Disease relevance of HSPA1A

• Escherichia coli expressed cardiac Hsp70 stimulated a 2-fold increase in calcineurin (CaN) activity [1].
• Deletion of one of the duplicated Hsp70 genes causes hereditary myopathy of diaphragmatic muscles in Holstein-Friesian cattle [2].
• This increase in HSP 70 mRNA after repetitive brief ischemia was transient, occurring as early as 1 h and returning to baseline by 24 h after ischemia [3].
• The effect of brief myocardial ischemia on the expression of heat shock protein (HSP 70) was examined in an in vivo rabbit model of myocardial ischemia using Northern blotting [3].
• A single 5-min coronary occlusion doubled the expression of HSP 70 whereas four cycles of 5 min of ischemia/5 min of reperfusion resulted in a threefold increase in HSP 70 mRNA (P less than 0.001) [3].

High impact information on HSPA1A

• We propose a mechanism for the regulation of eukaryotic Hsc70 that is distinct from that of bacterial Hsp70 [4].
• In conjunction with hsp70, DnaJ proteins catalyse protein folding, protein transport across membranes and the selective disruption of protein-protein interactions [5].
• Here we show that HSP 70 binds to the surface of antigen presenting cells by a mechanism with the characteristics of a saturable receptor system [6].
• Neither S-nitrosation of caspase-3 nor induction of Hsp70 appeared to play a significant role in the antiapoptotic mechanism of *NO in oxLDL-induced endothelial apoptosis [7].
• Hsp70 is a multifunctional molecular chaperone whose interactions with protein substrates are regulated by ATP hydrolysis and ADP-ATP exchange [8].

Chemical compound and disease context of HSPA1A

• Priming neonatal calves at birth with a Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine and boosting with a DNA vaccine consisting of plasmids encoding mycobacterial antigens Hsp65, Hsp70, and Apa or the reverse prime-boost sequence induced similar levels of protection against experimental challenge with Mycobacterium bovis [9].
• Hsp70 isolated from bovine muscles showed significant protective effects against the impaired coagulation and fibrinolytic systems caused by LPS, and reduced the mortality caused by Escherichia coli and Salmonella typhimurium LPS injections significantly [10].
• Cycloheximide was also used to verify that the induction of Hsp70 takes place in lenses during heat stress [11].
• A truncated version of bovine herpesvirus-1 (BHV-1) glycoprotein IV (tgIV) was produced in a novel, non-destructive expression system based upon regulation of gene expression by the bovine heat-shock protein 70A (hsp70) gene promoter in Madin Darby bovine kidney (MDBK) cells [12].
• Using bovine retinal capillary endothelial cells (BRCEC), we investigated the effects of short-term hypoxia on DNA synthesis, phosphotyrosine induction, changes in the expression of basic fibroblast growth factor receptor (bFGFR), protein kinase C (PKC alpha), heat shock protein 70 (HSP70), and SH2-containing protein (SHC) [13].

Biological context of HSPA1A

• Five genomic clones representing three HSP70 genes of cattle were biotin labeled and independently hybridized to cattle chromosomes [14].
• Comparison of the amino acid sequence revealed an extensive sequence identity with other species of Hsp70 [1].
• This cardiac Hsp70 cDNA clone has an open reading frame of 1926 bp coding for 641 amino acids and a predicted molecular mass of 70.25 kDa [1].
• Phosphorylation resulted in the incorporation of 0.1 mol of phosphate per mol of Hsp70 [1].
• A cDNA clone for the stress-inducible 70 kDa heat-shock protein (Hsp70) has been isolated from a bovine skeletal-muscle cDNA library [15].

Anatomical context of HSPA1A

• These carbamylated proteins were shown to have similar focusing mobilities to the Hsp70 isoforms isolated from bovine skeletal muscle [15].
• The 70-kDa heat-shock protein (Hsp70) has been cloned and sequenced from bovine cardiac muscle [1].
• In the presence of ATP, bovine brain hsp70 has been shown to remove clathrin from bovine brain clathrin-coated vesicles in a rapid stoichiometric initial burst followed by slow steady-state uncoating [16].
• Recently it has been demonstrated that heat shock protein 70 (hsp70) is induced in pancreatic islet cells during prolonged exposure to interleukin 1 beta (IL-1 beta) [17].
• The ability of hsp70 isoenzymes from wild-type and mutant yeast strains to uncoat bovine brain coated vesicles was analyzed and compared with that of the brain uncoating ATPase [18].

Associations of HSPA1A with chemical compounds

• During the reaction, Hsp70 formed an acid-labile autophosphorylated intermediate, and nucleoside diphosphate-dependent dephosphorylation of the latter then occurred [8].
• These properties of Hsp70 are not identical but similar to those of NDP kinase, but are not similar to those of adenylate kinase and ATP synthase [8].
• To assess the role for hsp70 in isolated islets exposed to IL-1 beta, hsp70 was purified and introduced into cells of isolated rat pancreatic islets via the liposome technique [17].
• Our research with rats demonstrates for the first time that administration of exogeneous Hsp70 before and after LPS challenges can reduce mortality rates and modify several parameters of hemostasis and hemodynamics [10].
• Western blots determined the relative accumulation of Hsp70 in urea soluble lens fractions [11].

Regulatory relationships of HSPA1A

• In Dex-treated cultures subjected to heat shock, hsc70 antisense RNA blocked the induction of hsp70, indicating that newly synthesized RNA was targeted effectively before it became translationally active [19].

Other interactions of HSPA1A

• Another hsp70 gene (hsp70-1) was located further upstream, arranged in direct tandem with hsp70-2 [20].
• In normal diaphragmatic muscle, Hsp70 binds several proteins involved in energy metabolism including glycogen phosphorylase (PYGM) [2].
• In humans, two of the inducible Hsp70 genes are located within the human major histocompatibility complex (MHC) on 6p21.3, as a duplicated locus, 12 kb apart from each other [2].
• In addition, like the other baskets, the clathrin-MBP baskets are uncoated by hsp70 [21].
• This hsp70, isolated by affinity chromatography with RNase S-peptide-Sepharose, is referred to as the 73-kDa peptide recognition protein (prp73) [22].

Analytical, diagnostic and therapeutic context of HSPA1A

• Expression of this cDNA in a bacterial expression system produced a protein with a mobility identical with that of the inducible Hsp70 protein from bovine skeletal muscle as determined by SDS/PAGE [15].
• Southern blot analysis revealed the presence of two or three additional hsp70-related genes in the S. digitata genome [20].
• Western blot analysis with a monoclonal antibody to HSP 70 was used to compare sham and postischemic myocardial HSP 70 levels [3].
• Expression of HSP 70 was measured by Northern blotting [3].
• The induction of hsp70 mRNA and HSP70 heat-shock protein was assessed with the use of in situ hybridization and immunocytochemistry, respectively [23].

References