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1.
Ouellette AJ 《Cellular and molecular life sciences : CMLS》2011,68(13):2215-2229
Paneth cells at the base of small intestinal crypts of Lieberkühn secrete high levels of α-defensins in response to cholinergic
and microbial stimuli. Paneth cell α-defensins are broad spectrum microbicides that function in the extracellular environment
of the intestinal lumen, and they are responsible for the majority of secreted bactericidal peptide activity. Paneth cell
α-defensins confer immunity to oral infection by Salmonella enterica serovar Typhimurium, and they are major determinants of the composition of the small intestinal microbiome. In addition to
host defense molecules such as α-defensins, lysozyme, and Pla2g2a, Paneth cells also produce and release proinflammatory mediators
as components of secretory granules. Disruption of Paneth cell homeostasis, with subsequent induction of endoplasmic reticulum
stress, autophagy, or apoptosis, contributes to inflammation in diverse genetic and experimental mouse models. 相似文献
2.
Microtubules are fibrous elements in the cytoplasm of eukaryotic cells, where they perform a wide variety of functions. Microtubules
are major organizers of the cell interior and are vitally involved in motility events such as chromosome migration during
cell division. To fulfill their physiological function, microtubule arrays have to undergo dramatic changes in their spatial
arrangement, and this depends to a large extent on the complex and special dynamic properties of the individual polymers.
In this review we first describe the intrinsic dynamic properties of microtubules assembled in vitro from purified tubulin
and examine the relationships between these properties and microtubule functions. Subsequent sections concern microtubule
dynamics in vivo, their similarity and differences with microtubule dynamics in vitro, and the nature of the cellular regulators
which act on microtubule assemblies in physiological conditions.
Received 2 May 2001; received after revision 10 July 2001; accepted 10 July 2001 相似文献
3.
The intracellular signaling pathways mediating the nuclear exclusion of the androgen receptor (AR) by melatonin were evaluated
in PC3 cells stably transfected with the AR. The melatonin-induced nuclear exclusion of the AR by melatonin (100 nM, 3 h)
was blocked by LY 83583 (an inhibitor of guanylyl cyclases). 8-Bromo-cGMP (a cell-permeable cGMP analog), mimicked the effect
of melatonin, as did ionomycin (a calcium ionophore) and PMA [an activator of protein kinase C (PKC)], and their effects were
blocked by GF-109203X (a selective PKC inhibitor). BAPTA (an intracellular calcium chelator) blocked the effects of melatonin
and 8-bromo-cGMP but not of PMA. Inhibition or activation of the protein kinase A pathway did not affect basal or melatonin-mediated
AR localization. We conclude that the melatonin-mediated rise in cGMP elicits AR nuclear exclusion via a pathway involving
increased intracellular calcium and PKC activation. These results define a novel signaling pathway that regulates AR localization
and androgen responses in target cells.
Received 31 July 2001; received after revision 18 September 2001; accepted 30 October 2001 相似文献
4.
D.B. Moody 《Cellular and molecular life sciences : CMLS》2001,58(10):1461-1474
T cells are well known to recognize peptide antigens presented by major histocompatibility (MHC) class I or class II molecules.
More recently, the CD1 family of antigen-presenting molecules has been shown to present both mammalian and microbial glycolipid
antigens for specific recognition by T cells. Human CD1c proteins mediate T cell recognition of polyisoprenyl glycolipids,
evolutionarily conserved phosphoglycolipids, which function in glycan synthesis pathways. This family of antigenic molecules
is particularly attractive for the study of the molecular features that control T cell recognition of self and foreign glycolipids
because natural polyisoprenols from mammals, fungi, protozoa, mycobacteria and eubacteria differ in structure. Moreover, these
naturally occurring structural differences can influence their recognition by CD1c-restricted T cells. This review of the
structural diversity and evolutionary relationships of polyisoprenoid glycolipids emphasizes those features of polyisoprenyl
glycolipid biosynthesis that are relevant to their functions as targets of CD1-mediated T cell responses.
Received 16 March 2001; received after revision 19 April 2001; accepted 23 April 2001 相似文献
5.
