Enhanced Glycolytic Metabolism Contributes to Cardiac Dysfunction in Polymicrobial Sepsis

Zheng, Zhibo; Ma, He; Zhang, Xia; Tu, Fei; Wang, Xiaohui; Ha, Tuanzhu; Fan, Min; Liu, Li; Xu, Jingjing; Yu, Kaijiang; Wang, Ruitao; Kalbfleisch, John H.; Kao, Race L.; Williams, David L.; Li, Chuanfu

doi:10.1093/infdis/jix138

Cited by 117 publications

(112 citation statements)

References 42 publications

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“…In T cells, blocking glycolysis with 2-DG leads to a differentiation of Th17 cells into Treg cells (Shi et al, 2011). In vivo, 2-DG significantly improves survival in both the LPS (Wang et al, 2016) and CLP (Zheng et al, 2017) model of sepsis by downregulating lactate and inflammatory cytokine production. In contrast, 2-DG conferred no protection in a poly(I:C)-induced systemic inflammation model (Wang et al, 2016).…”

Section: Hyperglycemiamentioning

confidence: 99%

Reprogramming of basic metabolic pathways in microbial sepsis: therapeutic targets at last?

2018

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Sepsis is a highly lethal and urgent unmet medical need. It is the result of a complex interplay of several pathways, including inflammation, immune activation, hypoxia, and metabolic reprogramming. Specifically, the regulation and the impact of the latter have become better understood in which the highly catabolic status during sepsis and its similarity with starvation responses appear to be essential in the poor prognosis in sepsis. It seems logical that new interventions based on the recognition of new therapeutic targets in the key metabolic pathways should be developed and may have a good chance to penetrate to the bedside. In this review, we concentrate on the pathological changes in metabolism, observed during sepsis, and the presumed underlying mechanisms, with a focus on the level of the organism and the interplay between different organ systems.

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Section: Hyperglycemiamentioning

confidence: 99%

Reprogramming of basic metabolic pathways in microbial sepsis: therapeutic targets at last?

2018

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“…Repression of SIRT3 expression by RIP140 is dependent on ERRα [101]. A hexokinase inhibitor, 2-deoxy-d-glucose, administration significantly improves cardiac function and reduces myocardial apoptosis [102]. Zhen et al pointed out that upregulation of SIRT3 expression along with SIRT1 by this agent might be important contributors to its protective action against septic cardiomyopathy [102].…”

Section: Changes In Sirtuin 3 Expression In Carcinogenesismentioning

confidence: 99%

“…A hexokinase inhibitor, 2-deoxy-d-glucose, administration significantly improves cardiac function and reduces myocardial apoptosis [102]. Zhen et al pointed out that upregulation of SIRT3 expression along with SIRT1 by this agent might be important contributors to its protective action against septic cardiomyopathy [102]. Stimulation of SIRT3 expression improves the mitochondrial respiratory function and improves the cardiac function of mice.…”

Section: Changes In Sirtuin 3 Expression In Carcinogenesismentioning

confidence: 99%

“…Metformin, which is a drug used for the treatment of diabetes, upregulates the expression of SIRT3 in about 8 weeks old mice with heart failure after myocardial infarction [103]. It was suggested that metformin-mediated SIRT3 upregulation and deacetylation of PGC-1α increase mitochondrial ATP production and mitochondrial oxygen consumption rates in the [24,102] Metformin N/A PGC-1α Stimulates mitochondrial ATP production and oxygen consumption rates [103] Adjudin N/A IDH2 Scavenges mtROS [96,97] RIP140 (SIRT3 repressing TF) ERRα LCAD Increases mtROS and lipid accumulation [92,101] MnSOD: manganese superoxide dismutase; IDH2: isocitrate dehydrogenase; Forkhead box O 3a (FOXO3a); LCAD: longchain acyl-CoA dehydrogenase; AMPK: AMP-activated protein kinase; GSH-Px: glutathione peroxidase; PGC-1α: peroxisome proliferator-activated receptor gamma coactivator 1-alpha; ERRα: estrogen-related receptor alpha; NRF1: nuclear respiratory factor 1; TFAM: transcription factor A, mitochondrial; OGG1: 8-oxoguanine glycosylase; MFN-1: mitofusin-1; OPA1: dynamin-like 120 kDa protein; Ku70; ATP-dependent DNA helicase II, 70 kDa subunit; BCL-2: B-cell lymphoma 2; NF-κB: nuclear factor kappa-light-chain enhancer of activated B cells; TF: transcription factor. Gene Expression and Regulation in Mammalian Cells -Transcription Toward the Establishment of Novel Therapeuticsmouse hearts of myocardial infarction and decrease the associated damage [103].…”

Section: Changes In Sirtuin 3 Expression In Carcinogenesismentioning

confidence: 99%

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Changes in the Expression and the Role of Sirtuin 3 in Cancer Cells and in Cardiovascular Health and Disease

Özden¹,

Tural²

2018

Gene Expression and Regulation in Mammalian Cells - Transcription Toward the Establishment of Novel Therapeutics

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Sirtuin 3, an NAD + -dependent deacetylase, whose expression is considered a marker in life extension, is downregulated with age and in various diseases. Sirtuin 3 is predominantly localized to the mitochondria and considered a fidelity protein for the integrity and function of this organelle. Some studies report its localization in the nucleus to regulate the expression of stress response-related genes and that reduced expression of SIRT3 produces a cellular milieu permissive for human pathologies. Since the expression and activity of Sirtuin 3 are important for the regulation of antioxidant defense, metabolism, and apoptosis initiation, the expression of SIRT3 is also important in the context of ageassociated illnesses. A variety of small molecules are being developed to modulate the expression or activity of Sirtuin 3 and are potentially a valuable strategy to change mitochondrial acetylome to treat several diseases. The AMPK-PGC1α-SIRT3 axis plays a critical role in preserving mitochondrial biogenesis and function. Here, we summarize how changes in Sirtuin 3 expression are regulated in cancer and dysfunctions in cardiovascular diseases. The potential therapeutic strategies by targeting Sirtuin 3 expression to improve mitochondrial function in cancer and cardiovascular diseases are summarized.

