Disease relevance of Hspb1

• HSP-25 expression is increased in the proximal tubule cells in the outer stripe of the outer medulla postobstruction, prior to, and 24 h after ischemia [1].
• In several tissues the amount of hsp25 exceeds that accumulating in NIH 3T3 fibroblasts in response to heat stress. hsp25, like alpha B crystallin, exists in a highly aggregated form in the eye lens [2].
• Native phosphorylated mouse small heat shock protein hsp25 from Ehrlich ascites tumor cells was isolated and the in vivo phosphorylation sites of the protein were determined [3].
• This study was conducted to assess the expression pattern of hsp27 in a panel of different ichthyoses [4].
• Hsp27 expression was reduced in bullous ichthyosiform erythroderma and annular epidermolytic ichthyosis, and absent in X-linked recessive ichthyosis (1/3 patients) and congenital hemidysplasia with ichthyosiform nevus and limb defects syndrome (1/1) [4].

Psychiatry related information on Hspb1

• Our results indicate that TNF-alpha induces in cardiomyocytes transiently gene expression for cytoprotective molecules like HSP-27, HSP-70 and ubiquitin, suggesting these stress proteins to participate in subsequent defense mechanisms, for example in postischemic myocardial recovery [5].

High impact information on Hspb1

• Heat shock proteins appear to have been involved in innate immune responses since the emergence of phagocytes in early multicellular organisms and to have been commandeered for adaptive immune responses with the advent of specificity [6].
• Heat shock results in an arrest of most transcription and translation; subsequently, expression of a limited set of genes, the heat shock genes, precedes the overall reactivation of cellular genome [7].
• Heat shock protein 70 promotes cell survival by inhibiting lysosomal membrane permeabilization [8].
• Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity [9].
• Heat-shock proteins protect cells from monocyte cytotoxicity: possible mechanism of self-protection [10].

Chemical compound and disease context of Hspb1

• Twelve hereditary and acquired skin diseases associated with an ichthyotic phenotype and 2 corresponding mouse models were investigated by immunohistochemistry on formalin-fixed paraffin-embedded tissue, using a monoclonal antibody specific for hsp27 [4].
• In this study, we examined the expression of Hsp25 (the rodent homologue to human Hsp27) and Hsp70 in 3 different rodent tumors (a mouse breast carcinoma, a rat sarcoma, and a rat lymphoma maintained by subcutaneous passages) treated in vivo with doxorubicin (DOX) and lovastatin (LOV) [11].
• Induction of Hsp27, alphaB crystallin and Hsp70 in the liver and adrenal glands of heat-stressed (42 degrees C for 20 min) rats was also enhanced by prior injection of curcumin (20 mg/kg body weight) [12].
• To examine whether Hsp27 would ameliorate acute pancreatitis, we generated transgenic mice overexpressing human Hsp27 (huHsp27) or Hsp27 with the phosphorylatable residues Ser(15,78,82) mutated to aspartic acid (huHsp27-3D) to mimic phosphorylation or to alanine (huHsp27-3A), which is nonphosphorylatable [13].
• Heat shock protein 27 increases after androgen ablation and plays a cytoprotective role in hormone-refractory prostate cancer [14].

Biological context of Hspb1

• When RIF cells were transfected with inducible Hspa or Hspb1, both radioresistance measured by clonogenic assays and a reduction of apoptosis were detected [15].
• The dominant negative Nfkb1a inhibited Hspb1-mediated SOD2 gene expression [16].
• In addition, Hspb1-mediated radioresistance was blocked by dominant negative Nfkb1a transfection [16].
• IL-11 induced a shift of hsp25 to Triton x-100 insoluble fractions containing cytoskeletal elements, which was not associated with altered hsp25 phosphorylation [17].
• Consistent with the downregulation of Hsp25, for example, a significantly lower glutathione (GSH)/glutathione disulfate (GSSG) ratio was associated with the decreased activity, but not protein content, of glucose 6-phosphate dehydrogenase [18].

