共查询到20条相似文献,搜索用时 640 毫秒
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Dominik C. Fuhrmann Ilka Wittig Stefan Dröse Tobias Schmid Nathalie Dehne Bernhard Brüne 《Cellular and molecular life sciences : CMLS》2018,75(16):3051-3067
Cell stress such as hypoxia elicits adaptive responses, also on the level of mitochondria, and in part is mediated by the hypoxia-inducible factor (HIF) 1α. Adaptation of mitochondria towards acute hypoxic conditions is reasonably well understood, while regulatory mechanisms, especially of respiratory chain assembly factors, under chronic hypoxia remains elusive. One of these assembly factors is transmembrane protein 126B (TMEM126B). This protein is part of the mitochondrial complex I assembly machinery. We identified changes in complex I abundance under chronic hypoxia, in association with impaired substrate-specific mitochondrial respiration. Complexome profiling of isolated mitochondria of the human leukemia monocytic cell line THP-1 revealed HIF-1α-dependent deficits in complex I assembly and mitochondrial complex I assembly complex (MCIA) abundance. Of all mitochondrial MCIA members, we proved a selective HIF-1-dependent decrease of TMEM126B under chronic hypoxia. Mechanistically, HIF-1α induces the E3-ubiquitin ligase F-box/WD repeat-containing protein 1A (β-TrCP1), which in turn facilitates the proteolytic degradation of TMEM126B. Attenuating a functional complex I assembly appears critical for cellular adaptation towards chronic hypoxia and is linked to destruction of the mitochondrial assembly factor TMEM126B. 相似文献
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The role of hypoxia-inducible factors in cancer 总被引:7,自引:0,他引:7
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Studies of O2 supply in freshly isolated adult mammalian cells provide new insight into the factors that limit mitochondrial oxygenation in vivo. Of particular importance, mitochondria are present at high densities and often in apparent clusters, both of which contribute to local O2 gradients under hypoxic conditions. Current evidence indicates that the mitochondrial distribution is a component of the differentiated phenotype of adult mammalian cells and that specific motors and anchoring mechanisms are present to allow redistribution in response to developmental, physiological and pathological challenges. To compare the importance of resistance to O2 transfer under different conditions and at different sites along the supply path in vivo, a simple mathematical expression of relative resistance to O2 supply is introduced. Under various pathophysiological conditions, this resistance increases in specific regions of the pulmonary, circulatory or cellular supply path and results in O2 deficiency in the mitochondria. Regardless of cause, the relative resistance increases dramatically in the vicinity of mitochondrial clusters during hypoxia. 相似文献
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Regulation of transcription factor function by phosphorylation 总被引:1,自引:1,他引:0
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Vincent Joseph Jean-Marc Pequignot 《Cellular and molecular life sciences : CMLS》2009,66(22):3565-3573
Acclimatization to long-term hypoxia takes place at high altitude and allows gradual improvement of the ability to tolerate
the hypoxic environment. An important component of this process is the hypoxic ventilatory acclimatization (HVA) that develops
over several days. HVA reveals profound cellular and neurochemical re-organization occurring both in the peripheral chemoreceptors
and in the central nervous system (in brainstem respiratory groups). These changes lead to an enhanced activity of peripheral
chemoreceptor and re-inforce the central translation of peripheral inputs to efficient respiratory motor activity under the
steady low O2 pressure. We will review the cellular processes underlying these changes with a particular emphasis on changes of neurotransmitter
function and ion channel properties in peripheral chemoreceptors, and present evidence that low O2 level acts directly on brainstem nuclei to induce cellular changes contributing to maintain a high tonic respiratory drive
under chronic hypoxia. (This study is part of a multi-author review.) 相似文献
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Mammalian target of rapamycin (mTOR) is a protein serine/threonine kinase that controls a wide range of growth-related cellular
processes. In the past several years, many factors have been identified that are involved in controlling mTOR activity. Those
factors in turn are regulated by diverse signaling cascades responsive to changes in intracellular and environmental conditions.
