共查询到20条相似文献,搜索用时 125 毫秒
1.
Favatier F Jacquier-Sarlin MR Swierczewski E Polla BS 《Cellular and molecular life sciences : CMLS》1999,56(7-8):701-708
A bi-allelic polymorphism found in the regulatory region of the human heat shock (HS) protein (HSP) hsp70-1 gene, which comprises an A-->C transversion, 3 bp upstream of the HS element (HSE), has been associated with extended HLA haplotypes. In view of the chaperoning and protective functions of Hsp70, we investigated whether this hsp70-1 bi-allelic polymorphism could modulate the stress response, which may relate to enhanced resistance or susceptibility to certain diseases. We compared the basal and HS-induced HS factor (HSF)-binding activity of the two polymorphic HSEs, hsp70-1 mRNA accumulation and HSP expression in two human Epstein Barr virus (EBV)-transformed B cell lines typed for hsp70-1 promoter alleles. Our results suggest that hsp70-1 promoter polymorphism does not influence HSF-binding activity, hsp70 mRNA accumulation or synthesis in human EBV-transformed B cell lines. 相似文献
2.
Jadwiga Jabłońska Magda Dubińska-Magiera Teresa Jagla Krzysztof Jagla Małgorzata Daczewska 《Cellular and molecular life sciences : CMLS》2018,75(23):4341-4356
The Drosophila Hsp67Bc gene encodes a protein belonging to the small heat-shock protein (sHSP) family, identified as the nearest functional ortholog of human HSPB8. The most prominent activity of sHSPs is preventing the irreversible aggregation of various non-native polypeptides. Moreover, they are involved in processes such as development, aging, maintenance of the cytoskeletal architecture and autophagy. In larval muscles Hsp67Bc localizes to the Z- and A-bands, which suggests its role as part of the conserved chaperone complex required for Z-disk maintenance. In addition, Hsp67Bc is present at neuromuscular junctions (NMJs), which implies its involvement in the maintenance of NMJ structure. Here, we report the effects of muscle-target overexpression of Drosophila Hsp67Bc hot-spot variants Hsp67BcR126E and Hsp67BcR126N mimicking pathogenic variants of human HSPB8. Depending on the substitutions, we observed a different impact on muscle structure and performance. Expression of Hsp67BcR126E affects larval motility, which may be caused by impairment of mitochondrial respiratory function and/or by NMJ abnormalities manifested by a decrease in the number of synaptic boutons. In contrast, Hsp67BcR126N appears to be an aggregate-prone variant, as reflected in excessive accumulation of mutant proteins and the formation of large aggregates with a lesser impact on muscle structure and performance compared to the Hsp67BcR126E variant. 相似文献
3.
Chiara Giommarelli Valentina Zuco Enrica Favini Claudio Pisano Fabrizio Dal Piaz Nunziatina De Tommasi Franco Zunino 《Cellular and molecular life sciences : CMLS》2010,67(6):995-1004
Curcumin, a natural polyphenol, has been described to exhibit effects on signaling pathways, leading to induction of apoptosis.
In this study, we observed that curcumin inhibited Hsp90 activity causing depletion of client proteins implicated in survival
pathways. Based on this observation, this study was designed to investigate the cellular effects of curcumin combination with
the pan-HDAC inhibitors, vorinostat and panobinostat, which induce hyperacetylation of Hsp90, resulting in inhibition of its
chaperone function. The results showed that, at subtoxic concentrations, curcumin markedly sensitized tumor cells to vorinostat-
and panobinostat-induced growth inhibition and apoptosis. The sensitization was associated with persistent depletion of Hsp90
client proteins (EGFR, Raf-1, Akt, and survivin). In conclusion, our findings document a novel mechanism of action of curcumin
and support the therapeutic potential of curcumin/HDAC inhibitors combination, because the synergistic interaction was observed
at pharmacologically achievable concentrations, which were ineffective when each drug was used alone. 相似文献
4.
