共查询到10条相似文献,搜索用时 15 毫秒
1.
P. C. Newell D. Malchow J. D. Gross 《Cellular and molecular life sciences : CMLS》1995,51(12):1155-1165
Changes in cytosolic Ca2+ play an important role in a wide array of cell types and the control of its concentration depends upon the interplay of many cellular constituents. Resting cells maintain cytosolic calcium ([Ca2+]i) at a low level in the face of steep gradients of extracellular and sequestered Ca2+. Many different signals can provoke the opening of calcium channels in the plasma membrane or in intracellular compartments and cause rapid influx of Ca2+ into the cytosol and elevation of [Ca2+]i. After such stimulation Ca2+ ATPases located in the plasma membrane and in the membranes of intracellular stores rapidly return [Ca2+]i to its basal level. Such responses to elevation of [Ca2+]i are a part of an important signal transduction mechanism that uses calcium (often via the binding protein calmodulin) to mediate a variety of cellular actions responsive to outside influences. 相似文献
2.
Alternative splicing of Bcl-2-related genes: functional consequences and potential therapeutic applications 总被引:6,自引:0,他引:6
Apoptosis is a morphologically distinct form of cell death. It is executed and regulated by several groups of proteins. Bcl-2 family proteins are the main regulators of the apoptotic process acting either to inhibit or promote it. More than 20 members of the family have been identified so far and most have two or more isoforms. Alternative splicing is one of the major mechanisms providing proteomic complexity and functional diversification of the Bcl-2 family proteins. Pro- and anti-apoptotic Bcl-2 family members should function in harmony for the regulation of the apoptosis machinery, and their relative levels are critical for cell fate. Any mechanism breaking down this harmony by changing the relative levels of these antagonistic proteins could contribute to many diseases, including cancer and neurodegenerative disorders. Recent studies have shown that manipulation of the alternative splicing mechanisms could provide an opportunity to restore the proper balance of these regulator proteins. This review summarises current knowledge on the alternative splicing products of Bcl-2-related genes and modulation of splicing mechanisms as a potential therapeutic approach.Received 5 January 2004; received after revision 31 March 2004; accepted 6 April 2004 相似文献
3.
R. Brückner S. Gramann M. Nose W. Schmitz H. Scholz 《Cellular and molecular life sciences : CMLS》1985,41(6):732-734
Summary The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) mimicked the effects of isoprenaline on the force of contraction, the cAMP content and the slow Ca++ inward current (Isi) in isolated guinea pig papillary muscles. The results support the hypothesis that phosphodiesterase inhibitors and -adrenoceptor agonists exert their positive inotropic effects by increasing Isi via the common mediator cAMP.Acknowledgment. This work was supported by the Deutsche Forschungsgemeinschaft. 相似文献
4.
The RecQ family of DNA helicases is highly conserved throughout evolution and plays an important role in the maintenance of
genomic stability in all organisms. Mutations in three of the five known family members in humans, BLM, WRN and RECQL4, give rise to disorders that are characterized by predisposition to cancer and premature aging, emphasizing the importance
of studying the RecQ proteins and their cellular activities. Interestingly, three autosomal recessive disorders have been
associated with mutations in the RECQL4 gene: Rothmund-Thomson, RAPADILINO, and Baller-Gerold syndromes, thus making RECQL4 unique within the RecQ family of DNA
helicases. To date, however, the molecular function of RECQL4 and the possible cellular pathways in which it is involved remain
poorly understood. Here, we present an overview of recent findings in connection with RECQL4 and try to highlight different
directions the field could head, helping to clarify the role of RECQL4 in preventing tumorigenesis and maintenance of genome
integrity in humans.
Received 31 October 2006; received after revision 4 January 2007; accepted 5 February 2007 相似文献
5.