Penaeidins, a family of antimicrobial peptides from penaeid shrimp (Crustacea, Decapoda) 总被引:13,自引:0,他引:13
Destoumieux D Munoz M Bulet P Bachère E 《Cellular and molecular life sciences : CMLS》2000,57(8-9):1260-1271
The production of antimicrobial peptides represents a first-line host defense mechanism of innate immunity that is widespread
in nature. Only recently such effectors were isolated in crustacean species, whereas numerous antimicrobial peptides have
been characterized from other arthropods, both insects and chelicerates. This review presents findings on a family of antimicrobial
peptides, named penaeidins, isolated from the shrimp Penaeus vannamei. Their structure and antimicrobial properties as well as their immune function will be discussed through analyses of penaeidin
gene expression and peptide distribution upon microbial challenge.
Received 21 January 2000; received after revision 10 March 2000; accepted 10 March 2000 相似文献
6.
The mitochondrial PHB complex: roles in mitochondrial respiratory complex assembly, ageing and degenerative disease 总被引:16,自引:0,他引:16
Nijtmans LG Artal SM Grivell LA Coates PJ 《Cellular and molecular life sciences : CMLS》2002,59(1):143-155
Although originally identified as putative negative regulators of the cell cycle, recent studies have demonstrated that the
PHB proteins act as a chaperone in the assembly of subunits of mitochondrial respiratory chain complexes. The two PHB proteins,
Phb1p and Phb2p, are located in the mitochondrial inner membrane where they form a large complex that represents a novel type
of membrane-bound chaperone. On the basis of its native molecular weight, the PHB-complex should contain 12-14 copies of both
Phb1p and Phb2p. The PHB complex binds directly to newly synthesised mitochondrial translation products and stabilises them
against degradation by membrane-bound metalloproteases belonging to the family of mitochondrial triple-A proteins. Sequence
homology assigns Phb1p and Phb2p to a family of proteins which also contains stomatins, HflKC, flotillins and plant defence
proteins. However, to date only the bacterial HflKC proteins have been shown to possess a direct functional homology with
the PHB complex. Previously assigned actions of the PHB proteins, including roles in tumour suppression, cell cycle regulation,
immunoglobulin M receptor binding and apoptosis seem unlikely in view of any hard evidence in their support. Nevertheless,
because the proteins are probably indirectly involved in ageing and cancer, we assess their possible role in these processes.
Finally, we suggest that the original name for these proteins, the prohibitins, should be amended to reflect their roles as
proteins that hold badly formed subunits, thereby keeping the nomenclature already in use but altering its meaning to reflect
their true function more accurately.
Received 21 May 2001; received after revision 2 July 2001; accepted 24 July 2001 相似文献
7.
Kaushal S Ghosh S Sharma N Sanyal SN Majumdar S 《Cellular and molecular life sciences : CMLS》2001,58(14):2098-2107
A 36-kDa phospholipid transfer protein (PLT-PR), which preferentially transfers phosphatidyl choline (PC) compared to phosphatidyl inositol (PI), was purified 827-fold
from rabbit lung homogenate. Incorporation of cholesterol in unilamellar vesicles reduced the PC transfer activity of PLTPR. Dipalmitoyl phosphatidyl choline uptake by alveolar type II cells was increased in the presence of the protein, and further
enhanced in the presence of surfactant liposomes. However, a decrease in uptake was noted with cholesterol in host membranes.
Incorporation of PI into host membranes had a low stimulatory effect on the process. All these effects were more pronounced
in adult type II cells compared to premature, term and 3-day-old pups.
Received 12 September 2001; accepted 11 October 2001 相似文献
8.
L.A. Pile F.W.-H. Lee D.A. Wassarman 《Cellular and molecular life sciences : CMLS》2001,58(11):1715-1718
We examined the consequences of the deacetylase inhibitor trichostatin A (TSA) on the development of Drosophila melanogaster. When fed to flies, TSA caused lethality and delayed development at concentrations as low as 5 μM, had stronger effects on
males than females, and acted synergistically with mutations in the gene encoding the RPD3 deacetylase to cause notched wings,
but did not appear to affect a SINA signaling pathway that is normally repressed by the SIN3 corepressor. These findings suggest
that deacetylated histones play an important role in normal developmental progression and establish parameters for genetic
screens to dissect the role of deacetylases in this process.