Y. Aron M. Vayssier-Taussat M. Bachelet B.S. Polla 《Cellular and molecular life sciences : CMLS》2001,58(10):1522-1527
The anti-ulcer drug geranylgeranylacetone (GGA) has been shown to induce the expression of heat shock proteins (HSPs), in particular of Hsp70, in gastric and small intestine cells. In this study, we investigated whether GGA was able to induce Hsp70 in another cell type, human monocytes, which represent a well-established model of Hsp70 expression under oxidative stress. In these cells, GGA had no significant effect either on basal or tobacco smoke-induced Hsp70 expression. We further investigated the effects of GGA on mitochondria, a key organelle of oxidant-mediated cell injury and a putative target for GGA-mediated protection. GGA significantly increased basal mitochondrial membrane polarization and inhibited the decrease in mitochondrial membrane potential of human monocytes exposed to distinct sources of clinically relevant oxidants such as tobacco smoke and y-irradiation. Our results indicate that mitochondria are targets for GGA-mediated protection against oxidative stress in human monocytes, independently of Hsp70. 相似文献
5.
R. A. Stuart D. M. Cyr W. Neupert 《Cellular and molecular life sciences : CMLS》1994,50(11-12):1002-1011
The family of hsp70 (70 kilodalton heat shock protein) molecular chaperones plays an essential and diverse role in cellular physiology, Hsp70 proteins appear to elicit their effects by interacting with polypeptides that present domains which exhibit non-native conformations at distinct stages during their life in the cell. In this paper we review work pertaining to the functions of hsp70 proteins in chaperoning mitochondrial protein biogenesis. Hsp70 proteins function in protein synthesis, protein translocation across mitochondrial membranes, protein folding and finally the delivery of misfolded proteins to proteolytic enzymes in the mitochondrial matrix. 相似文献
6.
Differential basal synthesis of Hsp70/Hsc70 contributes to interindividual variation in Hsp70/Hsc70 inducibility 总被引:7,自引:0,他引:7
Boshoff T Lombard F Eiselen R Bornman JJ Bachelet M Polla BS Bornman L 《Cellular and molecular life sciences : CMLS》2000,57(8-9):1317-1325
The source of intraspecies variation in the expression of heat shock proteins (HSPs) remains unresolved but could shed light
on differential stress tolerance and disease susceptibility. This study investigated the influence of variable basal HSP synthesis
on differential inducibility of HSP synthesis. Basal and heat-induced synthesis of the major HSP families in peripheral blood
monocytes from healthy donors (n=42) were analysed using biometabolic labelling and densitometry. Basal Hsp70/Hsc70 synthesis
and percentage induction of Hsp70/Hsc70 synthesis were significantly correlated (r=−0.57, p<0.0001), and described most accurately
by an exponential decay equation (R=0.68, R2=0.46). This regression equation suggests that increasing levels of basal Hsp70/Hsc70 synthesis are accompanied byan exponential
decrease in the percentage induction of Hsp70/Hsc70 synthesis. The model fits data from European and non-European population
groups independently, although both coefficients in the regression equation were larger for non-Europeans. This implies population
group as an additional factor influencing differential HSP expression. The differential inducibility of Hsp70/Hsc70 due to
variable basal synthesis of Hsp70/Hsc70 and based upon population group may contribute to differential stress tolerance or
disease susceptibility.
Received 27 March 2000; received after revision 19 June 2000; accepted 20 June 2000 相似文献
7.
8.
Hsp70 chaperones: Cellular functions and molecular mechanism 总被引:36,自引:0,他引:36
Hsp70 proteins are central components of the cellular network of molecular chaperones and folding catalysts. They assist a large variety of protein folding processes in the cell by transient association of their substrate binding domain with short hydrophobic peptide segments within their substrate proteins. The substrate binding and release cycle is driven by the switching of Hsp70 between the low-affinity ATP bound state and the high-affinity ADP bound state. Thus, ATP binding and hydrolysis are essential in vitro and in vivo for the chaperone activity of Hsp70 proteins. This ATPase cycle is controlled by co-chaperones of the family of J-domain proteins, which target Hsp70s to their substrates, and by nucleotide exchange factors, which determine the lifetime of the Hsp70-substrate complex. Additional co-chaperones fine-tune this chaperone cycle. For specific tasks the Hsp70 cycle is coupled to the action of other chaperones, such as Hsp90 and Hsp100.Received 21 October 2004; received after revision 24 November 2004; accepted 6 December 2004 相似文献
9.
