共查询到8条相似文献,搜索用时 4 毫秒
1.
Molecular pathology and pathobiology of osteoarthritic cartilage 总被引:14,自引:0,他引:14
The biochemical properties of articular cartilage rely on the biochemical composition and integrity of its extracellular
matrix. This matrix consists mainly of a collagen network and the proteoglycan-rich ground substance. In osteoarthritis, ongoing
cartilage matrix destruction takes place, leading to a progressive loss in joint function. Beside the degradation of molecular
matrix components, destabilization of supramolecular structures such as the collagen network and changes in the expression
profile of matrix molecules also take place. These processes, as well as the pattern of cellular reaction, explain the pathology
of osteoarthritic cartilage degeneration. The loss of histochemical proteoglycan staining reflects the damage at the molecular
level, whereas the supramolecular matrix destruction leads to fissuring and finally to the loss of the cartilage. Chondrocytes
react by increasing matrix synthesis, proliferating, and changing their cellular phenotype. Gene expression mapping in situ
and gene expression profiling allows characterization of the osteoarthritic cellular phenotype, a key determinant for understanding
and manipulating the osteoarthritic disease process. 相似文献
2.
Horvat A Nikezić G Petrović S Kanazir DT 《Cellular and molecular life sciences : CMLS》2001,58(4):636-644
The subsynaptosomal distribution and specific binding of 17beta-estradiol in vitro to mitochondria isolated from presynaptic nerve endings of female rat brain were examined. 17Beta-estradiol is (i) distributed unequally in synaptosomes and mitochondria posses the highest capacity to bind estradiol with respect to the available amount of the hormone. (ii) Estradiol binds specifically to isolated synaptosomal mitochondria. A Michaelis-Menten plot of specific binding was sigmoidal within a concentration range of 0.1-5 nM of added estradiol, with a saturation plateau at 3 nM. Binding of higher estradiol concentrations demonstrated an exponential Michaelis-Menten plot, indicating non-specific binding to mitochondria. Vmax and Km for the sigmoidal-shape range were estimated as 46 +/- 6 fmol of estradiol/mg of mitochondrial proteins and 0.46 +/- 0.07 nM free estradiol respectively. (iii) Estradiol binding is not affected by the removal of ovaries. The results show that inhibition of Na-dependent Ca2+ efflux from mitochondria by estradiol occurs according to an affinity change of the translocator for Na+, at the same estradiol concentrations that show specific binding to mitochondrial membranes. These data imply that physiological concentrations of estradiol, acting on mitochondrial membrane properties, extragenomically modulate the mitochondrial, and consequently the synaptosomal content of Ca2+, and in that way exert a significant change in nerve cell homeostasis. 相似文献
3.
H.-O. Ito T. Ueda Y. Hashimoto T. Imoto T. Koga 《Cellular and molecular life sciences : CMLS》1997,53(1):51-60
We previously generated a monoclonal antibody (mAb) against a putative pathogenic epitope on native type II collagen (CII)
for the induction of collagen-induced arthritis in mice (mAb1), and an anti-idiotypic mAb which appears to possess the internal
image of the CII epitope (mAb2). In the present study, the structural basis of the antigen/mAb1 and mAb1/mAb2 interactions
was examined. When partially SH-reduced mAb1 was analysed on Western blots, only fragments containing both heavy (H) and light
(L) chains were recognized by mAb2. When mAb2 was partially SH-reduced, only fragments containing both H and L chains were
recognized by mAb1. H and L chains were separated from mAb1 in a reduced, denatured condition, and each chain and a mixture
of the two were refolded. mAb2 reacted specifically to the renatured whole IgG molecule of mAb1, but not to the refolded L
or to H chains. Recombinant single chain Fv (scFv) generated from mAb1 and mAb2 had properties of the original mAbs, whereas
genetical
ly constructed chimeric scFvs, consisting of VH from mAb1 and an irrelevant VL , or VL of mAb1 and an irrelevant VH , did not react either to CII or to mAb2. Thus, interactions among CII, mAb1 and mAb2 appear to depend on quaternary structures
containing different protein subunits. These observations support the internal image property of the mAb2. In addition, this
dependency on quaternary structure for recognition of proteins may also be relevant to other protein-protein interactions.
Received 29 July 1996; received after revision 13 September 1996; accepted 18 October 1996 相似文献
4.
M. G. Taylor K. Simkiss J. Simmons L. N. Y. Wu R. E. Wuthier 《Cellular and molecular life sciences : CMLS》1998,54(2):196-202
A phosphatidyl serine-amorphous calcium phosphate complex has been synthesized as a model of the matrix vesicle system that is associated with the induction of mineral deposition in bone, cartilage and dentine. The complex has been studied using a novel technique of subtractive extended X-ray absorption fine structure (EXAFS). This enables spectra of the components of the molecules to be subtracted from the complex so as to identify the sites of interaction. The results suggest there is a movement in the nitrogen atom of the phosphatidyl serine which approaches the calcium atom in the mineral phase. This interpretation would link the membrane structure of the vesicle to the structure of the mineral in a way that could explain some of its roles in biomineralization. Received 14 November 1997; accepted 23 December 1997 相似文献
5.