T-cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays 总被引:1,自引:1,他引:0
Stefan F. Martin Philipp R. Esser Sonja Schmucker Lisa Dietz Dean J. Naisbitt B. Kevin Park Marc Vocanson Jean-Francois Nicolas Monika Keller Werner J. Pichler Matthias Peiser Andreas Luch Reinhard Wanner Enrico Maggi Andrea Cavani Thomas Rustemeyer Anne Richter Hermann-Josef Thierse Federica Sallusto 《Cellular and molecular life sciences : CMLS》2010,67(24):4171-4184
Chemicals can elicit T-cell-mediated diseases such as allergic contact dermatitis and adverse drug reactions. Therefore, testing of chemicals, drugs and protein allergens for hazard identification and risk assessment is essential in regulatory toxicology. The seventh amendment of the EU Cosmetics Directive now prohibits the testing of cosmetic ingredients in mice, guinea pigs and other animal species to assess their sensitizing potential. In addition, the EU Chemicals Directive REACh requires the retesting of more than 30,000 chemicals for different toxicological endpoints, including sensitization, requiring vast numbers of animals. Therefore, alternative methods are urgently needed to eventually replace animal testing. Here, we summarize the outcome of an expert meeting in Rome on 7 November 2009 on the development of T-cell-based in vitro assays as tools in immunotoxicology to identify hazardous chemicals and drugs. In addition, we provide an overview of the development of the field over the last two decades. 相似文献
6.
K. Kumari P. S. R. Murthy M. K. Sahib 《Cellular and molecular life sciences : CMLS》1991,47(3):252-254
Summary Monoaminoguanidine administration (25 mg/kg b.wt, i.p. for 14 weeks) to alloxan diabetic rats (blood glucose 250 mg/dl) decreased the nonenzymatic protein glycosylation and sorbitol levels. It prevented development of Armanni-Ebstein tubular lesions, pathological changes in the glomerular capillary tufts and glomerular basement membrane thickening in the kidney.CDRI Communication no. 4694. 相似文献
7.
Expansion of amino acid homo-sequences, such as polyglutamines or polyalanines, in proteins has been directly implicated in
various degenerative diseases through a mechanism of protein misfolding and aggregation. However, it is still unclear how
the nature of the expansion and the protein context influence the tendency of a protein to aggregate. Here, we have addressed
these questions using spinocerebellar ataxia type-3 (ATX3) protein, the best characterised of the polyglutamine proteins,
chosen as a model system. Using a transfected mammalian cell line, we demonstrate that ATX3 aggregation is noticeably reduced
by deletion or replacement of regions other than the polyglutamine tract. The nature of the amino acid homo-sequences also
has a strong influence on aggregation. From our studies, we draw general conclusions on the effect of the protein architecture
and of the amino acid homo-sequence on pathology.
Received 3 March 2006; received after revision 19 April 2006; accepted 22 May 2006 相似文献
8.
During the last decade we have learned much on physiological changes in the secretion of the pineal hormone melatonin (MLT) in man. Reportedly, there is little or no MLT secreted before age 3 months. Then MLT production commences, becmes circadian, and reaches highest nocturnal levels at the age of 1–3 years. During all of childhood nocturnal peak levles drop progressively by 80% until adult levels are reached. This alteration appears to be the consequence of increasing body size in face of constant MLT production during childhood. The biological significance of this MLT alteration is presently unknown. Because of conceptual considerations, major depressive syndrome (MDS) and seasonal affective disorder (SAD) have been in the focus of pineal research for several years. Although in these disorders alterations in MLT levels could not be substantiated, light therapy, a consequence of this research, was discovered as an effective treatment for SAD and perhaps for MDS. In addition, there is some recent evidence for low MLT levels in schizophrenia. Finally, the potential effect of MLT in neuroimmunoendocrine interactions is presently explored. Reportedly, in vitro studies and animal experiments give evidence for a modulatory role of MLT in the immune response. However, the exact way of this possible action of MLT remains to be clarified. Clinical studies are too scant for a meaningful estimation of MLT's involvement in human neuroimmunoendocrine interactions. 相似文献
9.
M. Hiramoto Y. Fujimoto K. Kakinuma N. Ikekawa E. Ohnishi 《Cellular and molecular life sciences : CMLS》1988,44(7):623-625
Summary Two novel ecdysteroid conjugates, 2,22-dideoxy-20-hydroxyecdysone 3-phosphate (1) and bombycosterol 3-phosphate (2), as well as four known ecdysteroid 22-phosphate esters, have been isolated and characterized from the ovaries of the silkworm,Bombyx mori. 相似文献
10.
Summary In the rat endometrium, resident macrophages and exudate phagocytes ensure proteolysis by means of phagocytosis, macro-and micropinocytosis. Using exogenous tracer particles no ultrastructural evidence could be obtained for the occurrence of endometrial prelymphatics. It is suggested that the free tissue fluid may be drained via the fenestrated (probably venous) blood capillaries.Supported by a grant from the Nationaal Fonds voor Wetenschappelijk Onderzoek-Fonds voor Geneeskundig Wetenschappelijk Onderzoek (Belgium). 相似文献