Peroxisome Proliferator–Activated Receptor γ Coactivator-1 (PGC-1) Regulatory Cascade in Cardiac Physiology and Disease

Finck, Brian N.; Kelly, Daniel P.

doi:10.1161/circulationaha.107.670588

Cited by 251 publications

(197 citation statements)

References 100 publications

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“…In the normal heart, AMP-activated protein kinase (AMPK) protects cardiac cells from perturbations in energy homeostasis via activation of catabolic pathways to generate ATP. DOX reduces the levels of AMPK and its basic activation state, leading to decreased phosphorylation of antiacetyl-CoA carboxylase (ACC), an AMPK downstream target [39][40][41][42][43]. Lack of ACC inhibition results in impairment of fatty acid oxidation.…”

Section: ) Alterations In Cardiac Energy Metabolismmentioning

confidence: 99%

Aerobic Exercise Training as a Potential Cardioprotective Strategy to Attenuate Doxorubicin-Induced Cardiotoxicity

Kouzi

Uddin

2016

J Pharm Pharm Sci

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Doxorubicin is one of the most commonly used cytotoxic anticancer drugs against several cancers. Although a highly effective anticancer drug, the clinical use of doxorubicin is severely limited by its cardiotoxicity which results in morbidity, poor quality of life, and premature mortality. Only very few clinically accepted methods to minimize doxorubicin-induced cardiac injury are available today, but none of them have proven to be completely successful. Due to limited alternative strategies, a number of potential cardioprotective therapies are currently being investigated for treating and/or preventing doxorubicin-induced cardiotoxicity. Of these potential strategies, aerobic exercise training is the only nonpharmacologic strategy that shows a great deal of promise. Although there are no published human clinical trials, evidence from numerous animal studies suggests that aerobic exercise training, administered prior to, during and/or following doxorubicin therapy, is protective against doxorubicin-induced cardiac injury. Protective properties of exercise training against the cardiotoxicity of doxorubicin have been attributed to a number of potential molecular mechanisms including: enhancing the production of endogenous antioxidant machineries; regulating proapoptotic signaling; stimulating the release, mobilization and homing of cardiac progenitor cells; limiting myocyte turnover; eliciting favorable adaptations in myocardial calcium handling and preventing calcium overload; modulating cardiac AMPK activity; downregulating cardiac autophagy/lysosomal signaling; and reducing myocardial doxorubicin accumulation. Further preclinical and clinical research is needed to decipher and refine the molecular mechanisms underlying the cardioprotective effects of exercise training, as well as to define the nature and magnitude of the effect of exercise on doxorubicin-induced cardiotoxicity in cancer patients. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Section: ) Alterations In Cardiac Energy Metabolismmentioning

confidence: 99%

Aerobic Exercise Training as a Potential Cardioprotective Strategy to Attenuate Doxorubicin-Induced Cardiotoxicity

Kouzi

Uddin

2016

J Pharm Pharm Sci

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“…Due to the limited ability for substrate storage, the heart function stringently depends on the ATP-generating pathway (Huss and Kelly, 2005). Mitochondria provide the energy required for cardiomyocytes function (Finck and Kelly, 2007). Mitochondrial number in the cardiomyocytes is dynamically regulated in response to cardiac energy demands (Lehman et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial network in the heart

Zhou

Gao

et al. 2012

Protein Cell

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Mitochondria are subcellular organelles that provide energy for the cell. They form a dynamic tubular network and play an important role in maintaining the cell function and integrity. Heart is a powerful organ that supplies the motivation for circulation, thereby requiring large amounts of energy. Thus, the healthiness of cardiomyocytes and mitochondria is necessary for the normal cardiac function. Mitochondria not only lie in the center of the cell apoptotic pathway, but also are the major source of reactive oxygen species (ROS) generation. Mitochondrial morphological change includes fission and fusion that are regulated by a large number of proteins. In this review we discuss the regulators of mitochondrial fission/fusion and their association with cell apoptosis, autophagy and ROS production in the heart.