Received 14 June 2001; received after revision 31 July 2001; accepted 21 August 2001 相似文献
9.
Tetraspanins 总被引:12,自引:0,他引:12
The first tetraspanins were discovered on surface of human leucocytes, but it was rapidly demonstrated that they had a wider
tissue expression. Twenty-six molecules display sufficient homology to belong to the same superfamily. Their function is not
precisely known, but data coming from biochemical studies or knockout mice suggest that they play a major role in membrane
biology. One of their outstanding properties is their ability to form a network of multimolecular complexes, the 'tetraspanin
web', in which integrins are included. The structure of these complexes is under investigation, but some of the rules that
govern their organization have already been unraveled. The challenge is to determine how the organization of the 'tetraspanin
web' modifies the function of its constitutive molecules and consequently influences cellular behaviour. The implications
may be considerable for the understanding of basic cellular processes such as migration and also of diseases related to loss
or mutation of a single tetraspanin.
Received 29 December 2000; received after revision 26 February 2001; accepted 19 March 2001 相似文献
10.
Elevated levels of butyrylcholinesterase activity occur under a number of hypertriglyceridemic conditions, including diabetes
and obesity. This study examines whether butyrylcholinesterase activity has a direct effect on triglyceride production, using
Caco-2 cells, a human intestinal adenocarcinoma cell line. Caco-2 cells were incubated with 500 μM oleate to stimulate triglyceride
production, and butyrylcholinesterase activity was measured in the cellular homogenate. Butyrylcholinesterase activity was
approximately 3 × 10-3 mmol/min per milligram protein. Although triglyceride production increased by almost five-fold after 18 h of stimulation
with oleate, butyrylcholinesterase activity was not increased. Furthermore, inhibition of butyrylcholinesterase activity using
1 mM tetraisopropylpyrophosphoramide did not significantly affect triglyceride production or secretion. Human insulin (100
μU/ml) increased the production of butyrylcholinesterase without increasing triglyceride production. This demonstrates that
stimulation of fatty acid production and butyrylcholinesterase activity occur by independent mechanisms and suggests that
their correlation in hyperlipidemic conditions is not due to a direct relationship in production in situ.
Received 23 April 2001; received after revision 25 May 2001; accepted 20 June 2001 相似文献
11.
Molina H 《Cellular and molecular life sciences : CMLS》2002,59(2):220-229
Complement has an important role in inflammation and in the normal function of the immune system. Activated complement fragments
have the capacity to bind and damage self-tissues. Cells from vertebrates express on their surface regulators of complement
activation that protect them from the deleterious effects of cell-bound complement fragments. Abnormalities in these regulators
of complement activation may participate in the pathogenesis of autoimmune diseases and inflammatory disorders. Murine Crry
is one of these regulators that inhibits the activation of the third component of complement and protects self-tissues from
complement-mediated damage. Experimental work on Crry has increased our understanding of the immunobiology of complement regulation
and the potential role of complement and complement inhibitors in the development and treatment of human diseases.
Received 13 June 2001; received after revision 12 July 2001; accepted 9 August 2001 相似文献
12.
Significance and molecular targets of protein kinase A during cAMP-mediated protection of cold stored liver grafts 总被引:6,自引:0,他引:6
The use of marginal donor livers is followed by a higher frequency of primary dys- or nonfunction after transplantation.
