Paraspinal Muscle Contractile Function is Impaired in the ENT1 Deficient Mouse Model of Progressive Spine Pathology

Type 2 diabetes is characterized by reduced contractile force production and increased fatigability of skeletal muscle. While the maintenance of Ca2+ homeostasis during muscle contraction is a requisite for optimal contractile function, the mechanisms underlying muscle contractile dysfunction in type 2 diabetes are unclear. Here, we investigated skeletal muscle contractile force and Ca2+ flux during contraction and pharmacological stimulation in type 2 diabetic model mice ( db/db mice). Furthermore, we investigated the effect of treadmill exercise training on muscle contractile function. In male db/db mice, muscle contractile force and peak Ca2+ levels were both lower during tetanic stimulation of the fast-twitch muscles, while Ca2+ accumulation was higher after stimulation compared with control mice. While 6 wk of exercise training did not improve glucose tolerance, exercise did improve muscle contractile dysfunction, peak Ca2+ levels, and Ca2+ accumulation following stimulation in male db/db mice. These data suggest that dysfunctional Ca2+ flux may contribute to skeletal muscle contractile dysfunction in type 2 diabetes and that exercise training may be a promising therapeutic approach for dysfunctional skeletal muscle contraction. NEW & NOTEWORTHY The purpose of this study was to examine muscle contractile function and Ca2+ regulation as well as the effect of exercise training in skeletal muscle in obese diabetic mice ( db/db). We observed impairment of muscle contractile force and Ca2+ regulation in a male type 2 diabetic animal model. These dysfunctions in muscle were improved by 6 wk of exercise training.

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Telomerase-Deficient Mouse Model

Chromosomal Instability and Aging ◽

10.1201/9780203911709-26 ◽

2003 ◽

pp. 541-564

Keyword(s):

Mouse Model ◽

Deficient Mouse

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Effects of Regular Exercise Training on Skeletal Muscle Contractile Function

American Journal of Physical Medicine & Rehabilitation ◽

10.1097/01.phm.0000059336.40487.9c ◽

2003 ◽

Vol 82 (4) ◽

pp. 320-331 ◽

Cited By ~ 23

Author(s):

Robert H. Fitts

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Contractile Function ◽

Regular Exercise ◽

Muscle Contractile

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Cardiomyopathy, oxidative stress and impaired contractility in a rheumatoid arthritis mouse model

Heart ◽

10.1136/heartjnl-2018-312979 ◽

2018 ◽

Vol 104 (24) ◽

pp. 2026-2034 ◽

Cited By ~ 10

Author(s):

Gianluigi Pironti ◽

Alex Bersellini-Farinotti ◽

Nilesh M Agalave ◽

Katalin Sandor ◽

Teresa Fernandez-Zafra ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Oxidative Stress ◽

Heart Failure ◽

Mouse Model ◽

Posttranslational Modifications ◽

Contractile Function ◽

Joint Inflammation ◽

Left Ventricular ◽

Increased Risk ◽

Fractional Shortening

ObjectivesPatients with rheumatoid arthritis (RA) display an increased risk of heart failure independent of traditional cardiovascular risk factors. To elucidate myocardial disease in RA, we have investigated molecular and cellular remodelling of the heart in an established mouse model of RA.MethodsThe collagen antibody-induced arthritis (CAIA) RA mouse model is characterised by joint inflammation and increased inflammatory markers in the serum. We used CAIA mice in the postinflammatory phase that resembles medically controlled RA or RA in remission. Hearts were collected for cardiomyocyte isolation, biochemistry and histology analysis.ResultsHearts from mice subjected to CAIA displayed hypertrophy (heart/body weight, mean±SD: 5.9±0.8vs 5.1±0.7 mg/g, p<0.05), fibrosis and reduced left ventricular fractional shortening compared with control. Cardiomyocytes from CAIA mice showed reduced cytosolic [Ca2+]i transient amplitudes (F/F0, mean±SD: 3.0±1.2vs 3.6±1.5, p<0.05) that was linked to reductions in sarcoplasmic reticulum (SR) Ca2+ store (F/F0, mean±SD: 3.5±1.3vs 4.4±1.3, p<0.01) measured with Ca2+ imaging. This was associated to lower fractional shortening in the cardiomyocytes from the CAIA mice (%FS, mean±SD: 3.4±2.2 vs 4.6%±2.3%, p<0.05). Ca2+ handling proteins displayed oxidation-dependent posttranslational modifications that together with an increase in superoxide dismutase expression indicate a cell environment with oxidative stress.ConclusionsThis study shows that inflammation during active RA has long-term consequences on molecular remodelling and contractile function of the heart, which further supports that rheumatology patients should be followed for development of heart failure.

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Abstract 216: Tat Delivery of a Pten Peptide Inhibitor Has Direct Cardioprotective Effects and Improves Outcomes in Rodent Models of Cardiac Arrest

Circulation ◽

10.1161/circ.142.suppl_4.216 ◽

2020 ◽

Vol 142 (Suppl_4) ◽

Author(s):

Xiangdong Zhu ◽

Jing Li ◽

Huashan Wang ◽

Filip Gasior ◽

Chunpei Lee ◽

...

Keyword(s):

Cardiac Arrest ◽

Mouse Model ◽

Pyruvate Dehydrogenase ◽

Contractile Function ◽

Heart Function ◽

Isolated Heart ◽

Lactate Production ◽

Polyol Pathway ◽

Protective Effects ◽

Cardiac Arrest Survival

Introduction: We have recently shown that pharmacologic inhibition of PTEN significantly increases cardiac arrest survival in a mouse model, however, this protection required pretreatment 30 min prior to the arrest. To improve the onset of PTEN inhibition during cardiac arrest treatment, we have designed a TAT fused cell-permeable peptide (TAT-PTEN9c) for rapid tissue delivery and protection. Hypothesis: We hypothesized that TAT-PTEN9c interferes with the endogenous PTEN binding to its regulatory proteins, resulting in reduced PTEN activity, improved mouse survival and cardiac functional recovery. The improved survival is in part due to enhanced glycolysis and reduced shunting to polyol pathway and osmotic injury in heart and brain. Methods: TAT-PTEN9c (7.5 mg/kg) was given intravenously after CA in mouse to determine protective effects of the treatment on survival and heart function. Western blot was used to determine the efficacy of TAT-PTEN9c for enhancing Akt and PDH E1α activity. The effect of TAT-PTEN9c on sorbitol accumulation in tissues was measured by spectrophotometer using NAD as substrate. Direct effect of TAT-PTEN9c treatment on cardiac function were also measured in Langendorff model of isolated rat heart. Results: In the mouse model of cardiac arrest, survival was significantly increased in the TAT-PTEN9c treated group compared to saline controls at 4 h after CPR. The treated mice had increased Akt phosphorylation and pyruvate dehydrogenase dephosphorylation at R30 min in heart tissues with significantly decreased sorbitol content and reduced release of taurine and glutamate into blood, suggesting improved metabolic recovery and glucose utilization. For the isolated heart model, RPP was reduced by 25% for non-treatment groups following arrest. With TAT-PTEN9c treatment, cardiac contractile function was completely recovered. TAT-PTEN9c significantly increased lactate production at 20 min of reperfusion, indicating increased glycolysis. Conclusion: TAT-PTEN9c enhances Akt and pyruvate dehydrogenase activity and decrease glucose shunting to the polyol pathway in critical organs, preventing osmotic injury and early cardiovascular collapse and death.

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