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“…Nas análises de correlação foram encontrados valores significativos nos grupos com 1,5 e 3,0 mg/Kg -LPS (Gráfico 10) demonstrando que quanto maior a concentração do lactato maior a temperatura corporal. Estudos recentes mostram que a diminuição na produção de lactato resultou na melhora da sobrevida de animais (ZHENG et al, 2017;XIE et al, 2016;YANG et al, 2014).…”

Section: Correlação Entre As Concentrações De Lactato Plasmático Eunclassified

Efeito da endotoxemia na temperatura corporal, pressão arterial média e nas concentrações de nitrato e lactato plasmáticos em ratos

Souza¹

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AGRADECIMENTOSÁ Deus, por conhecer cada detalhe da minha vida e proporcionar condições para que eu pudesse realizar todos os meus sonhos. Obrigado por colocar tantas pessoas boas no meu caminho e permitir com que eu possa seguir em frente. Á todos os amigos e colegas que proporcionaram momentos inesquecíveis no decorrer da vida e que de alguma forma contribuíram para que eu me tornasse a pessoa que sou hoje.Ás minhas orientadoras acadêmicas que me mostraram o caminho para chegar até aqui, obrigado pelo acolhimento, pelo incentivo e pela oportunidade em aprender com vocês, Dra. Evelise Aline Soares, Dra. Denise Holanda Iunes e Dra. Evelin Capellari Cárnio. Á Dra. Evelin Capellari Cárnio pelo exemplo de pessoa, pesquisadora e principalmente pelo Ser Humano que é. Obrigado por tornar essa trajetória leve e repleta de aprendizados.Ao Marcelo Eduardo Batalhão, pelo apoio em todas as etapas deste trabalho, pelas horas de conversa e boas risadas.Aos meus colegas de laboratório Angelita, Felipe, Patrícia e Aline pelos momentos de descontração e aprendizado.Aos meus amigos Juliano Caliari e Bárbara Sousa, obrigado por cada momento vivido até aqui.Ás Faculdades Integradas do Vale do Ribeira, em especial a Deise Aparecida Carminatte por acreditar no meu trabalho e proporcionar condições para a realização desta etapa.Aos meus amigos de Registro-SP Patrícia Santiago e José Simas por estarem presentes nos momentos tristes e felizes.A todos os meus amigos de Alfenas-MG, que mesmo distantes, se fazem presentes na memória e nas oportunidades de encontro. Á Escola de Enfermagem de Ribeirão pela oportunidade de crescimento profissional e possibilidade em cursar o doutorado. RESUMO SOUZA, A. L. T. Efeito da endotoxemia na temperatura corporal, pressão arterial média e nas concentrações de nitrato e lactato plasmáticos em ratos. 2019. 81f. Tese (Doutorado em Ciências) -Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, 2019.Na endotoxemia e na sepse alterações nos sinais vitais e em biomarcadores estão presentes e sinalizam o grau de comprometimento fisiológico. Embora a interpretação sobre as concentrações do óxido nítrico (NO) e do lactato plasmáticos na pressão arterial sejam bem estabelecidas na literatura, elucidações sobre suas participações na temperatura corporal ainda são incipientes. Assim, este estudo teve como objetivo avaliar o efeito da endotoxemia na temperatura corporal, pressão arterial média e correlacionar esses valores com os biomarcadores NO e lactato plasmáticos. Foram utilizados 40 ratos divididos igualmente em cinco grupos experimentais. A indução da endotoxemia foi realizada por meio da administração endovenosa de lipopolissacarídeo (LPS) bacteriano, respectivamente 0,5 mg/Kg, 1,5 mg/Kg, 3,0 mg/Kg e 10 mg/Kg. O grupo controle recebeu 0,5 mL de solução salina. O experimento teve duração de seis horas. Na 0h (medida basal) foram coletadas amostras de sangue (0,4 mL) para dosagem do NO e lactato plasmáticos e obtidos os valores de temperatura corporal e pressão arterial média, na ...

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Enhanced Glycolytic Metabolism Contributes to Cardiac Dysfunction in Polymicrobial Sepsis

Abstract: Glycolytic metabolism plays an important role in mediating sepsis-induced septic cardiomyopathy. The mechanisms may involve regulation of inflammatory response and apoptotic signaling.

Cited by 117 publications

References 42 publications

Reprogramming of basic metabolic pathways in microbial sepsis: therapeutic targets at last?

Reprogramming of basic metabolic pathways in microbial sepsis: therapeutic targets at last?

Changes in the Expression and the Role of Sirtuin 3 in Cancer Cells and in Cardiovascular Health and Disease

Efeito da endotoxemia na temperatura corporal, pressão arterial média e nas concentrações de nitrato e lactato plasmáticos em ratos

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