Metabolic Stress—Signaling and Metabolic Adaptation

Balakrishnan, Preetha L.; Liebe, Theresa; Amro, Elias; Dhaka, Lajwanti; Heinzel, Thorsten; Heller, Regine

doi:10.1016/b978-0-12-814253-0.00012-7

Cited by 3 publications

(4 citation statements)

References 93 publications

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“…It determines the activation of ATP-generating catabolic processes (beta-oxidation of fatty acids or glycolysis) and the inactivation of energy-consuming anabolic processes. AMPK can determine in an insulin-independent way the uptake of glucose into the ischemic heart cell, but it can also directly modulate by phosphorylating key enzymes in carbohydrate, lipid, or protein metabolism, such as the inactivation of acetyl-CoA carboxylase (ACC), the enzyme that catalyzes the key step in the de novo synthesis of fatty acids, the transformation of acetyl-CoA into malonyl-CoA, or the activation of PFK-2 and implicitly of glycolysis, but also of the Akt substrate 160, a protein that determines the incorporation of GLUT-4 transporters for glucose in the cell membrane [29,30].…”

Section: Biochemical Changes During Exercisementioning

confidence: 99%

Biochemical Aspects That Lead to Abusive Use of Trimetazidine in Performance Athletes: A Mini-Review

Pușcaș,

Ștefănescu,

Vari

et al. 2024

IJMS

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Trimetazidine (TMZ), used for treating stable angina pectoris, has garnered attention in the realm of sports due to its potential performance-enhancing properties, and the World Anti-Doping Agency (WADA) has classified TMZ on the S4 list of prohibited substances since 2014. The purpose of this narrative mini-review is to emphasize the biochemical aspects underlying the abusive use of TMZ among athletes as a metabolic modulator of cardiac energy metabolism. The myocardium’s ability to adapt its energy substrate utilization between glucose and fatty acids is crucial for maintaining cardiac function under various conditions, such as rest, moderate exercise, and intense effort. TMZ acts as a partial inhibitor of fatty acid oxidation by inhibiting 3-ketoacyl-CoA thiolase (KAT), shifting energy production from long-chain fatty acids to glucose, reducing oxygen consumption, improving cardiac function, and enhancing exercise capacity. Furthermore, TMZ modulates pyruvate dehydrogenase (PDH) activity, promoting glucose oxidation while lowering lactate production, and ultimately stabilizing myocardial function. TMZs role in reducing oxidative stress is notable, as it activates antioxidant enzymes like glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). In conclusion, TMZs biochemical mechanisms make it an attractive but controversial option for athletes seeking a competitive edge.

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Section: Biochemical Changes During Exercisementioning

confidence: 99%

Biochemical Aspects That Lead to Abusive Use of Trimetazidine in Performance Athletes: A Mini-Review

Pușcaș,

Ștefănescu,

Vari

et al. 2024

IJMS

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“…In particular, three sirtuins, SIRT3, SIRT4, and SIRT5 reside inside the mitochondrial matrix where they regulate proteins involved in metabolic reactions, energy production, antioxidant pathways, apoptosis, and autophagy, thus promoting mitochondrial homeostasis (18,19). These targets, including SOD2, FOXO, p53, AMP-activated protein kinase (AMPK), and mammalian target of rapamycin (mTOR) are post-translationally modified by sirtuins, and allow a rapid homeostatic metabolic response to changes in energy expenditure/supply ratio, which occurs in several circumstances, such as calorie restriction (CR), fasting, physical exercise, and metabolic stress (Figure 1) (18,20,21).…”

Section: Mitochondrial Sirtuinsmentioning

confidence: 99%

Redox Homeostasis in Cardiovascular Disease: The Role of Mitochondrial Sirtuins

et al. 2022

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Cardiovascular disease (CVD) is still the leading cause of death worldwide. Despite successful advances in both pharmacological and lifestyle strategies to fight well-established risk factors, the burden of CVD is still increasing. Therefore, it is necessary to further deepen our knowledge of the pathogenesis of the disease for developing novel therapies to limit even more its related morbidity and mortality. Oxidative stress has been identified as a common trait of several manifestations of CVD and could be a promising target for innovative treatments. Mitochondria are a major source of oxidative stress and sirtuins are a family of enzymes that generate different post-translational protein modifications, thus regulating important cellular processes, including cell cycle, autophagy, gene expression, and others. In particular, three sirtuins, SIRT3, SIRT4, and SIRT5 are located within the mitochondrial matrix where they regulate energy production and antioxidant pathways. Therefore, these sirtuins are strongly involved in the balance between oxidant and antioxidant mechanisms. In this review, we summarize the activities of these sirtuins with a special focus on their role in the control of oxidative stress, in relation to energy metabolism, atherosclerosis, and CVD.

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“…Cells respond to changes in available nutrients (Balakrishnan et al, 2018; Lanning et al, 2017; Lin and Hardie, 2018; Saxton and Sabatini, 2017; Yang et al, 2013; Yang and Vousden, 2016) by adjusting their metabolic pathways to maintain homeostasis (Cairns et al, 2011; Moon et al, 2019). Under periods of high nutrient availability, cellular signaling pathways enable anabolism and cell growth (Yang et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Under periods of high nutrient availability, cellular signaling pathways enable anabolism and cell growth (Yang et al, 2013). In contrast, under periods of nutrient insufficiency, key biochemical pathways enable catabolism and restoration of metabolic homeostasis (Balakrishnan et al, 2018). For instance, AMP-activated protein kinase (AMPK) is a key cellular sensor of metabolic stress (Herzig and Shaw, 2018; Lin and Hardie, 2018).…”

Section: Introductionmentioning

confidence: 99%

AMP-activated protein kinase (AMPK) is required for recovery from metabolic stress induced by ultrasound microbubble treatment

Uchenunu

Botelho

et al. 2022

Preprint

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Ultrasound and microbubbles (USMB) is a promising strategy for cancer therapy. USMB can induce a variety of effects on cells including transient formation of plasma membrane pores (sonoporation) and enhanced endocytosis, which enhance drug delivery, and can also lead to enhanced cell death. However, the outcomes of USMB on cell physiology are heterogeneous, in that USMB elicits cell death in a proportion of cells while exerting minimal effects on others. This suggests that mechanisms of adaptation following USMB allow some cells to survive and/or proliferate. The molecular mechanisms of adaptation to USMB-induced stress remain poorly understood, thus potentially hindering broad therapeutic applications of USMB. Herein, we used several triple negative breast cancer cells to study the effect of USMB-induced metabolite stress and the role of AMPK as a response to this stress. We found that USMB alters steady-state levels of amino acids, glycolytic intermediates, and citric acid cycle intermediates. USMB treatment acutely reduces ATP levels and stimulates AMP-activated protein kinase (AMPK) phosphorylation and activation. Further, AMPK is required to restore ATP levels in cells that survived the initial insult and support cell proliferation post-USMB treatment. These results suggest that AMPK and metabolic perturbations are likely determinants of the anti-neoplastic efficacy of USMB treatment.

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Metabolic Stress—Signaling and Metabolic Adaptation

Cited by 3 publications

References 93 publications

Biochemical Aspects That Lead to Abusive Use of Trimetazidine in Performance Athletes: A Mini-Review

Biochemical Aspects That Lead to Abusive Use of Trimetazidine in Performance Athletes: A Mini-Review

Redox Homeostasis in Cardiovascular Disease: The Role of Mitochondrial Sirtuins

AMP-activated protein kinase (AMPK) is required for recovery from metabolic stress induced by ultrasound microbubble treatment

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