and reperfusion through a direct effect on the myocardium. However, the specific mechanism involved in exerciseinduced cardiac preconditioning is still under debate.ObjectiveTo perform a systematic review of the studies that have addressed the mechanisms by which aerobic exercise promotes direct cardioprotection against ischemia and reperfusion injury.MethodsA search was conducted using MEDLINE, Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde, and Scientific Electronic Library Online databases. Data were extracted in a standardized manner by two independent researchers, who were responsible for assessing the methodological quality of the studies.ResultsThe search retrieved 78 studies; after evaluating the abstracts, 30 studies were excluded. The manuscripts of the remaining 48 studies were completely read and, of these, 20 were excluded. Finally, 28 studies were included in this systematic review.ConclusionOn the basis of the selected studies, the following are potentially involved in the cardioprotective response to exercise: increased heat shock protein production, nitric oxide pathway involvement, increased cardiac antioxidant capacity, improvement in ATP-dependent potassium channel function, and opioid system activation. Despite all the previous investigations, further research is still necessary to obtain more consistent conclusions.

show abstract

“…Ventricular tissue was used for Western blot analysis, which was performed as previously described (23 Real-time PCR. Ventricular mRNA was quantified using TaqMan primers from Life Technologies and performed as previously described (36).…”

Section: Animalsmentioning

confidence: 99%

Sustained release nitrite therapy results in myocardial protection in a porcine model of metabolic syndrome with peripheral vascular disease

Bradley

Islam

Polhemus

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

Nitrite, a storage form of NO, can mediate vascular function during pathological conditions when endogenous NO is reduced. The aims of the present study were to characterize the effects of severe MetS and obesity on dyslipidemia, myocardial oxidative stress, and endothelial NO synthase (eNOS) regulation in the obese Ossabaw swine (OS) model and to examine the effects of a novel, sustained-release formulation of sodium nitrite (SR-nitrite) on coronary vascular reactivity and myocardial redox status in obese OS subjected to critical limb ischemia (CLI). After 6 mo of an atherogenic diet, obese OS displayed a MetS phenotype. Obese OS had decreased eNOS functionality and NO bioavailability. In addition, obese OS exhibited increased oxidative stress and a significant reduction in antioxidant enzymes. The efficacy of SR-nitrite therapy was examined in obese OS subjected to CLI. After 3 wk of treatment, SR-nitrite (80 mg·kg Ϫ1 ·day Ϫ1 bid po) increased myocardial nitrite levels and eNOS function. Treatment with SR-nitrite reduced myocardial oxidative stress while increasing myocardial antioxidant capacity. Ex vivo assessment of vascular reactivity of left anterior descending coronary artery segments demonstrated marked improvement in vasoreactivity to sodium nitroprusside but not to substance P and bradykinin in SR-nitrite-treated animals compared with placebo-treated animals. In conclusion, in a clinically relevant, large-animal model of MetS and CLI, treatment with SR-nitrite enhanced myocardial NO bioavailability, attenuated oxidative stress, and improved ex vivo coronary artery vasorelaxation. METABOLIC SYNDROME (MetS) is a multifactorial disease that is characterized by a number of risk factors including obesity, hypertension, dyslipidemia, and hyperglycemia (27). Clinically, MetS is associated with an increased risk for the development of cardiovascular disease. In patients with preexisting atherosclerotic vascular disease, such as peripheral artery disease (PAD), MetS exacerbates vascular damage by impairing vascular endothelial and smooth muscle function (37). Furthermore, PAD patients with MetS have an increased incidence of acute coronary syndromes, resulting in significant cardiovascular morbidity and mortality (5,16,20,21).One of the earliest manifestations of cardiovascular diseases, including PAD, is a loss of endothelial function characterized by dysfunction of endothelial nitric oxide (NO) synthase (eNOS) and reduced NO bioavailability (7,19,44). Our laboratory has recently published data (40) demonstrating significant reductions in circulating NO bioavailability in patients with critical limb ischemia (CLI), a severe manifestation of PAD.Nitrite is recognized as an important physiological storage reservoir of NO in the blood and tissues that protects various organs against ischemic injury (10,12,31). During pathological conditions, nitrite is rapidly reduced to NO to restore NO levels and promote organ homeostasis and survival (10,12,31). Moreover, endogenous nitrite has been shown to exert endocrine a...

show abstract

Chronic exercise downregulates myocardial myoglobin and attenuates nitrite reductase capacity during ischemia–reperfusion

Cited by 14 publications

References 54 publications

DJ-1 protects the heart against ischemia–reperfusion injury by regulating mitochondrial fission

DJ-1 protects the heart against ischemia–reperfusion injury by regulating mitochondrial fission

Mechanisms Involved in Exercise-Induced Cardioprotection: A Systematic Review

Sustained release nitrite therapy results in myocardial protection in a porcine model of metabolic syndrome with peripheral vascular disease

Contact Info

Product

Resources

About