The V(D)J recombination activating protein RAG2 consists of a six-bladed propeller and a PHD fingerlike domain, as revealed by sequence analysis 总被引:3,自引:0,他引:3
The RAG1 and RAG2 proteins play a crucial role in V(D)J recombination by cooperating to make specific double-stranded DNA breaks at a pair of recombination signal sequences (RSSs). However, the exact function they perform has heretofore remained elusive. Using a combination of sensitive methods of sequence analysis, we show here that the active core region of the RAG2 protein, confined to the first three quarters of its sequence, is in fact composed of a six-fold repeat of a 50-residue motif which is related to the kelch/mipp motif. This motif, which forms a four-stranded twisted antiparallel β sheet, is arranged in a circular formation like blades of a propeller or turbine. Given the known properties of the β-propeller fold in mediating protein-protein interactions, it is proposed that this six-laded propeller structure of the RAG2 active core would play a crucial role in the tight complex formed by the RAG1 and RAG2 proteins and RSSs. Moreover, the presence of a plant homeodomain finger-like motif in the last quarter of the RAG2 sequence suggests a potential interaction of this domain with chromatin components. Received 6 June 1998; accepted 9 June 1998 相似文献
6.
Grimm DR Colter MB Braunschweig M Alexander LJ Neame PJ Kim HK 《Cellular and molecular life sciences : CMLS》2001,58(1):148-159
Factor V is a plasma protein essential for blood coagulation. This protein is involved in activated protein C resistance,
the most common inherited thrombotic disorder known. We utilized the polymerase chain reaction to clone the porcine factor
V gene by generating overlapping clones amplified with primers chosen by comparison with known nucleotide sequences. The porcine
factor V cDNA contig encodes a predicted 2258-amino acid protein, making it the largest in comparison to the bovine, human,
and murine proteins. Porcine factor V has the highest level of homology with bovine factor V, but also has high levels of
conservation of important residues with all the species. Radiation hybrid mapping assigned the porcine factor V gene to chromosome
4. Three-dimensional models of factor V were generated and used to analyze membrane-binding sites in terms of conserved, and
therefore likely important residues.
Received 3 October 2000; revised 23 November 2000; accepted 6 December 2000 相似文献
7.
Symons MC 《Cellular and molecular life sciences : CMLS》2000,57(7):999-1007
This review emphasises the need to use spectroscopy in order to understand the behaviour of water, and summarises the background
of the subject. The various forms of spectroscopy that are especially informative are described, with particular reference
to near-infrared (NIR) spectrophotometry. The key results are outlined, first those obtained with small molecules and ions,
and second those involving proteins, DNA and cell membranes. Finally, some interpretations are offered which include the novel
but possibly controversial concept of free OH and free lone-pair groups. 相似文献
8.
V. A. Maltsev H. N. Sabbah M. Tanimura M. Lesch S. Goldstein A. I. Undrovinas 《Cellular and molecular life sciences : CMLS》1998,54(6):597-605
Abnormalities of contractile function have been identified in cardiomyocytes isolated from failed human hearts and from hearts
of animals with experimentally induced heart failure (HF). The mechanism(s) responsible for these functional abnormalities
are not fully understood. In the present study, we examined the relationship between action potential duration, pattern of
contraction and relaxation, and associated intracellular Ca2+ transients in single cardiomyocytes isolated from the left ventricle (LV) of dogs (n = 7) with HF produced by multiple sequential intracoronary microembolizations. Comparisons were made with LV cardiomyocytes
isolated from normal dogs. Action potentials were measured in isolated LV cardiomyocytes by perforated patch clamp, Ca2+ transients by fluo 3 probe fluorescence, and cardiomyocyte contraction and relaxation by edge movement detector. HF cardiomyocytes
exhibited an abnormal pattern of contraction and relaxation characterized by an attenuated initial twitch (spike) followed
by a sustained contracture ('dome') of 1 to 8 s in duration and subsequent delayed relaxation. This pattern was more prominent
at low stimulation rates (58% at 0.2 Hz, n = 211, 21% at 0.5 Hz, n = 185). Measurements of Ca2+ transients in HF cardiomyocytes at 0.2 Hz manifested a similar spike and dome configuration. The dome phase of both the contraction/relaxation
pattern and Ca2+ transients seen in HF cardiomyocytes coincided with a sustained plateau of the action potential. Shortening of the action
potential duration by administration of saxitoxin (100 nM) or lidocaine (30 μM) reduced the duration of the dome phase of
both the contraction/relaxation profile as well as that of the Ca2+ transient profile. An increase of stimulation rate up to 1 Hz caused shortening of the action potential and disappearance
of the spike-dome profile in the majority of HF cardiomyocytes. In HF cardiomyocytes, the action potential and Ca2+ transient duration were not significantly different from those measured in normal cells. However, the contraction-relaxation
cycle was significantly longer in HF cells (314 ± 67 ms, n = 21, vs. 221 ± 38 ms, n = 46, mean ± SD), indicating impaired excitation-contraction uncou pling in HF cardiomyocytes. The results show that, in
cardiomyocytes isolated from dogs with HF, contractile abnormalities and abnormalities of intracellular Ca2+ transients at low stimulation rates are characterized by a spike-dome configuration. This abnormal pattern appears to result
from prolongation of the action potential.
Received 22 January 1998; received after revision 16 March 1998; accepted 27 March 1998 相似文献