Endurance training reverts heart mitochondrial dysfunction, permeability transition and apoptotic signaling in long-term severe hyperglycemia

Lumini-Oliveira, José; Magalhães, José; Pereira, Cláudia V.; Moreira, Ana C.; Oliveira, Paulo J.; Ascensão, António

doi:10.1016/j.mito.2010.07.005

Cited by 57 publications

(36 citation statements)

References 65 publications

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“…Mitochondrial dysfunction in type 1 diabetic heart tissue is the result of inhibition of the respiratory chain (33)(34)(35), oxidative stress ( 35,36 ), and decreased resistance to Ca 2+ - ( 37,38 ) and oxidative stressinduced mPTP opening ( 39,40 ).…”

Section: Antibodiesmentioning

confidence: 99%

Lactosylceramide contributes to mitochondrial dysfunction in diabetes

Novgorodov

Riley

et al. 2016

Journal of Lipid Research

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This article is available online at http://www.jlr.orgCompelling epidemiological and clinical data indicate that diabetes mellitus increases the risk for cardiac dysfunction and heart failure independently of other risk factors, such as coronary disease and hypertension. Lipotoxicity is an important contributor to cardiac dysfunction in both type 1 ( 1, 2 ) and type 2 ( 3-6 ) diabetes, which are characterized by excessive accumulation of triacylglycerols, long-chain acyl-CoAs, diacylglycerols, and ceramides in myocardium. Correlation of the increased ceramide level with development of diabetic cardiomyopathy has attracted special attention in recent years because of the well-documented ability of this sphingolipid to regulate a number of cell processes, including cell proliferation, growth arrest, differentiation and apoptosis, and the mediation of responses to stress stimuli .Ceramide is a hub of sphingolipid metabolism ( 7,8 ). The balance between ceramide-producing pathways and pathways that consume it dictates ceramide level in the cell. The de novo ceramide biosynthesis pathway, one of the major ceramide producing pathways, localizes in the endoplasmic reticulum (ER) and starts with the condensation of serine and palmitoyl-CoA producing 3-ketosphingonine, which, in turn, is rapidly converted to dihydrosphingosine. Subsequent acylation of dihydrosphingosine by a set of (dihydro)ceramide synthases (CerSs) gives rise to dihydroceramide. Finally, the removal of two hydrogens from the fatty acid chain of dihydroceramide by desaturase leads to the formation of ceramide. Other possible contributors to elevated ceramide level are: hydrolysis of SM catalyzed by SMases, Abstract Sphingolipids have been implicated as key mediators of cell-stress responses and effectors of mitochondrial function. To investigate potential mechanisms underlying mitochondrial dysfunction, an important contributor to diabetic cardiomyopathy, we examined alterations of cardiac sphingolipid metabolism in a mouse with streptozotocininduced type 1 diabetes. Diabetes increased expression of desaturase 1, (dihydro)ceramide synthase (CerS)2, serine palmitoyl transferase 1, and the rate of ceramide formation by mitochondria-resident CerSs, indicating an activation of ceramide biosynthesis. However, the lack of an increase in mitochondrial ceramide suggests concomitant upregulation of ceramide-metabolizing pathways. Elevated levels of lactosylceramide, one of the initial products in the formation of glycosphingolipids were accompanied with decreased respiration and calcium retention capacity (CRC) in mitochondria from diabetic heart tissue. In baseline mitochondria, lactosylceramide potently suppressed state 3 respiration and decreased CRC, suggesting lactosylceramide as the primary sphingolipid responsible for mitochondrial defects in diabetic hearts. Moreover, knocking down the neutral ceramidase (NCDase) resulted in an increase in lactosylceramide level, suggesting a crosstalk between glucosylceramide synthase-and NCDase-mediated ceramide utiliz...

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Section: Antibodiesmentioning

confidence: 99%

Lactosylceramide contributes to mitochondrial dysfunction in diabetes

Novgorodov

Riley

et al. 2016

Journal of Lipid Research

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“…Caspase 3 and 8 activities were determined by following the detection of the chromophore p-nitroanilide after cleavage from the labeled substrate Ac-LEHD-p-nitroanilide at 405 nm as previously described (Lumini-Oliveira et al, 2011). The method was calibrated with known concentrations of p-nitroanilide (Calbiochem, UK).…”

Section: Caspase Activitymentioning

confidence: 99%

Endurance training and chronic intermittent hypoxia modulate in vitro salicylate-induced hepatic mitochondrial dysfunction

et al. 2012

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“…This is likely to lead to subsequent improvement in mitochondrial calcium content and limit dysfunction, but the effects of prior training on skeletal muscle mitochondria has not been well described. In cardiac tissue, it remains controversial whether exercise training confers protection against calcium-related insult (Lumini-Oliveira et al 2011). Cardiac tissue, however, is not normally exposed to the large calcium loads or high eccentric loads that the skeletal muscle experiences.…”

Section: Introductionmentioning

confidence: 99%

Specific training improves skeletal muscle mitochondrial calcium homeostasis after eccentric exercise

et al. 2012

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There is limited understanding of the mitochondrial adaptation following repeated eccentric exercise bouts, a model resulting in muscle adaptation known as the repeat bout effect. It was hypothesized that downhill training would reduce mitochondrial calcium content (MCC) post an acute eccentric bout with concurrent improvements in mitochondrial respiratory function. Thirty-four Sprague-Dawley rats were divided into four groups: control (N), control with acute eccentric exercise (N (ecc)), trained control (X) and trained with acute eccentric exercise (X (ecc)). Training for X and X (ecc) consisted of 30 min per day for five consecutive days of downhill treadmill running. The acute eccentric exercise bout was a -14° treadmill exercise for 90 min performed 2 weeks after the training period. Animals were killed 48 h post-exercise. Isolated mitochondria from the red quadriceps allowed for the measure of mitochondrial respiratory indices and MCC. Calpain activity and heat shock protein 72 expression (HSP72) were also measured. MCC dramatically increased following the acute bout of eccentric exercise in N (ecc) (p < 0.001), but did not change in X (ecc). Mitochondrial respiratory function tended to be slightly depressed in N (ecc) (state 3 respiration, p = 0.053; respiratory control ratio, p = 0.098) and unaltered in X (ecc). Previous training altered the calpain and heat shock protein response to an acute bout of eccentric exercise. The results suggest that downhill exercise training improves mitochondrial calcium homeostasis following an acute bout of prolonged eccentric exercise and may stabilize mitochondrial respiratory function. These improvements coincide with a reduction in calpain activity and heat shock protein upregulation.

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Endurance training reverts heart mitochondrial dysfunction, permeability transition and apoptotic signaling in long-term severe hyperglycemia

Cited by 57 publications

References 65 publications

Lactosylceramide contributes to mitochondrial dysfunction in diabetes

Lactosylceramide contributes to mitochondrial dysfunction in diabetes

Endurance training and chronic intermittent hypoxia modulate in vitro salicylate-induced hepatic mitochondrial dysfunction

Specific training improves skeletal muscle mitochondrial calcium homeostasis after eccentric exercise

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