Disease relevance of Hspd1

• These data suggest that decreased Hsp60 expression and subsequent decline of IGF-1R signaling may be a fundamental mechanism underlying the development of diabetic cardiomyopathy [1].
• The independent effect of insulin and hyperglycemia on Hsp60 was investigated in primary cardiomyocytes [2].
• Hsp10 and GroES are members of the chaperonin 10 family of molecular chaperones, and GroEs is necessary for the optimal activity of GroEL, a member of the chaperonin 60 family and the E. coli homologue of mycobacterial hsp65 [3].
• In the present study we report the occurrence of chaperonins, cpn10 and cpn60, in Chromatium vinosum and rat hepatocytes, using specific polyclonal antibodies in conjunction with the protein A-gold immunocytochemical technique [4].
• Therefore, in contrast to the accepted concept that cross-reactive T cell recognition of foreign and self antigens might induce aggressive autoimmune disease, we propose that cross-reactivity between bacterial and self hsp60 might also be used to maintain a protective self-reactive T cell population [5].

Psychiatry related information on Hspd1

• Examination of antibodies raised against HSP65 showed no overt differences in plasma levels following chronic alcohol consumption, and liver changes as assessed by histology were mild [6].

High impact information on Hspd1

• Moreover, arthritic rats in the late phase of AA also raised vigorous T cell responses to those carboxy-terminal determinants within self(rat) hsp65 (Rhsp65) that correspond in position to the above BCTD [7].
• Hsp65 shares 48% amino acid identity with mammalian hsp60, which is expressed at elevated levels in inflamed synovia [5].
• We previously described nine major histocompatibility complex class II-restricted epitopes in mycobacterial hsp65 recognized by Lewis rat T cells [5].
• Lymphocytes isolated from the spinal cord infiltrate were compared with cells from the popliteal lymph nodes with respect to frequency of cells responding to basic protein (BP), mycobacterium tuberculosis (MT), the 65-kD heat shock protein (hsp65), allogeneic brown norway spleen cells, and concanavalin A [8].
• Water immersion stress induces heat shock protein 60 expression and protects against pancreatitis in rats [9].

Chemical compound and disease context of Hspd1

• Because phlorizin does not alter insulin secretion, Hsp60 expression was modulated by insulin and not by hyperglycemia [2].
• NCM were infected with adenoviral vectors expressing mPHGPx, cPHGPx, HSP60/10, or an empty control (Adv-) and submitted to 8 h of ischemia followed by 16 h of reoxygenation. mPHGPx infection led to a 40% decrease in malondialdehyde and 4-hydroxy-2(E)-nonenal following I/R (p<.05) [10].
• In Sprague-Dawley rats maintained under propofol anaesthesia, proteomic or Western blot analysis revealed a progressive augmentation of HSP60 expression in the RVLM after intravenous administration of Escherichia coli lipopolysaccharide (30 mg kg(-1)) [11].
• 4. The effect of maleate may be partially non-specific and involve a great variety of proteins, but seems to be restricted to selected tissues because alpha 1 subunit Na+,K(+)-ATPase and hsp60 protein amounts were not significantly modified in livers from rats developing Fanconi syndrome [12].
• However the effects of caerulein, melatonin or hyperthermia preconditioning on mRNA signal for HSP60 in the pancreatic acinar cells has not been examined yet [13].

Biological context of Hspd1

• These data indicate that Hsp10 and Hsp60 can modulate IGF-1R signaling through post-translational modification [1].
• These findings suggest that insulin deficiency is a novel mechanism that leads to downregulation of Hsp60 in diabetic muscle tissues [2].
• Nucleotide sequence of rat hsp60 (chaperonin, GroEL homolog) cDNA [14].
• Hsp10 and Hsp60 modulate Bcl-2 family and mitochondria apoptosis signaling induced by doxorubicin in cardiac muscle cells [15].
• We propose that, like the protein-folding machinery of prokaryotes, mitochondrial cpn60 requires a cochaperonin for full biological function [16].

Anatomical context of Hspd1

• In animal models of diabetes, diabetic myocardium is associated with decreased abundance of Hsp60, increased ubiquitination of IGF-1R, and lower level of IGF-1R protein [1].
• Similar changes of Hsp60 and IGF-1 receptor were observed in the skeletal muscle of STZ-induced diabetic rats [2].
• Methylprednisolone-induced expression of mitochondrial heat shock protein 60 protects mitochondrial membrane potential in the hypoxic rat liver [17].
• Western immunoblotting analysis of rat pancreas homogenates has shown that antibodies against cpn10, cpn60 and hsp70 protein recognize single protein bands of 25 kDa, 60 kDa and 70 kDa, respectively [18].
• Chaperonin 10 and cpn60 were located in the endoplasmic reticulum, Golgi apparatus, condensing vacuoles and secretory granules [18].

