排序方式: 共有93条查询结果,搜索用时 31 毫秒
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Pau B. Esparza-Moltó Cristina Nuevo-Tapioles José M. Cuezva 《Cellular and molecular life sciences : CMLS》2017,74(12):2151-2166
The mitochondrial H+-ATP synthase is a primary hub of cellular homeostasis by providing the energy required to sustain cellular activity and regulating the production of signaling molecules that reprogram nuclear activity needed for adaption to changing cues. Herein, we summarize findings regarding the regulation of the activity of the H+-ATP synthase by its physiological inhibitor, the ATPase inhibitory factor 1 (IF1) and their functional role in cellular homeostasis. First, we outline the structure and the main molecular mechanisms that regulate the activity of the enzyme. Next, we describe the molecular biology of IF1 and summarize the regulation of IF1 expression and activity as an inhibitor of the H+-ATP synthase emphasizing the role of IF1 as a main driver of energy rewiring and cellular signaling in cancer. Findings in transgenic mice in vivo indicate that the overexpression of IF1 is sufficient to reprogram energy metabolism to an enhanced glycolysis and activate reactive oxygen species (ROS)-dependent signaling pathways that promote cell survival. These findings are placed in the context of mitohormesis, a program in which a mild mitochondrial stress triggers adaptive cytoprotective mechanisms that improve lifespan. In this regard, we emphasize the role played by the H+-ATP synthase in modulating signaling pathways that activate the mitohormetic response, namely ATP, ROS and target of rapamycin (TOR). Overall, we aim to highlight the relevant role of the H+-ATP synthase and of IF1 in cellular physiology and the need of additional studies to decipher their contributions to aging and age-related diseases. 相似文献
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Cristina Paoletti 《Studies in history and philosophy of science》2011,42(1):37-44
A neglected episode in the intellectual history of the Scottish Enlightenment, Thomas Brown’s philosophy has been recently reassessed and reconnected with the emergence of the Positivist interpretation of David Hume. In fact, aiming to defend Hume’s philosophy from the common charges of atheism and scepticism, Brown popularised an interpretation of Humean texts which was later to become the standard view on Hume. In this essay, I aim to identify Brown’s historical sources and connect his reading of Hume with the medical discussion on causality. 相似文献
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Consequences of climate change on the tree of life in Europe 总被引:2,自引:0,他引:2
Many species are projected to become vulnerable to twenty-first-century climate changes, with consequent effects on the tree of life. If losses were not randomly distributed across the tree of life, climate change could lead to a disproportionate loss of evolutionary history. Here we estimate the consequences of climate change on the phylogenetic diversities of plant, bird and mammal assemblages across Europe. Using a consensus across ensembles of forecasts for 2020, 2050 and 2080 and high-resolution phylogenetic trees, we show that species vulnerability to climate change clusters weakly across phylogenies. Such phylogenetic signal in species vulnerabilities does not lead to higher loss of evolutionary history than expected with a model of random extinctions. This is because vulnerable species have neither fewer nor closer relatives than the remaining clades. Reductions in phylogenetic diversity will be greater in southern Europe, and gains are expected in regions of high latitude or altitude. However, losses will not be offset by gains and the tree of life faces a trend towards homogenization across the continent. 相似文献
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Ricardo F. Antunes Cláudia Brandão Gonçalo Carvalho Cristina Girão Fernando A. Arosa 《Cellular and molecular life sciences : CMLS》2009,66(20):3387-3398
Red blood cells (RBC) have emerged as a novel regulatory cell type endowed with bioactivities toward activated human T cells.
Herein we show that the RBC bioactivities act on intracellular pathways initiated by T cell receptor (TCR)-dependent and -independent
stimuli, including IL-2, IL-15, and the mixture of phorbol dibutyrate and ionomycin. The RBC bioactivities preserve the antioxidant
status and are capable of rescuing activated T cells from cell death induced by serum deprivation. They are not mediated by
glycosylphosphatidylinositol-linked receptors or sialic acids, and kinetic studies revealed that they hasten the entrance
into the cell cycle. By using cyclosporine A (CsA) and rapamycin (Rapa) we show that the RBC bioactivities are calcineurin-dependent.
