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101.
Aldose reductase and aldehyde reductase belong to the aldo-keto reductase superfamily of enzymes whose members are responsible
for a wide variety of biological functions. Aldose reductase has been identified as the first enzyme involved in the polyol
pathway of glucose metabolism which converts glucose into sorbitol. Glucose over-utilization through the polyol pathway has
been linked to tissue-based pathologies associated with diabetes complications, which make the development of a potent aldose
reductase inhibitor an obvious and attractive strategy to prevent or delay the onset and progression of the complications.
Structural studies of aldose reductase and the homologous aldehyde reductase in complex with inhibitor were carried out to
explain the difference in the potency of enzyme inhibition. The aim of this review is to provide a comprehensive summary of
previous studies to aid the development of aldose reductase inhibitors that may have less toxicity problems than the currently
available ones.
Received 4 December 2006; received after revision 12 February 2007; accepted 20 April 2007 相似文献
102.
103.
Dreschers S Dumitru CA Adams C Gulbins E 《Cellular and molecular life sciences : CMLS》2007,64(2):181-191
Rhinoviruses, which cause common cold, belong to the Picornaviridae family, small non-enveloped viruses (diameter 15-30 nm) containing a single-stranded RNA genome (about 7 kb). Over 100 different rhinoviral serotypes have been identified thus far, establishing rhinoviruses as the most diverse group of Picornaviridae. Based on receptor binding properties, rhinoviruses are divided into two classes: the major group binding to intracellular adhesion molecule-1 and the minor group binding to the very low density lipoprotein receptors. Interactions between virus and the receptor molecules cause a conformational change in the capsid, which is a prerequisite for viral uptake. Rhinoviruses trigger a chemokine response upon infection that may lead to exacerbation of the symptoms of common cold, i.e. asthma and inflammation. The following review aims to summarize the knowledge about rhinoviral infections and discusses therapeutical approaches against this almost perfectly adapted pathogen. 相似文献
104.
The venoms of predatory cone snails harbor a rich repertoire of peptide toxins that are valuable research tools, but recently
have also proven to be useful drugs. Among the conotoxins with several disulfide bridges, the O-superfamily toxins are characterized
by a conserved cysteine knot pattern: C-C-CC-C-C. While ω-conotoxins and κ-conotoxins block Ca2+ and K+ channels, respectively, the closely related δ- and μO-conotoxins affect voltage-gated Na+ channels (Nav channels). δ-conotoxins mainly remove the fast inactivation of Nav channels and, thus, functionally resemble long-chain scorpion α-toxins. μO-conotoxins are functionally similar to μ-conotoxins,
since they inhibit the ion flow through Nav channels. Recent results from functional and structural assays have gained insight into the underlying molecular mechanisms.
Both types of toxins are voltage-sensor toxins interfering with the voltage-sensor elements of Nav channels.
Received 27 December 2006; received after revision 30 January 2007; accepted 19 February 2007 相似文献
105.
Receptor communication within the lymphocyte plasma membrane: a role for the thrombospondin family of matricellular proteins 总被引:1,自引:0,他引:1
Lymphocytes, the principal cells of the immune system, carry out immune surveillance throughout the body by their unique capacity
to constantly reposition themselves between a free-floating vascular state and a tissue state characterized by migration and
frequent adhesive interactions with endothelial cells and components of the extracellular matrix. Therefore, mechanisms co-ordinating
adhesion and migration with signals delivered through antigen recognition probably play a pivotal role for the regulation
of lymphocyte behaviour and function. Endogenous thrombospondin-1 (TSP-1) seems to be the hub in such a mechanism for autocrine
regulation of T cell adhesion and migration. TSP-1 functions as a mediator of cis interaction of vital receptors within the T lymphocyte plasma membrane, including integrins, low density lipoprotein receptor-related
protein, calreticulin and integrin-associated protein.
Received 1 June 2006; received after revision 28 June 2006; accepted 11 October 2006 相似文献
106.