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“…Отмечался стеатоз и накопление перекисных продуктов в миокарде, что свидетельствовало о липотоксическом компоненте кардиомиопатических изменений. Неконтролируе-мое окисление ЖК, накопление токсических продук-тов и перекисей является причиной кардиомиопатии [8]. Мыши с удаленным геном РАППα демонстри-руют ранний миокардиофиброз.…”

Section: раппα в сердечной мышцеunclassified

PEROXYSOME PROLIFERATOR-ACTIVATED RECEPTORS AND THEIR COACTIVATOR — PGC-1α — IN PHYSIOLOGY AND PATHOLOGY OF MYOCARDIUM

Расін¹

2015

Ross. kardiol. ž.

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Рецепторы, активируемые пролифераторами пероксисом (PPAR) α и β/δ управ-ляют экспрессией генов окисления жирных кислот (ЖК), являющихся источником 70-90% АТФ в миокарде. PPARα контролирует окисление ЖК и влияет на энерге-тический гомеостаз миокарда, главным образом, через поставку циркулирующих ЖК из печени, а PPARγ предохраняет миокард от избытка ЖК и липотоксичности путем перераспределения потоков ЖК в адипоциты. PPARβ/δ является главным регулятором липидного обмена в мышцах, составляющих до 50% массы тела. Система PPAR/PGC-1α (главным образом, PPARα/PGC-1α) контролирует биоге-нез митохондрий и, таким образом, обеспечивает возможность приспособления миокарда к внезапно возникающей (стрессорной) нагрузке. Экспрессия PPARα/ PGC-1α увеличивается при физиологических формах гипертрофии миокарда: в постнатальном развитии и физической тренировке и уменьшается при патоло-гических формах гипертрофии миокарда и сердечной недостаточности. Дис-функция регуляторной системы -PPAR/ PGC-1α может быть одним из патогене-тических механизмов развития кардиомиопатий, а сигнальные пути этой сис-темы -объектом терапевтических воздействий. PEROXYSOME PROLIFERATOR-ACTIVATED RECEPTORS AND THEIR COACTIVATOR -PGC-1α -IN PHYSIOLOGY AND PATHOLOGY OF MYOCARDIUMRasin M. S. PPAR α controls FA oxydation and influences myocardial energy metabolism homeostasis, mostly through the supplement of circulating FA from the liver, and PPARγ prevent the excess of FA in myocardium with lipotoxicity prevented by switching the flow of FA to adipocytes. PPARβ/δ is the main regulator of lipid metabolism on muscles, that are 50% of body mass. The PPAR/PGC-1α system (mostly PPARα/PGC-1α) controls the biogenesis of mitochondria and hence makes available the possibility to adaptate myocardium for sudden (stress) exertion. Expression of PPARα/PGC-1α increases in physiologic forms of myocardial hypertrophy: in postnatal period and physical entraining, and decreases in pathological forms of myocardial hypertrophy and heart failure. Dysfunction of regulatory system PPAR/ PGC-1α might be one of the pathogenetic mechanisms of cardiomyopathy development, and signal pathways for the system -the object for therapeutic interventions.

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Peroxisome Proliferator–Activated Receptor γ Coactivator-1 (PGC-1) Regulatory Cascade in Cardiac Physiology and Disease

Cited by 251 publications

References 100 publications

Aerobic Exercise Training as a Potential Cardioprotective Strategy to Attenuate Doxorubicin-Induced Cardiotoxicity

Aerobic Exercise Training as a Potential Cardioprotective Strategy to Attenuate Doxorubicin-Induced Cardiotoxicity

Mitochondrial network in the heart

PEROXYSOME PROLIFERATOR-ACTIVATED RECEPTORS AND THEIR COACTIVATOR — PGC-1α — IN PHYSIOLOGY AND PATHOLOGY OF MYOCARDIUM

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