Thus, treatment of T cells with CsA, but not Rapa, impaired RBC bioactivities, and preincubation of RBC with CsA completely
abolished their bioactivities. We have demonstrated that RBC carry out bioactivities that are sensitive to CsA. 相似文献
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Musio A Selicorni A Focarelli ML Gervasini C Milani D Russo S Vezzoni P Larizza L 《Nature genetics》2006,38(5):528-530
Cornelia de Lange syndrome is a multisystem developmental disorder characterized by facial dysmorphisms, upper limb abnormalities, growth delay and cognitive retardation. Mutations in the NIPBL gene, a component of the cohesin complex, account for approximately half of the affected individuals. We report here that mutations in SMC1L1 (also known as SMC1), which encodes a different subunit of the cohesin complex, are responsible for CdLS in three male members of an affected family and in one sporadic case. 相似文献
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Cristina Lanni Marco Racchi Stefano Govoni 《Cellular and molecular life sciences : CMLS》2013,70(18):3327-3340
This review examines the role of drug metabolism and drug target polymorphism in determining the clinical response to antidepressants. Even though antidepressants are the most effective available treatment for depressive disorders, there is still substantial need for improvement due to the slow onset of appreciable clinical improvement and the association with side effects. Moreover, a substantial group of patients receiving antidepressant therapy does not achieve remission or fails to respond entirely. Even if the large variation in antidepressant treatment outcome across individuals remains poorly understood, one possible source of this variation in treatment outcome are genetic differences. The review focuses on a few polymorphisms which have been extensively studied, while reporting a more comprehensive reference to the existing literature in table format. It is relatively easy to predict the effect of polymorphisms in drug metabolizing enzymes, such as cytochromes P450 2D6 (CYP2D6) and cytochrome P450 2C19 (CYP2C19), which may be determined in the clinical context in order to explain or prevent serious adverse effects. The role of target polymorphism, however, is much more difficult to establish and may be more relevant for disease susceptibility and presentation rather than for response to therapy. 相似文献
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Fernando de Castro Ana Bribián Mª Cristina Ortega 《Cellular and molecular life sciences : CMLS》2013,70(22):4355-4368
Oligodendrocytes are the myelin-forming cells in the central nervous system (CNS). These cells originate from oligodendrocyte precursor cells (OPCs) during development, and they migrate extensively from oligodendrogliogenic niches along the neural tube to colonise the entire CNS. Like many other such events, this migratory process is precisely regulated by a battery of positional and signalling cues that act via their corresponding receptors and that are expressed dynamically by OPCs. Here, we will review the cellular and molecular basis of this important event during embryonic and postnatal development, and we will discuss the relevance of the substantial number of OPCs existing in the adult CNS. Similarly, we will consider the behaviour of OPCs in normal and pathological conditions, especially in animal models of demyelination and of the demyelinating disease, multiple sclerosis. The spontaneous remyelination observed after damage in demyelinating pathologies has a limited effect. Understanding the cellular and molecular mechanisms underlying the biology of OPCs, particularly adult OPCs, should help in the design of neuroregenerative strategies to combat multiple sclerosis and other demyelinating diseases. 相似文献
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Becatti M Taddei N Cecchi C Nassi N Nassi PA Fiorillo C 《Cellular and molecular life sciences : CMLS》2012,69(13):2245-2260
SIRT1, an ubiquitous NAD(+)-dependent deacetylase that plays a role in biological processes such as longevity and stress response, is significantly activated in response to reactive oxygen species (ROS) production. Resveratrol (Resv), an important activator of SIRT1, has been shown to exert major health benefits in diseases associated with oxidative stress. In ischemia-reperfusion (IR) injury, a major role has been attributed to the mitogen-activated protein kinase (MAPK) pathway, which is upregulated in response to a variety of stress stimuli, including oxidative stress. In neonatal rat ventricular cardiomyocytes subjected to simulated IR, the effect of Resv-induced SIRT1 activation and the relationships with the MAPK pathway were investigated. Resv-induced SIRT1 overexpression protected cardiomyocytes from oxidative injury, mitochondrial dysfunction, and cell death induced by IR. For the first time, we demonstrate that SIRT1 overexpression positively affects the MAPK pathway-via Akt/ASK1 signaling-by reducing p38 and JNK phosphorylation and increasing ERK phosphorylation. These results reveal a new protective mechanism elicited by Resv-induced SIRT1 activation in IR tissues and suggest novel potential therapeutic targets to manage IR-induced cardiac dysfunction. 相似文献