Wang E Lenferink A O'Connor-McCourt M 《Cellular and molecular life sciences : CMLS》2007,64(14):1752-1762
Genomic alterations lead to cancer complexity and form a major hurdle for comprehensive understanding of the molecular mechanisms underlying oncogenesis. In this review, we describe recent advances in studying cancer-associated genes from a systems biology point of view. The integration of known cancer genes onto protein and signaling networks reveals the characteristics of cancer genes within networks. This approach shows that cancer genes often function as network hub proteins which are involved in many cellular processes and form focal nodes in information exchange between many signaling pathways. Literature mining allows constructing gene-gene networks, in which new cancer genes can be identified. The gene expression profiles of cancer cells are used for reconstructing gene regulatory networks. By doing so, genes which are involved in the regulation of cancer progression can be picked up from these networks, after which their functions can be further confirmed in the laboratory. 相似文献
107.
tRNase Z: the end is not in sight 总被引:1,自引:0,他引:1
Although the enzyme tRNase Z has only recently been isolated, a plethora of data has already been acquired concerning the
enzyme. tRNase Z is the endonuclease that catalyzes the removal of the tRNA 3′ trailer, yielding the mature tRNA 3′ end ready
for CCA addition and aminoacylation. Another substrate cleaved by tRNase Z is the small chromogenic phosphodiester bis(p-nitrophenyl)phosphate (bpNPP), which is the smallest tRNase Z substrate known so far. Hitherto the biological function as
tRNA 3′-end processing enzyme has been shown only in one prokaryotic and one eukaryotic organism, respectively. This review
summarizes the present information concerning the two tRNase Z substrates pre-tRNA and bpNPP, as well as the metal requirements
of tRNase Z enzymes.
Received 29 March 2007; received after revision 15 May 2007; accepted 21 May 2007 相似文献
108.
Lindahl E Nyman U Melles E Sigmundsson K Ståhlberg M Wahren J Obrink B Shafqat J Joseph B Jörnvall H 《Cellular and molecular life sciences : CMLS》2007,64(4):479-486
Proinsulin C-peptide is known to bind specifically to cell membranes and to exert intracellular effects, but whether it is
internalized in target cells is unknown. In this study, using confocal microscopy and immunostained or rhodamine-labeled peptide,
we show that C-peptide is internalized and localized to the cytosol of Swiss 3T3 and HEK-293 cells. In addition, transport
into nuclei was found using the labeled peptide. The internalization was followed at 37°C for up to 1 h, and was reduced at
4°C and after preincubation with pertussis toxin. Hence, it is concluded to occur via an energy-dependent, pertussis toxin-sensitive
mechanism and without detectable degradation within the experimental time course. Surface plasmon resonance measurements demonstrated
binding of HEK-293 cell extract components to C-peptide, and subsequent elution of bound material revealed the components
to be intracellular proteins. The identification of C-peptide cellular internalization, intracellular binding proteins, absence
of rapid subsequent C-peptide degradation and apparent nuclear internalization support a maintained activity similar to that
of an intracrine peptide hormone. Hence, the data suggest the possibility of one further C-peptide site of action.
Received 31 October 2006; received after revision 27 December 2006; accepted 30 December 2006 相似文献
109.
Kitamura T Kometani K Hashida H Matsunaga A Miyoshi H Hosogi H Aoki M Oshima M Hattori M Takabayashi A Minato N Taketo MM 《Nature genetics》2007,39(4):467-475
Inactivation of TGF-beta family signaling is implicated in colorectal tumor progression. Using cis-Apc(+/Delta716) Smad4(+/-) mutant mice (referred to as cis-Apc/Smad4), a model of invasive colorectal cancer in which TGF-beta family signaling is blocked, we show here that a new type of immature myeloid cell (iMC) is recruited from the bone marrow to the tumor invasion front. These CD34(+) iMCs express the matrix metalloproteinases MMP9 and MMP2 and the CC-chemokine receptor 1 (CCR1) and migrate toward the CCR1 ligand CCL9. In adenocarcinomas, expression of CCL9 is increased in the tumor epithelium. By deleting Ccr1 in the background of the cis-Apc/Smad4 mutant, we further show that lack of CCR1 prevents accumulation of CD34(+) iMCs at the invasion front and suppresses tumor invasion. These results indicate that loss of transforming growth factor-beta family signaling in tumor epithelium causes accumulation of iMCs that promote tumor invasion. 相似文献
110.