Disease relevance of Hspa1a

• Striatal Hsp70 mRNA increased about 2-fold over control levels at 16 hr after AMPH-induced hyperthermia, and was the only Hsp species to significantly increase in response to AMPH [1].
• The exposure of the animals to in vivo heat stress was shown to induce the synthesis of otherwise non-existing Hsp72, rendering Hsc70 level unchanged in comparison to unstressed controls [2].
• Exercise, antioxidants, and HSP72: protection against myocardial ischemia/reperfusion [3].
• Characterization of spinal HSP72 induction and development of ischemic tolerance after spinal ischemia in rats [4].
• HSP72 appears to play a crucial protective role in modulating the gene expression controlled by NF-kappaB in sepsis [5].

Psychiatry related information on Hspa1a

• These results indicate that previous physical activity potentiates HSP72 expression after a wide range of stressors [6].
• Available evidence suggests that the stress response is an important component of cellular defense mechanisms, and that successful accumulation of hsp72 is critical to survival following ischemia [7].
• (2) Since HSP72 is induced for 1 to 2 weeks, the prolonged psychological side effects of MK-801, ketamine, phencyclidine, and related drugs could be related to this injury [8].
• A chronic unpredictable stress model used to produce depressive disorders in adult rats was applied to neonatal rats to investigate whether this type of stress can induce changes in the expression of Hsp70 and oestrogen receptor alpha in the oviduct, as detected by immunohistochemistry [9].

High impact information on Hspa1a

• Expression of Hsp 110, inducible Hsp 70, and Hsp 25 was greater in the hyperosmotic papilla than the isosmotic cortex but was not affected by the animal's hydration state [10].
• These data demonstrate that glucocorticoids protect intestinal epithelial cells against oxidant-induced stress by inducing hsp72 [11].
• Dexamethasone treatment also significantly induces hsp72 protein expression in rat intestinal mucosal cells in vivo [11].
• Antisense hsp72 cDNA transfection of IEC-18 cells abolishes the dexamethasone-induced hsp72 response, without significantly affecting constitutive expression of its homologue, hsc73 [11].
• Dexamethasone stimulates a time- and dose-dependent response in hsp72 protein expression that parallels its effects on cell viability [11].

Chemical compound and disease context of Hspa1a

• Thyroxine has two opposing effects: 1) direct repressive on rapid hsp72 transcription after heat stress; and 2) indirect stimulatory via beta-adrenergic signaling [12].
• Oral administration of geranylgeranylacetone (GGA), an antiulcer drug, enhanced HSP72 induction and reduced cerebral vasospasm [13].
• The exposure of the cells to a low concentration (0.1-3 microg/ml) of anisomycin for a few hours after heat stress stimulated the accumulation of the small stress proteins Hsp27 and alphaB-crystallin, but not that of Hsp70 [14].
• We report that gene transfer therapy with defective herpes simplex virus vectors overexpressing hsp72 improves neuron survival against focal cerebral ischemia and systemic kainic acid administration [15].
• Sodium arsenite (Ars) or hyperthermia (43 degrees C) induced the synthesis of hsp72 messenger RNA (mRNA) and protein in hepatocytes, indicating activation of the HSR [16].

Biological context of Hspa1a

• Restriction fragment length polymorphism of the major histocompatibility complex-linked heat shock protein 70 (Hsp70) genes of the rat [17].
• DNAs from inbred rat strains representing eighteen major histocompatibility complex (RT1) haplotypes have been tested for restriction fragment length polymorphisms of the three heat shock protein 70 (Hsp70) genes mapping into this complex [17].
• Because apoptosis induced in Y3 cells by heat shock is not affected, Hsp70 appears to interfere selectively with the CTL-induced lethal pathway that is found to be calcium but not caspase dependent [18].
• It is suggested that after heat shock Hsp70 enhances the CTL-induced apoptotic pathway by chaperoning certain proteins in the target cell that are involved in the execution of cell death [18].
• Evidence is now presented that Hsp70 is able to prevent the induction of the resistant phenotype [18].