The present study was designed to test the hypothesis that stimulation of the cAMP second-messenger signal pathway might protect
the liver from ischemic injury, laying emphasis on the role of protein kinase A-mediated signal transduction.?Rat livers were
harvested after 45 min of cardiac arrest and preserved in HTK solution for 24 h. Hepatic integrity was assessed thereafter
using a blood-free reperfusion model.?Supplementation of the preservation solution with dibutyryl-cAMP (db-cAMP) promoted
phosphorylation of BAD at Ser 112 and concomitantly mitigated mitochondrial release of cytochrome c into the cytosol. Apoptotic
cell transformation was evident in reperfused livers by positive TUNEL-staining of sinusoidal lining cells and the detection
of cleaved poly(ADP-ribose) polymerase (PARP) in tissue homogenates by western analysis. Treatment with db-cAMP was effective
in minimizing both TUNEL staining and PARP cleavage and significantly reduced postischemic enzyme leakage of alanine aminotransferase
to one half, while hepatic bile production was enhanced by approximately 60% when compared to untreated livers. This functional
improvement was accompanied by a net amelioration of portal vascular conductivity. Inhibition of A kinase-anchoring protein
with HT31 completely reversed any of the observed effects obtained by db-cAMP.?We conclude that enhancement of cellular cAMP
signal maintains hepatic integrity during and after ischemic preservation which may be attributed to protein kinase A dependent
phosphorylation of BAD in line with subsequent inhibition of mitochondria-initiated apoptosis of sinusoidal lining cells.
Received 12 July 2001; received after revision 14 August 2001; accepted 14 August 2001 相似文献
13.
Pycnogenol enhances immune and haemopoietic functions in senescence-accelerated mice 总被引:1,自引:0,他引:1
F. J. Liu Y. X. Zhang B. H. S. Lau 《Cellular and molecular life sciences : CMLS》1998,54(10):1168-1172
Pycnogenol (procyanidin extracted from Pinus maritima) has been shown to be a potent free radical scavenger and an antioxidant phytochemical. The effects of pycnogenol on immune
and haemopoietic dysfunction in senescence-accelerated mice (SAM), as a murine model of accelerated ageing, were determined.
SAMP8, a strain of senile-prone mice, exhibit learning and memory deficits, immunodeficiency and dysfunction of the haemopoietic
system. Oral feeding with pycnogenol for 2 months significantly improved their T- and B-cell function. Pycnogenol also augmented
the proliferative capacity of haemopoietic progenitors of bone marrow in SAMP8. These data suggest that pycnogenol may be
useful for either retardation or restoration of parameters associated with ageing.
Received 3 July 1998; accepted 28 July 1998 相似文献
14.
The Ror receptor tyrosine kinase family 总被引:6,自引:0,他引:6
Forrester WC 《Cellular and molecular life sciences : CMLS》2002,59(1):83-96
Receptor tyrosine kinases (RTKs) participate in numerous developmental decisions. Ror RTKs are a family of orphan receptors
that are related to muscle specific kinase (MuSK) and Trk neurotrophin receptors. MuSK assembles acetylcholine receptors at
the neuromuscular junction [1, 2], and Trk receptors function in the developing nervous system (reviewed in [3-5]). Rors have
been identified in nematodes, insects and mammals. Recent studies have begun to shed light on Ror function during development.
In most species, Rors are expressed in many tissue types during development. Analyses of mutants that are defective in the
single nematode Ror demonstrate a role in cell migration and in orienting cell polarity. Mice lacking one of the two Ror gene
products display defects in bone and heart formation. Similarly, two different human bone development disorders, dominant
brachydactyly B and recessive Robinow syndrome, result from mutations in one of the human Ror genes.
Received 17 April 2001; received after revision 2 July 2001; accepted 4 July 2001 相似文献
15.
In the hepatitis delta virus, ribozymes are encoded in both the genomic strand RNA and its complement, the antigenomic strand.
The two ribozymes are similar in sequence and structure, are most active in the presence of divalent cation and catalyze RNA
cleavage reactions which generate a 5′-hydroxyl group and a 2′,3′-cyclic phosphate group. Recent progress has been made in
understanding the catalytic mechanism. One key was a crystal structure of the genomic ribozyme that revealed a specific cytosine
positioned to act as a general acid-base catalyst. The folding of the ribozyme in the context of the longer viral RNA is another
area of interest. The biology requires that each ribozyme act only once, and mechanisms proposed for regulation of ribozyme
activity sometimes invoke alternative RNA structures. Likewise, interference of ribozyme function by polyadenylation of the
antigenomic RNA strand could be controlled through alternative structures, and a model for such control is proposed.
