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71.
G. M. C. Janssen P. Schwertman T. A. T. Wanga R. S. Jahangir Tafrechi P. J. A. van den Broek A. K. Raap 《Cellular and molecular life sciences : CMLS》2009,66(4):721-730
Cytoplasmic translation is under sophisticated control but how cells adapt its rate to constitutive loss of mitochondrial
oxidative phosphorylation is unknown. Here we show that translation is repressed in cells with the pathogenic A3243G mtDNA
mutation or in mtDNA-less ρ0 cells by at least two distinct pathways, one transiently targeting elongation factor eEF-2 and the other initiation factor
eIF-2α constitutively. Under conditions of exponential cell growth and mammalian target of rapamycin (mTOR) activation, eEF-2
becomes transiently phosphorylated by an AMP-activated protein kinase (AMPK)-dependent pathway, especially high in mutant
cells. Independent of AMPK and mTOR, eIF-2α is constitutively phosphorylated in mutant cells, likely a signature of endoplasmic
reticulum (ER)-stress response induced by the loss of oxidative phosphorylation. While the AMPK/eEF-2K/eEF-2 pathway appears
to function in adaptation to physiological fluctuations in ATP levels in the mutant cells, the ER stress signified by constitutive
protein synthesis inhibition through eIF-2α-mediated repression of translation initiation may have pathobiochemical consequences.
Received 29 October 2008; received after revision 11 December 2008; accepted 16 December 2008 相似文献
72.
Functions and pathologies of BiP and its interaction partners 总被引:1,自引:1,他引:0
J. Dudek J. Benedix S. Cappel M. Greiner C. Jalal L. Müller R. Zimmermann 《Cellular and molecular life sciences : CMLS》2009,66(9):1556-1569
The endoplasmic reticulum (ER) is involved in a variety of essential and interconnected processes in human cells, including
protein biogenesis, signal transduction, and calcium homeostasis. The central player in all these processes is the ER-lumenal
polypeptide chain binding protein BiP that acts as a molecular chaperone. BiP belongs to the heat shock protein 70 (Hsp70)
family and crucially depends on a number of interaction partners, including co-chaperones, nucleotide exchange factors, and
signaling molecules. In the course of the last five years, several diseases have been linked to BiP and its interaction partners,
such as a group of infectious diseases that are caused by Shigella toxin producing E. coli. Furthermore, the inherited diseases Marinesco-Sj?gren syndrome, autosomal dominant polycystic liver disease, Wolcott-Rallison
syndrome, and several cancer types can be considered BiP-related diseases. This review summarizes the physiological and pathophysiological
characteristics of BiP and its interaction partners.
Received 20 November 2008; received after revision 09 December 2008; accepted 12 December 2008 相似文献
73.
S. Kjellev 《Cellular and molecular life sciences : CMLS》2009,66(8):1350-1369
The trefoil factor family (TFF) comprises a group of small peptides which are highly expressed in tissues containing mucus-producing
cells – especially in the mucosa lining the gastrointestinal tract. The peptides seem crucial for epithelial restitution and
may work via other pathways than the conventional factors involved in restitution. In vitro studies have shown that the TFFs promote restitution using multiple mechanisms. The peptides also have other functionalities
including interactions with the immune system. Moreover, therapeutic effects of the TFFs have been shown in several animal
models of gastrointestinal damage. Still it is not clear which of their in vitro properties are involved in the in vivo mode of action. This review describes the TFF family with emphasis on their biological properties and involvement in mucosal
protection and repair.
Received 10 October 2008; received after revision 07 November 2008; accepted 10 November 2008 相似文献
74.
目的研究血清碱性磷酸酶检测临床肝疾病时的方法学,提高临床诊断价值。方法收集临床不同肝疾病病人的血清,分别用3种方法测定其碱性磷酸酶的活性,并与健康对照组比较作诊断性能分析。结果各肝疾病组血清碱性磷酸酶的活性与对照组相比有极显著差异(P〈0.001);3种方法分别测定各组之闻的血清碱性磷酸酶活性无显著性差异(P〉0.05)。2.乙基氨基乙醇、2-氨基-2-甲基-1-丙醇、二乙醇胺3种缓冲液测定试剂盒方法测定的灵敏度分别为55.20%、47.96%、51.13%,特异度分别为100%、100%、93.75%。结论血清碱性磷酸酶可以作为各类肝病的临床诊断指标;对肝疾病血清碱性磷酸酶测定用2,乙基氨基乙醇缓冲液的试剂方法测定效果较好。 相似文献
75.
Shin JM Vagin O Munson K Kidd M Modlin IM Sachs G 《Cellular and molecular life sciences : CMLS》2008,65(2):264-281
Inhibition of gastric acid secretion is the mainstay of the treatment of gastroesophageal reflux disease and peptic ulceration;
therapies to inhibit acid are among the best-selling drugs worldwide. Highly effective agents targeting the histamine H2 receptor
were first identified in the 1970s. These were followed by the development of irreversible inhibitors of the parietal cell
hydrogen-potassium ATPase (the proton pump inhibitors) that inhibit acid secretion much more effectively. Reviewed here are
the chemistry, biological targets and pharmacology of these drugs, with reference to their current and evolving clinical utilities.
Future directions in the development of acid inhibitory drugs include modifications of current agents and the emergence of
a novel class of agents, the acid pump antagonists.