Associations of Hspd1 with chemical compounds

• In contrast, the abundance of Hsp60 was not affected by high concentration of glucose in these cells [2].
• In the phlorizin-treated diabetic rats, myocardial Hsp60 was lower than that of the normal controls [2].
• In the streptozotocin (STZ)-induced diabetic rat, downregulation of Hsp60 and IGF-1 receptor occurred 4 days after induction of diabetes [2].
• Antisense Hsp60 reduced the abundance of endogenous Hsp60 in cardiomyocytes and amplified the cytotoxicity of doxorubicin [15].
• Thus, like the bacterial homologue, mitochondrial cpn10 facilitates a K(+)- and Mg.ATP-dependent discharge of unfolded (or partially folded) ribulose bisphosphate carboxylase from bacterial chaperonin 60 (cpn60; also known as groEL) [16].

Physical interactions of Hspd1

• Hsp60 interacted with Bcl-xl and Bax in the cardiomyocytes in vivo [15].

Regulatory relationships of Hspd1

• Inhibition of adjuvant-induced arthritis by interleukin-10-driven regulatory cells induced via nasal administration of a peptide analog of an arthritis-related heat-shock protein 60 T cell epitope [19].
• We conclude that HSP60 redistributed from mitochondrion to cytosol in the RVLM confers neuroprotection against fatal cardiovascular depression during endotoxaemia via reduced activation of the cytochrome c-caspase-3 cascade of apoptotic signalling through enhanced interactions with mitochondrial or cytosolic Bax or Bcl-2 [11].
• We demonstrated that water-immersion stress or TRH administration specifically induced HSP60, although preinduction of this protein did not show a cytoprotective function in the small intestinal mucosa [20].
• Moreover, feeding Hsp65/SBTI resulted in a lower number of both spleen and mesenteric lymph node (MLN) cells expressing the costimulatory molecule CD80 (B7-1) [21].
• Our findings suggest the presence of mycobacterial hsp65 determinants that selectively trigger AA-regulating T cells and illustrate that cathepsin D may be used as an experimental tool to generate such determinants [22].

Other interactions of Hspd1

• Bacterial and mitochondrial cpn10 compete for a common saturable site on bacterial cpn60 [16].
• A comparison of steady-state levels of mitochondrial enzyme activity [cytochrome c oxidase (CYTOX)] with chaperonin levels [the heat-shock protein HSP60, the glucose-regulated protein GRP75 (mtHSP70)] in striated muscles possessing a wide range of oxidative capacities revealed a proportional expression between the two [23].
• In primary cultures and brain tissue, the increased Hsp70 mRNA levels were still more than 500-fold less than constitutive Hsc70 mRNA and 50-fold less than Hsp60 levels [24].
• In summary, endothelial cells stressed by high temperature or certain cytokines, eg, TNF-alpha, express hsp60 in the cytoplasm and on their surfaces, and these cells were susceptible to complement-dependent lysis by hsp60-specific antibody [25].
• These results indicate that overexpression of PHGPx provides protection against damage resulting from simulated I/R injury, particularly in the mitochondria, and that the combination of mPHGPx and HSP60/10 imparts an added protective effect [10].

Analytical, diagnostic and therapeutic context of Hspd1

• Immunofluorescence studies on rat pancreatic tissue revealed a strong positive signal in the apical region of the acinar cells for cpn10 and cpn60, while an immunoreaction was detected at the juxtanuclear Golgi region with the anti-hsp70 antibody [18].
• As demonstrated by quantitative evaluations, the immunolabeling for cpn10 and cpn60 in C vinosum cells was associated primarily with the bacterial cell envelope [4].
• On the other hand, using the post-embedding immunoelectron microscopy technique cpn10 and cpn60 were localized specifically in liver mitochondria and peroxisomes [4].
• Peptide-induced nasal tolerance for a mycobacterial heat shock protein 60 T cell epitope in rats suppresses both adjuvant arthritis and nonmicrobially induced experimental arthritis [26].
• Treatment of adjuvant-induced arthritis by oral administration of mycobacterial Hsp65 during disease [21].

References