Goh YC Yap CT Huang BH Cronshaw AD Leung BP Lai PB Hart SP Dransfield I Ross JA 《Cellular and molecular life sciences : CMLS》2011,68(9):1581-1592
Heat-shock protein 60 (Hsp60) is a highly conserved stress protein which has chaperone functions in prokaryotes and mammalian
cells. Hsp60 is associated with the mitochondria and the plasma membrane through phosphorylation by protein kinase A, and
is incorporated into lipid membranes as a protein-folding chaperone. Its diverse intracellular chaperone functions include
the secretion of proteins where it maintains the conformation of precursors and facilitates their translocation through the
plasma membrane. We report here that Hsp60 is concentrated in apoptotic membrane blebs and translocates to the surface of
cells undergoing apoptosis. Hsp60 is also enriched in platelets derived from terminally differentiated megakaryocytes and
expressed at the surface of senescent platelets. Furthermore, the exposure of monocytic U937 cells to Hsp60 enhanced their
phagocytic activity. Our results suggests that externalized Hsp60 in apoptotic cells and senescent platelets influences events
subsequent to apoptosis, such as the clearance of apoptotic cells by phagocytes. 相似文献
10.
Small heat shock proteins: molecular structure and chaperone function 总被引:17,自引:0,他引:17
Small heat shock proteins (sHSPs) associate with nuclei, cytoskeleton and membranes, and as molecular chaperones they bind
partially denatured proteins, thereby preventing irreversible protein aggregation during stress. sHSP monomers consist of
a conserved α-crystallin domain of approximately 90 amino acid residues, bordered by variable amino- and carboxy-terminal
extensions. The sHSPs undergo dynamic assembly into mono- and poly-disperse oligomers where the rate of disassembly affects
chaperoning. The α-crystallin domain contains several β-strands organized into two β-sheets responsible for dimer formation,
the basic building block of most sHSPS. The amino-terminal extension modulates oligomerization, subunit dynamics and substrate
binding, whereas the flexible carboxy-terminal extension promotes solubility, chaperoning and oligomerization, the latter
by inter-subunit linkage. Crystallization studies have revealed sHSP structure and function. Additionally, site-directed mutagenesis,
biophysical investigations, functional studies and the discovery of relationships between mutated sHSPs and diseases have
illuminated the role of sHSP within cells.
Received 8 May 2005; received after revision 24 June 2005; accepted 19 July 2005 相似文献
11.
Heat-shock protein 90, a chaperone for folding and regulation 总被引:21,自引:0,他引:21
Picard D 《Cellular and molecular life sciences : CMLS》2002,59(10):1640-1648
Heat-shock protein 90 (Hsp90) is an abundant and highly conserved molecular chaperone that is essential for viability in
eukaryotes. Hsp90 fulfills a housekeeping function in contributing to the folding, maintenance of structural integrity and
proper regulation of a subset of cytosolic proteins. A remarkable proportion of its substrates are proteins involved in cell
cycle control and signal transduction. Hsp90 acts with a cohort of Hsp90 co-chaperones that modulate its substrate recognition,
ATPase cycle and chaperone function. The large conformational flexibility of Hsp90 and a multitude of dynamic co-chaperone
complexes contribute to generating functional diversity, and allow Hsp90 to assist a wide range of substrates. 相似文献
12.
Giovanni Di Maira Francesca Brustolon Lorenzo A. Pinna Maria Ruzzene 《Cellular and molecular life sciences : CMLS》2009,66(20):3363-3373
Akt (PKB) is a critical kinase in cell-survival pathways. Its activity depends on the phosphorylation of Thr308 and Ser473,
by PDK1 and mTORC2, respectively. We found that Akt can be further stimulated through phosphorylation of Ser129 by another
kinase, CK2. Here we show that phosphorylation of Akt at Ser129 also facilitates its association with Hsp90 chaperone, thus
preventing Thr308 dephosphorylation. This is supported by the following observations: (1) phospho-Thr308 decreases when Ser129
is mutated to alanine, (2) this decrease is abolished by cell treatment with okadaic acid (to inactivate PP2A) or geldanamycin
(to inactivate Hsp90), (3) phosphorylation of Ser129 neither enhances the activity of PDK1 nor hampers the in vitro activity
of PP2A on Thr308, but increases the Hsp90 association to Akt. These data support the view that the antiapoptotic potential
of CK2 is at least in part mediated by its ability to maintain Akt in its active form. 相似文献
13.