The molecular connections between mTOR and its regulators form a complex signaling network that governs cellular metabolism,
growth and proliferation. In this review, we discuss some key factors in mTOR regulation and mechanisms by which these factors
control mTOR activity. 相似文献
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The stress-activated protein kinase pathways 总被引:29,自引:0,他引:29
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Marten Szibor Jochen Pöling Henning Warnecke Thomas Kubin Thomas Braun 《Cellular and molecular life sciences : CMLS》2014,71(10):1907-1916
Cardiomyocytes continuously generate the contractile force to circulate blood through the body. Imbalances in contractile performance or energy supply cause adaptive responses of the heart resulting in adverse rearrangement of regular structures, which in turn might lead to heart failure. At the cellular level, cardiomyocyte remodeling includes (1) restructuring of the contractile apparatus; (2) rearrangement of the cytoskeleton; and (3) changes in energy metabolism. Dedifferentiation represents a key feature of cardiomyocyte remodeling. It is characterized by reciprocal changes in the expression pattern of “mature” and “immature” cardiomyocyte-specific genes. Dedifferentiation may enable cardiomyocytes to cope with hypoxic stress by disassembly of the energy demanding contractile machinery and by reduction of the cellular energy demand. Dedifferentiation during myocardial repair might provide cardiomyocytes with additional plasticity, enabling survival under hypoxic conditions and increasing the propensity to enter the cell cycle. Although dedifferentiation of cardiomyocytes has been described during tissue regeneration in zebrafish and newts, little is known about corresponding mechanisms and regulatory circuits in mammals. The recent finding that the cytokine oncostatin M (OSM) is pivotal for cardiomyocyte dedifferentiation and exerts strong protective effects during myocardial infarction highlights the role of cytokines as potent stimulators of cardiac remodeling. Here, we summarize the current knowledge about transient dedifferentiation of cardiomyocytes in the context of myocardial remodeling, and propose a model for the role of OSM in this process. 相似文献
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K. von Schwarzenberg S. A. E. Held A. Schaub K. M. Brauer A. Bringmann P. Brossart 《Cellular and molecular life sciences : CMLS》2009,66(7):1295-1308
In order to analyze the effects of peroxisome proliferator-activated receptor-γ (PPARγ) activation on renal cell carcinomas
we utilized several cell lines that were treated with the high affinity PPARγ agonist, troglitazone. Incubation of RCC cells
with troglitazone resulted in reduced secretion of growth factors that was due to the inhibition of MAP kinase signaling and
reduced nuclear localized expression of relB and HIF1alpha. Interestingly, the cell lines used showed a different sensitivity
towards apoptosis induction that did not correlate with the inhibition of growth factors or expression of pro- and antiapoptotic
molecules. To overcome this resistance the cells were treated with a combination of troglitazone and the proteasome inhibitor,
bortezomib. The combination of both compounds induced apoptosis even in cells resistant to both agents alone, due to increased
induction of ER-stress and caspase-3 mediated cell death.
Received 03 September 2009; received after revision 02 February 2009; accepted 10 February 2009 相似文献
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E. Christians E. Michel J.-P. Renard 《Cellular and molecular life sciences : CMLS》1997,53(2):168-176
Heat shock genes are found in all organisms, and synthesis of heat shock proteins is induced by various stressors in nearly
all the cells forming these organisms. However, a particular situation is noticed for hsp70 genes in mouse embryos at the beginning of their development. First, spontaneous expression of hsp70 is observed at the onset of zygotic genome activity. Second, inducible expression is delayed until morula or early blastocyst
stages. A better understanding of both these points depends on a more careful analysis of hsp70 expression in relation to their major regulators, the heat shock factors. In this review, we will see how the development
of the preimplanta tion embryo highlights the complexity of heat shock gene regulation involving trans-cis interactions and the cellular and nuclear environment. 相似文献