Received 21 June 2001; received after revision 18 July 2001; accepted 20 July 2001 相似文献
16.
Extracellular electron transfer 总被引:23,自引:0,他引:23
Results from several laboratories indicate that extracellular electron transfer may be a general mechanism whereby microoorganisms
generate energy for cell growth and/or maintenance. Specifically, bacteria can use redox-active organic small molecules, generated
outside or inside the cells, to shuttle electrons between reduced and oxidized compounds. Electron shuttling has now been
reported for several different bacterial species, and exchanges of shuttling compounds may even syntrophically link diverse
organisms in nature. Biofilm systems in both geological and clinical settings are likely to be important environments for
metabolisms that employ extracellular electron transfer. Both structural and functional analyses suggest that electron shuttles
and some virulence factors may be related to one another.
Received 21 March 2001; received after revision 10 May 2001; accepted 11 May 2001 相似文献
17.
Aging appears to be an irreversible process. Here we report that nicotinamide (NAA) can induce rapid and reversible reversion
of aging phenotypes in human diploid fibroblasts in terms of cell morphology and senescence-associated β-galactosidase activity.
Although NAA seems to enhance the replicative potential of the cells, it has little effect on their growth rate and life span,
suggesting that NAA action is rather separated from the cellular replicative system. The effects are unique to NAA: none of
the NAA-related compounds examined (an NAD precursor/niacin, NAD analogs, and poly(ADP-ribose) polymerase inhibitors) exerted
similar effects. Thus, NAD-related metabolism and poly(ADP-ribosyl)ation are unlikely related to the NAA action. On the other
hand, histone acetyltransferase (HAT) activity was elevated in NAA-exposed cells, while in aged cells, HAT activity and histone
H4 acetylation were lowered. Taken together, the results suggest that NAA may cause rejuvenation by restoring, at least in
part, altered gene expression in aged cells through its activation of HAT.
Received 27 August 2001; received after revision 15 October 2001; accepted 15 October 2001 相似文献
18.
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
19.
In the early 1990s, the search for protein kinases led to the discovery of a novel family of non-receptor tyrosine kinases,
the Janus kinases or JAKs. These proteins were unusual because they contained two kinase homology domains and no other known
signaling modules. It soon became clear that these were not ‘just another’ type of kinase. Their ability to complement mutant
cells insensitive to interferons and to be activated by a variety of cytokines demonstrated their central signaling function.
Now, as we approach the end of the decade, it is evident from biochemical studies to knockout mice that JAKs play non-redundant
functions in development, differentiation, and host defense mechanisms. Here, recent progress is reviewed, with particular
emphasis on structure-function studies aimed at revealing how this family of tyrosine kinases is regulated. 相似文献
20.
Meilang Xue Nikita Minhas Shu-Oi Chow Suat Dervish Philip N. Sambrook Lyn March Christopher J. Jackson 《Cellular and molecular life sciences : CMLS》2010,67(9):1537-1546
Circulating protein C (PC) plays a vital role as an anti-coagulant and anti-inflammatory mediator. We show here that human endothelial cells produce PC that acts through novel mediators to enhance their own functional integrity. When endogenous PC or its receptor, endothelial protein C receptor (EPCR), was suppressed by small interfering (si) RNA, human umbilical cord endothelial cell (HUVEC) proliferation was decreased and apoptosis elevated. Interestingly, PC or EPCR siRNA significantly increased HUVEC permeability, which is likely via reduction of the angiopoietin (Ang)1/Ang2 ratio and inhibition of the peripheral localization of the tight junction protein, zona occludins-1. In addition, PC or EPCR siRNA inhibited type IV collagen and matrix metalloproteinase-2, providing the first evidence that PC contributes to vascular basement membrane formation. These newly described actions of endogenous PC act to stabilize endothelial cells and enhance barrier function, to potentially promote the functional integrity of blood vessels. 相似文献