Anatomical context of Hspa1a

• Two-fold increases in Hsp70 mRNA were also seen in primary cultures of rat cerebrum 24 hr after heat shock [1].
• We have reported previously that heat shock confers resistance to CTL in the rat myeloma cell line Y3 that is Hsp70 defective [18].
• Heat shock or transfection with heat shock protein 70 (Hsp70) genes has been shown to protect tumor cell lines against immune mechanisms of cytotoxicity [18].
• In Con A-stimulated lymphocytes and in lymphocyte x Y3 somatic cell hybrid clones a severe, non-Hsp70-inducing heat shock elicits resistance to CTL in contrast to a heat shock that results in Hsp70 expression [18].
• In the present study the association of glucocorticoid receptor with constitutive and inducible forms of Hsp70 in the liver cytosol of rats exposed to 41 degrees C whole body hyperthermic stress was examined [19].

Associations of Hspa1a with chemical compounds

• Low thyroxine could account for diminished HSP72 synthesis via lower heat production and thermoregulatory set point [12].
• CsA treatment in Con rats had no effects on muscle mass, fiber size, MHC composition, and Hsp72 or CaN levels [20].
• This study investigated if SLH induces in vivo HSP72 expression and whether in vitro HSP72 induction by sodium arsenite (NaArs) alters intracellular signal transduction and cytokine production similar to SLH [21].
• SLH mphi had more HSP72 protein before and after LPS compared with shams [21].
• Like SLH, mphi with induced HSP72 expression, have an attenuated TNF response [21].

Regulatory relationships of Hspa1a

• Therefore, PC that results in brain tolerance/neuroprotection increases neuronal Hsp70 in the PC cortex and activated astrocytic Hsp27 in the PC cortex in a temporal fashion associated with developing IT [22].
• The percentage of beta-galactosidase and Bcl-2 coexpressing neurons in HSP72-treated rats after global cerebral ischemia (84 +/- 4%) was greater than that in control vector-treated rats (58 +/- 9%) [23].
• CONCLUSION: These results demonstrated that ecto-5'-nucleotidase activated by an overexpression of HSP72 attenuated ischemia-reperfusion injury in the rat myocardium [24].
• An exception is the skeletal muscle, where HSP 72 is constitutively expressed in muscles that express the beta myosin heavy chain (beta-MHC) protein [25].
• Heat shock induced HSP72 expression in most inner ear tissues of the rat examined by immunoblotting [26].

Other interactions of Hspa1a

• In vitro HSP72 induction is associated with increased p38 phosphorylation [21].
• Protein-damaging stresses activate c-Jun N-terminal kinase via inhibition of its dephosphorylation: a novel pathway controlled by HSP72 [27].
• Glucocorticoid hormone receptor exists in the cytoplasm of target cells in the form of dynamic multiprotein heterocomplexes with heat shock proteins Hsp90 and Hsp70, and additional components of the molecular chaperone machinery [19].
• The 70-kDa heat shock proteins (Hsp70), including the cognates (Hsc70), are molecular chaperones that prevent misfolding and aggregation of polypeptides in cells under both normal and stressed conditions [28].
• As an example of single gene analysis, the RT1-linked heat shock-inducible heat shock genes Hsp70-1 and Hsp70-2 have been studied [29].

Analytical, diagnostic and therapeutic context of Hspa1a

• Analyses included Western blotting for myocardial HSP72 and HSF-1, electromobility shift assays for HSF-1 activation, and Northern blotting for HSP72 mRNA [30].
• HSP25 and HSP72 expression were assessed by immunoblot and immunohistochemistry [31].
• Immunoprecipitation of glucocorticoid receptor heterocomplexes by monoclonal anti-receptor antibody (BuGR2) followed by quantitative immunoblotting revealed the presence of both nucleocytoplasmic Hsp70 family members, constitutive--Hsc70 and inducible--Hsp72, within the complexes [19].
• Hyperthermia-induced HSP72 overexpression is attenuated with senescence [30].
• In the present study, using an aortic balloon occlusion model in rats, we characterized the effect of transient noninjurious (3 or 6 min) or injurious intervals (10 min) of spinal ischemia followed by 4-72 h of reflow on spinal expression of HSP72 and GFAP protein [4].

References