Doerwald L van Genesen ST Onnekink C Marín-Vinader L de Lange F de Jong WW Lubsen NH 《Cellular and molecular life sciences : CMLS》2006,63(6):735-743
The mechanism of the translational thermotolerance provided by the small heat shock proteins (sHsps) αB-crystallin or Hsp27
is unknown. We show here that Hsp27, but not αB-crystallin, increased the pool of mobile stress granule-associated enhanced
green fluorescent protein (EGFP)-eukaryotic translation initiation factor (eIF)4E in heat-shocked cells, as determined by
fluorescence recovery after photobleaching. Hsp27 also partially prevented the sharp decrease in the pool of mobile cytoplasmic
EGFP-eIF4G. sHsps did not prevent the phosphorylation of eIF2α by a heat shock, but promoted dephosphorylation during recovery.
Expression of the C-terminal fragment of GADD34, which causes constitutive dephosphorylation of eIF2α, fully compensated for
the stimulatory effect of αB-crystallin on protein synthesis in heat-shocked cells, but only partially for that of Hsp27.
Our data show that sHsps do not prevent the inhibition of protein synthesis upon heat shock, but restore translation more
rapidly by promoting the dephosphorylation of eIF2α and, in the case of Hsp27, the availability of eIF4E and eIF4G.
Received 9 December 2005; received after revision 16 January 2006; accepted 23 January 2006 相似文献
14.
Dario C. Altieri 《Cellular and molecular life sciences : CMLS》2013,70(14):2463-2472
Although essential for energy production and cell fate decisions, the mechanisms that govern protein homeostasis, or proteostasis, in mitochondria are only recently beginning to emerge. Fresh experimental evidence has uncovered a role of molecular chaperones of the heat shock protein 90 (Hsp90) family in overseeing the protein folding environment in mitochondria. Initially implicated in protection against cell death, there is now evidence that Hsp90-directed protein quality control in mitochondria connects to hosts of cellular homeostatic networks that become prominently exploited in human cancer. 相似文献
15.
Heat shock protein 60: regulatory role on innate immune cells 总被引:1,自引:0,他引:1
Human heat shock protein 60 (Hsp60) exhibits immunoregulatory properties, primarily by inducing pro-inflammatory responses
in innate immune cells. Extensive analyses identified specific receptor structures for the interaction of Hsp60 with these
cells. The existence of distinct receptor structures responsible for Hsp60 binding and for Hsp60-induced release of pro-inflammatory
mediators has been demonstrated, implying that the interaction of Hsp60 with innate immune cells is a multifaceted process.
Distinct Hsp60 epitopes responsible for binding to innate immune cells and for the activation of these cells have been identified.
Depending on the cell-type, the amino acid (aa) region 481–500 or the regions aa241–260, aa391–410 and aa461–480 are involved
in Hsp60-binding to innate immune cells. An entirely different Hsp60-region, aa354–365 was found to bind lipopolysaccharide,
thereby mediating the pro-inflammatory effects of Hsp60. Because of its immunoregulatory properties, Hsp60 has been proposed
to act as intercellular danger signal, controlling innate and adaptive immune reactions.
Received 19 September 2006; received after revision 13 October 2006; accepted 13 December 2006 相似文献
16.
A central dogma in biology is the conversion of genetic information into active proteins. The biosynthesis of proteins by
ribosomes and the subsequent folding of newly made proteins represent the last crucial steps in this process. To guarantee
the correct folding of newly made proteins, a complex chaperone network is required in all cells. In concert with ongoing
protein biosynthesis, ribosome-associated factors can interact directly with emerging nascent polypeptides to protect them
from degradation or aggregation, to promote folding into their native structure, or to otherwise contribute to their folding
program. Eukaryotic cells possess two major ribosome-associated systems, an Hsp70/Hsp40-based chaperone system and the functionally
enigmatic NAC complex, whereas prokaryotes employ the Trigger Factor chaperone. Recent structural insights into Trigger Factor
reveal an intricate cradle-like structure that, together with the exit site of the ribosome, forms a protected environment
for the folding of newly synthesized proteins.
Received 29 June 2005; received after revision 4 August 2005; accepted 18 August 2005 相似文献
17.
