Primary Stress Damage of the Heart
Felix Z. Meerson in Adaptive Protection of The Heart: Protecting Against Stress and Ischemic Damage, 2019
This chapter discusses disturbances of metabolism, structure, and function after the cessation of stress; hence they are not just a reaction to stress, but relatively stable sequelae of a damage inflicted during stress. It also discusses that adrenergic and parasympathetic regulation are known to be most widely represented in the cardiac conducting system, which is also the most dependent for its energy provision on glycolysis profoundly upset in stress. The chapter provides some possible means of protection against the stress damage stemming from the concept of its pathogenesis. It presents the data on the disturbances to the energy metabolism and membrane ionic transport have been obtained upon a single stress not very rich in emotiogenic moments. The observed injury to the conducting system and the working myocardium drastically increase the heterogeneity of the heart and, as we shall see, upset its electric stability.
Glycolysis
Raymond S. Ochs in Metabolic Structure and Regulation, 2017
Glycolysis serves in the critical role of a connector to other pathways. This chapter considers the reactions common to most glycolytic pathways, or canonical glycolysis. The intermediates of glycolysis have been measured extensively in three tissues: red cells, liver, and skeletal muscle. The chapter details the major division of metabolic reactions between two types: near-equilibrium and the metabolically irreversible. The concept of energy coupling applies not just to an enzymatic mechanism, but to a metabolic pathway. A comparison of standard and actual free energies can be illustrated for glycolysis. A major role for glycolysis is the production of adenosine triphosphate from adenosine diphosphate. In the absence of mitochondrial pathways, this is the only route for the provision of energy for a cell. For all cells, the use of glycolytic intermediates as intersection points (pathway intermediates) of other pathways is an equally important function.
Conclusion
Shaun Phillips in Fatigue in Sport and Exercise, 2015
This conclusion presents closing thoughts of the concepts covered in preceding chapters of this book. The book introduces some of the main ways in which fatigue can be measured and quantified. Wider investigation into the dynamics of anaerobic glycolysis and the fate of intramuscular lactate has completely reshaped understanding of the role of lactate/lactic acid in the fatigue process. The book focuses on some of the most prevalent fatigue hypotheses that have produced significant research interest and/or have entered public consciousness, and some contemporary issues in fatigue research. An understanding of fatigue in sport and exercise has expanded and deepened exponentially in the last few decades, due in part to the development of new technologies and research methodologies. The chapter provides some hints and tips for maintaining a contemporary knowledge base in sport and exercise fatigue, and as well as some things to be aware of to ensure that knowledge is being gained from the most appropriate and trusted sources.
Myricetin nanoliposomes induced SIRT3-mediated glycolytic metabolism leading to glioblastoma cell death
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Gang Wang, Jun-Jie Wang, Yu-Zhu Wang, Shi Feng, Gao Jing, Xing-Li Fu
As the most aggressive and malignant glioma, glioblastoma multiforme (GBM) abnormally expresses genes that mediate glycolytic metabolism and tumour cell growth. In this study, we investigated myricetin incorporated nanoliposomes and ascertained their prospect in effectively treating cancer via the employment of the GBM cell line DBTRG-05MG. Notably, the myricetin nanoliposomes (MYR-NLs) displayed potent inhibition of proliferation and significantly regulated the levels of proteins related to both glycolytic metabolism and cell survival. Most importantly, SIRT3 and phosphorylated p53 were also down-regulated by MYR-NLs, indicating that the MYR-NLs inhibited GBM cell growth through the SIRT3/p53-mediated PI3K/Akt-ERK and mitochondrial pathways. Our findings thus provide rational evidence that liposomal myricetin targeted at alternative cell death pathways may be a useful adjuvant therapy in glioblastoma treatment.
Tumor cells and memory T cells converge at glycolysis
Published in Cancer Biology & Therapy, 2014
Swathi Karthikeyan, Jean-Francois Geschwind, Shanmugasundaram Ganapathy-Kanniappan
In the immune system, activation of naïve T (Tn) cells into effector T cells (Teff) involves a metabolic switch to glycolysis to promote rapid proliferation and differentiation. In the October issue of The Journal of Clinical Investigation, Sukumar et al. have demonstrated that in CD8+ memory T (Tems) cells glycolytic phenotype contributes to the shortened lifespan of Tems. Conversely, inhibition of glycolysis in Tems not only extended their viability but also augmented desirable properties. Notably, they also demonstrate that glycolytic inhibition during the ex vivo clonal expansion of tumor-specific Tems enhanced their antitumor function. Overall, the data suggest that an antiglycolytic strategy targeting the Tems could enhance antitumor immune response. On the other hand, cancer cells have long been known to exhibit metabolic reprogramming which involves a shift toward glycolysis (the conversion of glucose into lactate) to facilitate uninterrupted growth. Interestingly, antiglycolytic treatment of cancer cells has been known to trigger antitumor immune response as well. Taken together, it is probable that a strategy involving concurrent inhibition of glycolysis in tumor cells and Tems could promote a dual attack on cancer by inducing an effective antitumor immune response and an immunogenic chemotherapy.
Glycolytic inhibitor 2-deoxy-
Published in Leukemia & Lymphoma, 2015
Yu-Yang Pang, Ting Wang, Fang-Yuan Chen, Ying-Li Wu, Xia Shao, Fei Xiao, Hong-Hui Huang, Hua Zhong, Ji-Hua Zhong
Metabolic reprogramming is linked to tumorigenesis, disease progression, clinical outcome and resistance to chemotherapy. However, the significance of glycolytic metabolism in non-Hodgkin lymphoma (NHL) remains unclear. Here we report that both NHL patient-samples and cell lines exhibited significant up-regulation of glycolytic metabolism. The glycolytic inhibitor 2-deoxy-d-glucose (2-DG) inhibited glucose consumption, lactic acid generation and cell proliferation and induced cell cycle arrest in NHL cell lines under both normoxia and hypoxia, and hypoxia could even enhance the inhibitory effects of 2-DG. Furthermore, 2-DG combined with methylprednisolone synergistically inhibited cell proliferation, induced cell apoptosis and cell cycle arrest, and thus increased the sensitivity of NHL cells to methylprednisolone via down-regulation of HIF-1α and c-MYC. In conclusion, these results present a novel insight into critical roles of glycolytic pathway activation in NHL progression and glucocorticoid resistance. Inhibition of the glycolytic pathway may provide a new therapeutic strategy for the treatment of NHL.
Related Knowledge Centers
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