Disease relevance of HSPA4

• Heat stress has no effect on the composition of the p56.hsp.70.hsp90 complex, except that the complex derived from heat shocked-cells contains both the constitutive and heat-inducible forms of hsp70 [1].
• We investigated antibodies to recombinant human hsp60, recombinant Mycobacterium bovis hsp65 and to stress-inducible recombinant human hsp70 using enzyme-linked immunosorbent assay (ELISA) in sera of 209 juvenile idiopathic arthritis (JIA) patients and 50 healthy controls [2].
• We conclude that an increased T cell response to mycobacterial hsp70 may be present in patients with multiple sclerosis [3].
• Humoral immune response to the chlamydial heat shock proteins hsp60 and hsp70 in Chlamydia-associated chronic salpingitis with tubal occlusion [4].
• In this symposium, we review the association of hsps with humoral immunity to candidosis and aspergillosis, cellular immunity to histoplasmosis, and the identification of hsp70 in another dimorphic fungus, Paracoccidioides brasiliensis [5].

Psychiatry related information on HSPA4

• These results suggest that the age-dependent decrease in hsp 70 in olfactory receptor neurons of older subjects and those with Alzheimer's disease may be attributable to their greater susceptibility to stress [6].

High impact information on HSPA4

• However, expression of the p53 gene and heat shock gene hsp 70 was not affected in these clones, indicating the existence of a specific regulatory linkage between c-fos and c-myc genes [7].
• Cytoplasmic chaperones in precursor targeting to mitochondria: the role of MSF and hsp 70 [8].
• A similar correlation for hsp60 and mycobacterial hsp70 did not achieve significance [9].
• Still unclear, however, is exactly why most eukaryotic cells, in contrast to prokaryotic cells, express a novel form of hsp 70 (i.e., hsp 72) after experiencing stress [10].
• In cells exposed to either an amino acid analog or sodium arsenite, two potent inducers of the stress response, newly synthesized proteins bind to but are not released from hsp 70 [11].

Chemical compound and disease context of HSPA4

• METHOD: Expression of hsp60, hsp70, and hsp90 in placentae from 12 women with preterm birth, eight with intrauterine growth restriction (IUGR), and 10 with term birth, as well as the presence of the corresponding antibodies, was investigated by a new carbocyanine double fluorescence technique [12].
• The effects of okadaic acid (OA), a potent and specific inhibitor of serine/threonine phosphatases 2A and 1, on the transient expression of a human hsp 70 promoter-linked chloramphenicol acetyltransferase gene transfected into N-18 mouse neuroblastoma cells were determined [13].

Biological context of HSPA4

• In situ hybridization localized the single copy hsp70 RY gene to the long arm of chromosome 5 at 5 q31.1-5 q31.2 [14].
• Using apg-1 cDNA as a probe, we isolated a novel cDNA, apg-2 from a mouse testis cDNA library, which was highly homologous to human hsp70RY [15].
• In the hsp70 reaction cycle, short segments of polypeptide bind rapidly and weakly to the ATP state, so triggering hydrolysis and consequent stabilization of the complex [16].
• Invariant leu preceding turn motif phosphorylation site controls the interaction of protein kinase C with hsp70 [17].
• Allosteric regulation of hsp70 chaperones involves a conserved interdomain linker [18].

Anatomical context of HSPA4

• Molecular cloning of a novel human hsp70 from a B cell line and its assignment to chromosome 5 [14].
• While induction of hsp70 transcripts was observed in mouse TAMA26 Sertoli cells and NIH/3T3 fibroblasts on temperature shift from 37 degrees C to 42 degrees C (traditional heat shock) or from 32 degrees C to 39 degrees C, apg-2 transcripts were not induced under either condition [15].
• Immunohistochemistry showed that hsp65 and hsp70 homologues were expressed in the synovial membrane in these patients but not in controls [9].
• In addition to interacting with glucocorticoid receptors, the p56 protein of IM-9 cell cytosol is also found as part of a large heteromeric complex that contains both the 70-kDa and 90-kDa heat shock proteins (hsp70 and hsp90, respectively) [1].
• We show that stimulation of murine and human macrophages with the heat shock proteins gp96 and hsp70 results in induction of inducible NO synthase and the production of NO [19].

Associations of HSPA4 with chemical compounds

• Copper sulfate inducibility of a pHhsp70 construct expressing the enhanced green fluorescent protein (EGFP) gene under the control of the exogenous human hsp70 promoter was tested in transfected CHSE 214 cells and transgenic zebrafish (Danio rerio) [20].
• Addition of monomethyl L-arginine monoacetate, competitive inhibitor of NOS, inhibited nitric oxide (NO) production and apoptosis of gammadeltaT lymphocytes induced by hsp60 and hsp70 [21].
• HCMV infection of HFF cells resulted in increased abundance of ornithine decarboxylase, thymidine kinase, heat-shock protein 70 (hsp70), and brain creatine kinase transcripts [22].
• These results suggest that the regulatory mechanism and/or the signals for hsp60 induction by cadmium are independent from those of hsp70 and metallothionein [23].
• Hsp70 expression was inhibited by treatment with quercetin or overexpressed by transfection of plasmids harboring the hsp70 gene [24].

Physical interactions of HSPA4

• We examined the induction, by heat shock, of heat shock transcription factor (HSTF) DNA-binding and hsp 70 gene promoter activities during aging of the IMR-90 human diploid fibroblasts [25].

Regulatory relationships of HSPA4

• Co-operative binding of hsp60 may promote transfer from hsp70 and correct folding of imported proteins in mitochondria [corrected] [26].

Other interactions of HSPA4

• In addition, immunosuppressive and/or antiinflammatory activity of CsA can be executed via CyP-40 and hsp 70 complexed with SR, and following the interaction with CyP-related receptor of NK and with IL-8 [27].
• In contrast, in the RVV group, 11 (45.8%) were hsp60-positive and eight (33.3%) were hsp70-positive [28].
• By use of specific antibodies, we identified the fourth receptor subunit as a 59-kDa protein (p59); we did not obtain any evidence for the heat shock protein hsp70 being a receptor component [29].
• Myeloma cells were transfected with the hsp70 gene under beta-actin gene promoter [30].
• Analysis of whole cytosolic extracts by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography reveal an increased rate of radiolabeling for hsp70, hsp90, hsp100, ad hsp110, but no heat-inducible protein of smaller relative molecular mass is detected [1].

Analytical, diagnostic and therapeutic context of HSPA4

• It was shown by electrophoresis and immunoblotting that a common sign of the cells which in vitro underwent such different harmful influences as ATP depletion, heat shock, oxidative stress, and SH reagent treatment was significant insolubilization of actin and 70-kDa heat-shock protein (hsp70) [31].
• Patients with acute GVHD had a significant increase in IgM anti-hsp70 and/or anti-hsp90 early (30-90 days) after transplantation [32].
• Surface expression of hsp60 and hsp70 on oesophageal tumours and Daudi cells was demonstrated by flow cytometry [33].
• In the present study, the synthesis of parasite heat shock proteins (hsp60, hsp70, and hsp90) was shown to be enhanced at a temperature of 39 C and the results of immunoprecipitation analysis indicated that parasite HSPs are highly immunogenic in T. cruzi-infected mice maintained at 36 C or room temperature (RT) [34].
• The gene encoding a 70-kDa heat shock protein, hsp70, was not up-regulated (i.e., more highly expressed) as a part of the diapause program, nor was it up-regulated by desiccation stress, but it was up-regulated during recovery from cold shock [35].

References