共查询到20条相似文献,搜索用时 10 毫秒
1.
Dynamic protein methylation in chromatin biology 总被引:1,自引:1,他引:0
2.
Role of full-length osteoprotegerin in tumor cell biology 总被引:1,自引:1,他引:0
G. Zauli E. Melloni S. Capitani P. Secchiero 《Cellular and molecular life sciences : CMLS》2009,66(5):841-851
Osteoprotegerin (OPG) is a soluble tumor necrosis factor receptor family member, which potently inhibits RANKL-mediated osteoclastogenesis.
Numerous constructs have been created for therapeutic purposes in which the heparin-binding and death homology domains of
OPG were removed and the remaining peptide (amino acids 22–194) was fused to the Fc domain of human IgG1 (OPG-Fc). The administration
of OPG-Fc efficiently counteracted bone loss in a variety of preclinical models of cancers. However, several in vitro studies have shown that native or recombinant full-length OPG not only neuralizes RANKL, but also the death-inducing ligand
TRAIL, suggesting that OPG might potentially counteract the anti-tumor activity of TRAIL. Additional evidence suggests that
full-length OPG possesses RANKL- and TRAIL-independent biological properties, mainly related to the promotion of endothelial
cell survival and angiogenesis. Finally, breast tumor cells overexpressing OPG have shown increased bone metastatic potential
in vivo. The relevance of these apparently conflicting findings in tumor cell biology is highlighted.
Received 2 September 2008; received after revision 29 September 2008; accepted 13 October 2008 相似文献
3.
Monocytes and their pathophysiological role in Crohn’s disease 总被引:1,自引:1,他引:0
Zhou L Braat H Faber KN Dijkstra G Peppelenbosch MP 《Cellular and molecular life sciences : CMLS》2009,66(2):192-202
Our immune system shows a stringent dichotomy, on the one hand displaying tolerance towards commensal bacteria, but on the
other hand vigorously combating pathogens. Under normal conditions the balance between flora tolerance and active immunity
is maintained via a plethora of dynamic feedback mechanisms. If, however, the balancing act goes faulty, an inappropriate
immune reaction towards an otherwise harmless intestinal flora causes disease, Crohn’s disease for example. Recent developments
in the immunology and genetics of mucosal diseases suggest that monocytes and their derivative cells play an important role
in the pathophysiology of Crohn’s disease. In our review, we summarize the recent studies to discuss the dual function of
monocytes - on the one hand the impaired monocyte function initiating Crohn’s disease, and on the other hand the overactivation
of monocytes and adaptive immunity maintaining the disease. With a view to developing new therapies, both aspects of monocyte
functions need to be taken into account.
Received 1 June 2008; received after revision 24 July 2008; accepted 13 August 2008 相似文献
4.
Aerts AM François IE Cammue BP Thevissen K 《Cellular and molecular life sciences : CMLS》2008,65(13):2069-2079
Defensins are small (~5 kDa), basic, cysteine-rich antimicrobial peptides that fulfill an important role in the innate immunity of their host by combating pathogenic invading micro-organisms. Defensins can inhibit the growth or virulence of microorganisms directly or can do so indirectly by enhancing the host's immune system. Because of their wide distribution in nature, defensins are believed to be ancient molecules with a common ancestor that arose more than a billion years ago. This review summarizes current knowledge concerning the mode of antifungal action of plant, insect and human defensins. 相似文献
5.
Myosin I is a non-filamentous, single-headed, actin-binding motor protein and is present in a wide range of species from yeast to man. The role of these class I myosins have been studied extensively in simple eukaryotes, showing their role in diverse processes such as actin cytoskeleton organization, cell motility, and endocytosis. Recently, studies in metazoans have begun to reveal more specialized functions of myosin I. It will be a major challenge in the future to examine the physiological functions of each class I myosin in different cell types of metazoans. 相似文献
6.
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
7.
The identification of the aspartic protease BACE1 (β-secretase) was a defining event in research aimed at understanding the
molecular mechanisms that underlie Alzheimer’s disease (AD) pathogenesis. This is because BACE1 catalyses the rate limiting
step in the production of amyloid-β (Aβ) the principal component of plaque pathology in AD, the excessive production of which
is believed to be a primary cause of neurodegeneration, and cognitive dysfunction in AD. Subsequent discoveries showed that
genetic deletion of BACE1 completely abolishes Aβ production and deposition in vivo, and that BACE1 activity is significantly increased in AD brain. In this review we present current knowledge on BACE1, discussing
its structure, function and complex regulation with a view to understanding BACE1 function in the brain, and BACE1 as a target
in blocking aberrant Aβ production in AD.
Received 15 May 2008; received after revision 13 June 2008; accepted 18 June 2008 相似文献
8.
