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1.
Apoptotic cell death in the lactating mammary gland is enhanced by a folding variant of α-lactalbumin 总被引:1,自引:0,他引:1
Apoptosis is essential to eliminate secretory epithelial cells during the involution of the mammary gland. The environmental regulation of this process is however, poorly understood. This study tested the effect of HAMLET (human -lactalbumin made lethal to tumor cells) on mammary cells. Plastic pellets containing HAMLET were implanted into the fourth inguinal mammary gland of lactating mice for 3 days. Exposure of mammary tissue to HAMLET resulted in morphological changes typical for apoptosis and in a stimulation of caspase-3 activity in alveolar epithelial cells near the HAMLET pellets but not more distant to the pellet or in contralateral glands. The effect was specific for HAMLET and no effects were observed when mammary glands were exposed to native a-lactalbumin or fatty acid alone. HAMLET also induced cell death in vitro in a mouse mammary epithelial cell line. The results suggest that HAMLET can mediate apoptotic cell death in mammary gland tissue.Received 30 January 2004; received after revision 5 March 2004; accepted 16 March 2004 相似文献
2.
Nakano A 《Cellular and molecular life sciences : CMLS》2004,61(2):186-191
The yeast Saccharomyces cerevisiae is one of the best-studied organisms to understand molecular mechanisms of membrane traffic, but as far as the organization of the Golgi apparatus is concerned, yeast is only just beginning to yield clues about how dynamic and flexible the organelle is. 相似文献
3.
Protein folding and degradation in bacteria: to degrade or not to degrade? That is the question 总被引:11,自引:0,他引:11
In Escherichia coli protein quality control is carried out by a protein network, comprising chaperones and proteases. Central to this network
are two protein families, the AAA+ and the Hsp70 family. The major Hsp70 chaperone, DnaK, efficiently prevents protein aggregation
and supports the refolding of damaged proteins. In a special case, DnaK, together with the assistance of the AAA+ protein
ClpB, can also refold aggregated proteins. Other Hsp70 systems have more specialized functions in the cell, for instance HscA
appears to be involved in the assembly of Fe/S proteins. In contrast to ClpB, many AAA+ proteins associate with a peptidase
to form proteolytic machines which remove irreversibly damaged proteins from the cellular pool. The AAA+ component of these
proteolytic machines drives protein degradation. They are required not only for recognition of the substrate but also for
substrate unfolding and translocation into the proteolytic chamber. In many cases, specific adaptor proteins modify the substrate
binding properties of AAA+ proteins. While chaperones and proteases do not appear to directly cooperate with each other, both
systems appear to be necessary for proper functioning of the cell and can, at least in part, substitute for one another.
RID="*"
ID="*"Corresponding author. 相似文献
4.
The p53 protein was discovered 20 years ago, as a cellular protein tightly bound to the large T oncoprotein of the SV40 DNA
tumour virus. Since then, research on p53 has developed in many exciting and sometimes unexpected directions. p53 is now known
to be the product of a major tumour suppressor gene that is the most common target for genetic alterations in human cancer.
The nonmutated wild-type p53 protein (wtp53) is often found within cells in a latent state and is activated in response to
various intracellular and extracellular signals. Activation involves an increase in overall p53 protein levels, as well as
qualitative changes in the protein. Upon activation, wtp53 can induce a variety of cellular responses, most notable among
which are cell cycle arrest and apoptosis. To a great extent, these effects are mediated by the ability of p53 to activate
specific target genes. In addition, the p53 protein itself possesses biochemical functions which may facilitate DNA repair
as well as apoptosis. The role of p53 in normal development and particularly in carcinogenesis has been elucidated in depth
through the use of mouse model systems. The insights provided by p53 research over the years are now beginning to be utilized
towards better diagnosis, prognosis and treatment of cancer. 相似文献
5.
Nestin expression – a property of multi-lineage progenitor cells? 总被引:13,自引:0,他引:13
Wiese C Rolletschek A Kania G Blyszczuk P Tarasov KV Tarasova Y Wersto RP Boheler KR Wobus AM 《Cellular and molecular life sciences : CMLS》2004,61(19-20):2510-2522
Tissue-specific progenitor cells are characterized by proliferation and differentiation, but, in contrast to embryonic stem (ES) cells, have limited capacities for self-renewal and no tumourigenic potential. These latter traits make progenitor cells an ideal source for regenerative cell therapies. In this review, we describe what is currently known about nestin, an intermediate filament first identified in neuroepithelial stem cells. During embryogenesis, nestin is expressed in migrating and proliferating cells, whereas in adult tissues, nestin is mainly restricted to areas of regeneration. We show that nestin is abundant in ES-derived progenitor cells that have the potential to develop into neuroectodermal, endodermal and mesodermal lineages. Although it remains unclear what factors regulate in vitro and in vivo expression of nestin, we conclude that nestin represents a characteristic marker of multi-lineage progenitor cells and suggest that its presence in cells may indicate multi-potentiality and regenerative potential. 相似文献
6.
Lamarine M Mornon JP Berezovsky N Chomilier J 《Cellular and molecular life sciences : CMLS》2001,58(3):492-498
Using a set of 372 proteins representative of a variety of 56 distinct globular folds, a statistical correlation was observed
between two recently revealed features of protein structures: tightened end fragments or 'closed loops', i. e. sequence fragments
that are able in three-dimensional (3D) space to nearly close their ends (a current parameter of polymer physics), and 'topohydrophobic
positions', i. e. positions always occupied in 3D space by strong hydrophobic amino acids for all members of a fold family.