Received 30 May 2007; received after revision 15 August 2007; accepted 13 September 2007 相似文献
76.
A STAGE-STRUCTURED SI ECO-EPIDEMIOLOGICAL MODEL WITH TIME DELAY AND IMPULSIVE CONTROLLING* 总被引:1,自引:0,他引:1
This paper formulates a robust stage-structured SI eco-epidemiological model with periodic constant pulse releasing of infectious pests with pathogens. The authors show that the conditions for global attractivity of the 'pest-eradication' periodic solution and permanence of the system depend on time delay, hence, the authors call it "profitless". Further, the authors present a pest management strategy in which the pest population is kept under the economic threshold level (ETL) when the pest population is uniformly persistent. By numerical analysis, the authors also show that constant maturation time delay for the susceptible pests and pulse releasing of the infectious pests can bring obvious effects on the dynamics of system. 相似文献
77.
Many notions regarding the function, structure and regulation of cholera toxin expression have remained essentially unaltered
in the last 15 years. At the same time, recent findings have generated additional perspectives. For example, the cholera toxin
genes are now known to be carried by a non-lytic bacteriophage, a previously unsuspected condition. Understanding of how the
expression of cholera toxin genes is controlled by the bacterium at the molecular level has advanced significantly and relationships
with cell-density-associated (quorum-sensing) responses have recently been discovered. Regarding the cell intoxication process,
the mode of entry and intracellular transport of cholera toxin are becoming clearer. In the immunological field, the strong
oral immunogenicity of the non-toxic B subunit of cholera toxin (CTB) has been exploited in the development of a now widely
licensed oral cholera vaccine. Additionally, CTB has been shown to induce tolerance against co-administered (linked) foreign
antigens in some autoimmune and allergic diseases.
Received 25 October 2007; accepted 12 December 2007 相似文献
78.
Taylor DM Maxwell MM Luthi-Carter R Kazantsev AG 《Cellular and molecular life sciences : CMLS》2008,65(24):4000-4018
Sirtuins comprise a unique class of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that target multiple protein substrates to execute diverse biological functions. These enzymes are
key regulators of clinically important cellular and organismal processes, including metabolism, cell division and aging. The
desire to understand the important determinants of human health and lifespan has resulted in a firestorm of work on the seven
mammalian sirtuins in less than a decade. The implication of sirtuins in medically important areas such as diabetes, cancer,
cardiovascular dysfunction and neurodegenerative disease has further catapulted them to a prominent status as potential targets
for nutritional and therapeutic development. Here, we present a review of published results on sirtuin biology and its relevance
to human disease.
Received 25 June 2008; received after revision 20 August 2008; accepted 29 August 2008 相似文献
79.
Muñoz U Bartolomé F Esteras N Bermejo-Pareja F Martín-Requero A 《Cellular and molecular life sciences : CMLS》2008,65(21):3507-3519
It has been proposed that neuroinflammation, among other factors, may trigger an aberrant neuronal cell cycle re-entry leading
to neuronal death. Cell cycle disturbances are also detectable in peripheral cells from Alzheimer’s disease (AD) patients.
We previously reported that the anti-inflammatory 15- deoxy-Δ12,14-prostaglandin J
2 (15d-PGJ
2) increased the cellular content of the cyclin-dependent kinase inhibitor p27, in lymphoblasts from AD patients. This work
aimed at elucidating the mechanisms of 15d-PGJ
2-induced p27 accumulation. Phosphorylation, half-life, and the nucleo-cytoplasmic traffic of p27 protein were altered by 15d-PGJ2
by mechanisms dependent on PI3K/Akt activity. 15d-PGJ
2 prevents the calmodulin-dependent Akt overactivation in AD lymphoblasts by blocking its binding to the 85-kDa regulatory
subunit of PI3K. These effects of 15d-PGJ
2 were not mimicked by 9,10-dihydro-15-deoxy-Δ12,14- prostaglandin J
2, suggesting that 15d-PGJ
2 acts independently of peroxisome proliferator-activated receptor γ activation and that the α,β-unsaturated carbonyl group
in the cyclopentenone ring of 15d-PGJ
2 is a requisite for the observed effects.
Received 14 July 2008; received after revision 2 September 2008; accepted 12 September 2008 相似文献
80.
Liver X receptors in cardiovascular and metabolic disease 总被引:5,自引:0,他引:5
Liver X receptors (LXRs) α and β are nuclear oxysterol receptors and metabolic sensors initially found to regulate cholesterol
metabolism and lipid biosynthesis. Recent studies have elucidated the importance of LXR in the development of cardiovascular
diseases and metabolic disorders. LXR agonists prevent development of atherosclerosis by modulation of metabolic as well as
inflammatory gene expression in rodent models. Moreover, LXR activation inhibits hepatic gluconeogenesis and lowers serum
glucose levels, indicating possible application of LXR activation in the treatment of diabetes mellitus. However, first-generation
LXR agonists elevate hepatic and serum trigylceride levels, making subtype-specific agonists and selective LXR modulators
rather than unselective LXR agonists a potential pharmacological strategy. This review summarizes the multiple physiological
and pathophysiological implications of LXRs and observations that identify LXRs as potential targets for therapeutic interventions
in human cardiovascular and metabolic disease.
Received 30 August 2005; received after revision 10 October 2005; accepted 4 November 2005 相似文献