Structural biology of the purine biosynthetic pathway 总被引:1,自引:0,他引:1
Purine biosynthesis requires ten enzymatic transformations to generate inosine monophosphate. PurF, PurD, PurL, PurM, PurC,
and PurB are common to all pathways, while PurN or PurT, PurK/PurE-I or PurE-II, PurH or PurP, and PurJ or PurO catalyze the
same steps in different organisms. X-ray crystal structures are available for all 15 purine biosynthetic enzymes, including
7 ATP-dependent enzymes, 2 amidotransferases and 2 tetrahydrofolate-dependent enzymes. Here we summarize the structures of
the purine biosynthetic enzymes, discuss similarities and differences, and present arguments for pathway evolution. Four of
the ATP-dependent enzymes belong to the ATP-grasp superfamily and 2 to the PurM superfamily. The amidotransferases are unrelated,
with one utilizing an N-terminal nucleophileglutaminase and the other utilizing a triad glutaminase. Likewise the tetrahydrofolate-dependent
enzymes are unrelated. Ancestral proteins may have included a broad specificity enzyme instead of PurD, PurT, PurK, PurC,
and PurP, and a separate enzyme instead of PurM and PurL.
Received 26 May 2008; received after revision 30 June 2008; accepted 9 July 2008 相似文献
9.
The Agouti-Related Protein (AgRP) is a powerful orexigenic peptide that increases food intake when ubiquitously overexpressed or when administered centrally. AgRP-deficiency, on the other hand, leads to increased metabolic rate and a longer lifespan when mice consume a high fat diet. In humans, AgRP polymorphisms have been consistently associated with resistance to fatness in Blacks and Whites and resistance to the development of type-2 diabetes in African Blacks. Systemically administered AgRP accumulates in the liver, the adrenal gland and fat tissue while recent findings suggest that AgRP may also have inverse agonist effects, both centrally and peripherally. AgRP could thus modulate energy balance via different actions. Its absence or reduced functionality may offer a benefit both in terms of bringing about negative energy balance in obesigenic environments, as well as leading to an increased lifespan. 相似文献
10.
11.
Conti B 《Cellular and molecular life sciences : CMLS》2008,65(11):1626-1630
A modest reduction in body temperature prolongs longevity and may retard aging in both poikilotherm and homeotherm animals. Some of the possible mechanisms mediating these effects are considered here with respect to major aging models and theories. 相似文献
12.
Galat A 《Cellular and molecular life sciences : CMLS》2008,65(21):3481-3493
Extracellular domains of some cellular receptors expressed in the organisms at different levels of development belong to three-fingered
protein (TFP) fold. The Homo sapiens genome encodes at least 45 genes containing from one to three TFP domains (TFPDs), namely diverse paralogues of the Ly6 gene,
CD59 and the receptors of activins, bone morphogenetic proteins, Mullerian inhibiting substance and transforming growth factor-β.
C4.4a and urokinase/plasminogen activatory receptor contain two and three TFPD repeats, respectively. These diverse proteins
have a low overall sequence similarity with each other and their hydrophobicity levels vary to a considerable degree. It is
suggested that sequence differentiation within the TFPD led to distinct groups of proteins whose attributes were optimized
to fit both the physicochemical properties specific to their functional microenvironment and selective targeting of their
highly diversified extracellular cofactors.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 7 August 2008; accepted 29 August 2008 相似文献
13.
Cellular mechanisms regulating human melanogenesis 总被引:2,自引:0,他引:2
H. Y. Park M. Kosmadaki M. Yaar B. A. Gilchrest 《Cellular and molecular life sciences : CMLS》2009,66(9):1493-1506
14.
Bile acids and bile alcohols in the form of their conjugates are amphipathic end products of cholesterol metabolism with multiple physiological functions. The great variety of bile acids and bile alcohols that are present in vertebrates are tabulated. Bile salts have an enterohepatic circulation resulting from efficient vectorial transport of bile salts through the hepatocyte and the ileal enterocyte; such transport leads to the accumulation of a pool of bile salts that cycles between the liver and intestine. Bile salt anions promote lipid absorption, enhance tryptic cleavage of dietary proteins, and have antimicrobial effects. Bile salts are signaling molecules, activating nuclear receptors in the hepatocyte and ileal enterocyte, as well as an increasing number of G-protein coupled receptors. Bile acids are used therapeutically to correct deficiency states, to decrease the cholesterol saturation of bile, or to decrease the cytotoxicity of retained bile acids in cholestatic liver disease. 相似文献
15.