Indeed, in sequence space, the distribution of preferred lengths for tightened end fragments and that for topohydrophobic
separation match. In addition to this statistically significant similarity, the extremities of these 'closed loops' may be
preferentially occupied by topohydrophobic positions, as observed on a random sample of various folds. This observation may
be of special interest for sequence comparison of distantly related proteins. It is also important for the ab initio prediction
of protein folds, considering the remarkable topological properties of topohydrophobic positions and their paramount importance
within folding nuclei. Consequently, topohydrophobic positions locking the 'closed loops' belong to the deep cores of protein
domains and might have a key role in the folding process.
Received 1 February 2001; accepted 7 February 2001 相似文献
7.
8.
Unraveling the pathogenesis of Parkinson’s disease – the contribution of
monogenic forms 总被引:2,自引:0,他引:2
The field of Parkinsons disease pathogenesis is rapidly evolving from the one of a monolithic and obscure entity into the one of a complex scenario with several known molecular players. The ongoing systematic exploration of the genome holds great promise for the identification of the genetic factors conferring susceptibility to the common non-Mendelian forms of this disease. However, most of the progress of the last 5 years has come from the successful mapping and cloning of genes responsible for rare Mendelian variants of Parkinsons disease. These discoveries are providing tremendous help in understanding the molecular mechanisms of this devastating disease. Here we review the genetics of the monogenic forms of Parkinsons disease. Moreover, we focus on the mechanisms of disease caused by -synuclein and parkin mutations, and the implications of this growing body of knowledge for understanding the pathogenesis of the common forms of the disease.
Received 10 March 2004; received after revision 26 April 2004; accepted 29 April 2004 相似文献
9.
Antonenkov VD Rokka A Sormunen RT Benz R Hiltunen JK 《Cellular and molecular life sciences : CMLS》2005,62(23):2886-2895
Mouse liver peroxisomes were isolated by centrifugation in a self-generated Percoll gradient followed by an Optiprep density
gradient centrifugation. Peroxisomes contributed 90–96% of the total protein content in the fraction, as confirmed by marker
enzyme assays, protein pattern in SDS-PAGE, immunoblotting, and electron microscopy. Solubilized peroxisomal membrane proteins
were reconstituted into a planar lipid bilayer. A single-channel conductance monitoring of the reconstituted lipid bilayer
revealed the presence of two pore-forming components with a conductance in 1 M KCl of 1.3 nS and 2.5 nS. Control experiments
with fractions enriched in mitochondria, lysosomes, and fragments of endoplasmic reticulum showed that the peroxisomal channel-forming
activities were not due to admixture of isolated peroxisomes with other cellular organelles. The peroxisomal channels were
well preserved in membrane preparations but became unstable after solubilization from the membranes by detergent.
Received 27 May 2005; received after revision 23 September 2005; accepted 11 October 2005 相似文献
10.
F. E. Weber J. H. Dyer F. López García M. Werder T. Szyperski K. Wüthrich H. Hauser 《Cellular and molecular life sciences : CMLS》1998,54(7):751-759
The preform of the rabbit sterol carrier protein 2 (pre-rSCP2) was cloned, the uniformly 15N-labelled protein expressed in Escherichia coli and studied by three-dimensional 15N-resolved nuclear magnetic resonance spectroscopy. In spite of its low solubility in aqueous solution of only ∼0.3 mM, sequential
15N and 1H backbone resonance assignments were obtained for 105 out of the 143 residues. From comparison of the sequential and medium-range
nuclear Overhauser effects (NOEs) in the two proteins, all regular secondary structures previously determined in mature human
SCP2 (hSCP2) [Szyperski et al. (1993) FEBS Lett. 335: 18–26] were also identified in pre-rSCP2. Near-identity of the backbone 15N and 1H chemical shifts and 1 : 1 correspondence of 24 long-range NOEs to backbone amide groups in the two proteins show that the
residues 21 – 143 adopt the same globular fold in pre-rSCP2 and mature hSCP2. The N-terminal 20-residue leader peptide of pre-rSCP2 is flexibly disordered in solution and does not observably affect the conformation of the polypeptide segment 21 – 143.
Received 11 May 1998; accepted 15 May 1998 相似文献
11.
Anti herpes simplex virus activity of lactoferrin/lactoferricin – an example of antiviral activity of antimicrobial protein/peptide 总被引:3,自引:0,他引:3
Jenssen H 《Cellular and molecular life sciences : CMLS》2005,62(24):3002-3013
One of the most common viral infections in humans is caused by the herpes simplex virus (HSV). It was first effectively treated
in the 1970s with the introduction of acyclovir, which is still the most commonly used treatment. Naturally occurring antimicrobial
proteins and peptides have also been shown to possess antiviral activity against HSV. This review will focus on the anti-HSV
activity of one such protein, lactoferrin, and a small peptide fragment from its N-terminal domain, lactoferricin. Both components
have been shown to effectively block entry of HSV into the host cell. In addition to blocking HSV entry, the peptides appear
to have immune stimulatory activity, although this is still somewhat controversial. Mode of action studies and knowledge about
the anti-HSV activity of lactoferricin have also been successfully employed in the design of new, more specific HSV blockers.
Received 25 May 2005; received after revision 24 August 2005; accepted 6 September 2005 相似文献