Vigilanza P Aquilano K Rotilio G Ciriolo MR 《Cellular and molecular life sciences : CMLS》2008,65(6):991-1004
We have studied the effects of superoxide production after Cu,Zn superoxide dismutase (SOD1) down-regulation by RNA interference.
We demonstrated that SOD1 depletion induced, only in neuroblastoma cells, a decrease in actin and β-tubulin content and accumulation
of neurofilament light chain and Tau proteins. Alterations of cell morphology and the microfilament network were also observed,
together with the up-regulation of the Cdk5/p35 pathway, which is involved in the regulation of actin polymerization. The
decrease of filamentous actin was transient and was recovered through the activation of p38/Hsp27 MAPK pathway, as well as
after treatment with N-acetyl-L-cysteine. The importance of p38 in the recovery of cytoskeleton was confirmed by experiments carried out in the
presence of its inhibitor SB203580, which induced cell death. Our data demonstrate that SOD1 is essential for the preservation
of cytoskeleton integrity, by maintaining physiological concentration of reactive oxygen species and inhibiting the activation
of the neuronal specific Cdk5/p35 pathway.
P. Vigilanza, K. Aquilano: Both authors equally contributed to this work.
Received 15 November 2007; received after revision 19 January 2008; accepted 22 January 2008 相似文献
18.
Kabakov AE Budagova KR Malyutina YV Latchman DS Csermely P 《Cellular and molecular life sciences : CMLS》2004,61(24):3076-3086
BRX-235 (Iroxanadine), a novel drug developed by Biorex (Hungary), was previously characterized as a vasculoprotector against atherosclerosis, an activator of p38 kinase, and an enhancer of stress-responsive heat shock protein (Hsp) expression. The present data demonstrate that BRX-235 may improve survival of vascular endothelial cells (ECs) following ischemia/reperfusion stress. ECs cultured from human umbilical veins were exposed to hypoxia/reoxygenation to mimic ischemia/reperfusion. Caspase activation and apoptosis were monitored in the reoxygenated cells. Addition of BRX-235 (0.1–1 M) to culture medium prior to hypoxia or at start of reoxygenation significantly reduced the caspase-dependent apoptosis. The cytoprotection conferred by the pre-hypoxic drug administration was sensitive to quercetin and seems to be based on enhanced Hsp accumulation in stressed ECs. In the case of post-hypoxic drug administration, the cytoprotection was strongly inhibited by SB202190 and SB203580 and appears to be associated with enhanced p38 kinase activation in reoxygenated ECs.Received 12 May 2004; received after revision 7 September 2004; accepted 24 September 2004 相似文献
19.
Anurag Kumar Singh Michael P. Manns Ursula Seidler 《Cellular and molecular life sciences : CMLS》2011,68(6):1041-1051
Drug resistance continues to be a stumbling block in achieving better cure rates in several cancers. Doxorubicin is commonly
used in treatment of a wide range of cancers. The aim of this study was to look into the mechanisms of how low ambient pH
may contribute to down-regulation of apoptotic pathways in a gastric tumour cell line. Low pH culture conditions were found
to dramatically prolong cell survival after doxorubicin treatment, an effect that was in part reversed by co-incubation with
the specific p38 mitoge-activated protein kinase (MAP kinase) inhibitor SB203580, only mildly inhibited by blockade of the
multi-drug resistance 1 (MDR1) transporter, but completely abolished by siRNA-mediated knockdown of the heat shock protein
27 (HSP27). In conclusion, acidic pH causes less accumulation of cytotoxic drug in the nucleus of adeno gastric carcinoma
(AGS) cells and HSP27-dependent decrease in FasR-mediated gastric epithelial tumour cell apoptosis. 相似文献
20.
Molecular mechanisms of desiccation tolerance in the resurrection glacial relic Haberlea rhodopensis
Tsanko S. Gechev Maria Benina Toshihiro Obata Takayuki Tohge Neerakkal Sujeeth Ivan Minkov Jacques Hille Mohamed-Ramzi Temanni Andrew S. Marriott Ed Bergström Jane Thomas-Oates Carla Antonio Bernd Mueller-Roeber Jos H. M. Schippers Alisdair R. Fernie Valentina Toneva 《Cellular and molecular life sciences : CMLS》2013,70(4):689-709