Katona RL Sinkó I Holló G Szucs KS Praznovszky T Kereso J Csonka E Fodor K Cserpán I Szakál B Blazsó P Udvardy A Hadlaczky G 《Cellular and molecular life sciences : CMLS》2008,65(23):3830-3838
Mammalian artificial chromosomes (MACs) are safe, stable, non-integrating genetic vectors with almost unlimited therapeutic
transgene-carrying capacity. The combination of MAC and stem cell technologies offers a new strategy for stem cell-based therapy,
the efficacy of which was confirmed and validated by using a mouse model of a devastating monogenic disease, galactocerebrosidase
deficiency (Krabbe’s disease). Therapeutic MACs were generated by sequence-specific loading of galactocerebrosidase transgenes
into a platform MAC, and stable, pluripotent mouse embryonic stem cell lines were established with these chromosomes. The
transgenic stem cells were thoroughly characterized and used to produce chimeric mice on the mutant genetic background. The
lifespan of these chimeras was increased twofold, verifying the feasibility of the development of MAC-stem cell systems for
the delivery of therapeutic genes in stem cells to treat genetic diseases and cancers, and to produce cell types for cell
replacement therapies.
Received 29 July 2008; received after revision 22 September 2008; accepted 24 September 2008 相似文献
16.
Improper protein folding (misfolding) can lead to the formation of disordered (amorphous) or ordered (amyloid fibril) aggregates.
The major lens protein, α-crystallin, is a member of the small heat-shock protein (sHsp) family of intracellular molecular
chaperone proteins that prevent protein aggregation. Whilst the chaperone activity of sHsps against amorphously aggregating
proteins has been well studied, its action against fibril-forming proteins has received less attention despite the presence
of sHsps in deposits found in fibril-associated diseases (e.g. Alzheimer’s and Parkinson’s). In this review, the literature
on the interaction of αB-crystallin and other sHsps with fibril-forming proteins is summarized. In particular, the ability
of sHsps to prevent fibril formation, their mechanisms of action and the possible in vivo consequences of such associations are discussed. Finally, the fibril-forming propensity of the crystallin proteins and its
implications for cataract formation are described along with the potential use of fibrillar crystallin proteins as bionanomaterials.
Received 13 June 2008; received after revision 29 July 2008; accepted 05 August 2008 相似文献
17.
Lin CI Chen CN Huang MT Lee SJ Lin CH Chang CC Lee H 《Cellular and molecular life sciences : CMLS》2008,65(17):2740-2751
Lysophosphatidic acid (LPA) is a low-molecular-weight lipid growth factor, which binds to G-protein-coupled receptors. Previous studies have shown that LPA enhances vascular endothelial growth factor-A (VEGF-A) expression in cancer cells and promotes angiogenesis process. However, the roles of LPA in lymphatic vessel formation and lymphangiogenesis have not been investigated. Here, we demonstrated that LPA up-regulated VEGF-C mRNA and protein expressions in human umbilical vein endothelial cells (HUVECs). Furthermore, the expression levels of lymphatic markers, including Prox-1, LYVE-1 and podoplanin, were enhanced in LPA-stimulated tube forming endothelial cells in vitro and in vivo. Moreover, we showed that pretreatment with MAZ51, a VEGFR-3 kinase inhibitor, and introduction of VEGFR-3 siRNA suppressed LPA-induced HUVEC tube formation and lymphatic marker expressions. These results demonstrated that LPA enhances expression of lymphatic markers through activating VEGF-C receptors in endothelial cells. This study provides basic information that LPA might be a target for therapeutics against lymphangiogenesis and tumor metastasis. 相似文献
18.
19.
Delgado M Pérez-Miguelsanz J Garrido F Rodríguez-Tarduchy G Pérez-Sala D Pajares MA 《Cellular and molecular life sciences : CMLS》2008,65(13):2080-2090
Wilson's disease is characterized by longterm hepatic accumulation of copper leading to liver disease with reduction of S-adenosylmethionine synthesis. However, the initial changes in this pathway remain unknown and constitute the objective of the present study. Using the Long Evans Cinnamon rat model, early alterations were detected in the mRNA and protein levels, as well as in the activities of several enzymes of the methionine cycle. Notably, the main change was a redox-mediated 80% decrease in the mRNA levels of the methionine adenosyltransferase regulatory subunit as compared to the control group. Moreover, changes in S-adenosylmethionine, S-adenosylhomocysteine, methionine and glutathione levels were also observed. In addition, in vitro experiments show that copper affects the activity and folding of methionine adenosyltransferase catalytic subunits. Taken together, these observations indicate that early copper accumulation alters methionine metabolism with a pattern distinct from that described previously for other liver diseases. 相似文献
20.
The multifunctional roles of the four-and-a-half-LIM only protein FHL2 总被引:14,自引:1,他引:14
Johannessen M Møller S Hansen T Moens U Van Ghelue M 《Cellular and molecular life sciences : CMLS》2006,63(3):268-284