Anatomical context of Hspb1

• IL-11 induction of hsp72 and hsp25 was determined by immunoblot in IEC-18 crypt and young adult mouse colon colonic epithelial cells [17].
• In human keratinocyte cultures, inhibitors of p38MAPK prevented PV IgG-induced phosphorylation of HSP27 and, more importantly, prevented the early cytoskeletal changes associated with loss of cell-cell adhesion [19].
• Mutant SOD1 co-precipitated and co-localized with Hsp25 in neurons and astrocytes [20].
• In the present study, a high concentration of H2O2 was found to induce DNA fragmentation in L929 mouse fibroblast cells, and HSP25 overexpression attenuated this phenomenon [21].
• These findings tentatively suggest that cadmium-induced nephrotoxicity results, in part, from glomerular contraction due to p38 MAP kinase/HSP25 signaling-dependent contraction of mesangial cells [22].

Associations of Hspb1 with chemical compounds

• The IL-11 effect on hsp25 distribution was characterized by analysis of Triton x-100 insoluble fractions, 2-D isoelectric focusing gels, and confocal microscopy [17].
• Furthermore, mutation of phosphorylation sites of hsp27 renders the interaction resistant to H(2)O(2) and arachidonic acid [23].
• Heat shock protein 25 or inducible heat shock protein 70 activates heat shock factor 1: dephosphorylation on serine 307 through inhibition of ERK1/2 phosphorylation [24].
• The cadmium-induced responses were inhibited by the specific p38 MAP kinase inhibitor SB-203580, and cadmium-induced phosphorylation of HSP25 was inhibited by expression of a dominant-negative p38 MAP kinase mutant [22].
• Exposure of isolated rat glomeruli to cadmium also resulted in contraction and increased HSP25 phosphorylation [22].

Physical interactions of Hspb1

• HSP25 binds to kinase-active PKCdelta to inhibit its kinase activity and translocation to the membrane, which results in reduced cell death [25].
• Examination of two deletion mutants of hsp110 demonstrated that its peptide-binding domain is required for interaction with hsp25, but not with hsc70 [26].
• Furthermore, Hsp25 formed a complex with Akt, a member of PI-3 kinase pathway that prevents neuronal cell death [27].
• Heat shock-induced dendritic cell maturation is coupled by transient aggregation of ubiquitinated proteins independently of heat shock factor 1 or inducible heat shock protein 70 [28].
• Heat shock protein 70 binding inhibits the nuclear import of apoptosis-inducing factor [29].

Enzymatic interactions of Hspb1

• Furthermore, native hsp25 was phosphorylated by the endogenous kinase(s) in a cell-free system as well as recombinant hsp25 was phosphorylated in vitro by protein kinase C and catalytic subunit of cAMP-dependent protein kinase [3].
• Furthermore, endogenous MK5 is not able to phosphorylate Hsp27 in vitro and in vivo [30].

Regulatory relationships of Hspb1

• IL-11 induces hsp25 in an intestinal epithelial-specific manner that significantly preserves cellular viability in the presence of monochloramine [17].
• The introduction of Hsp25 cDNA stimulated the accumulation of p21 transcripts through transcriptional but not posttranscriptional regulation in these cells [31].
• Phosphatidylinositol 3-kinase/Akt plays a role in sphingosine 1-phosphate-stimulated HSP27 induction in osteoblasts [32].
• A combination of SP600125 and p38 MAP kinase inhibitor such as SB203580 and PD169316 additively reduced the ET-1-stimulated accumulation of HSP27 [33].
• Heat shock and 5-azacytidine inhibit nitric oxide synthesis and tumor necrosis factor-alpha secretion in activated macrophages [34].

Other interactions of Hspb1

• From the above results, we suggest for the first time that reduced oxidative damage by HSP25 was due to MnSOD-mediated downregulation of ERK1/2 [21].
• p38 MAPK/HSP25 signaling mediates cadmium-induced contraction of mesangial cells and renal glomeruli [22].
• Increased expression of Tnf and Il1b resulting from Hspb1 overexpression was detected by RT-PCR [16].
• The inducible Hspa transfectant showed a more pronounced adaptive response than the Hspb1 transfectant [15].
• To further elucidate the exact relationship between induction of SOD2 and Nfkb activation, a dominant negative I-kBalpha (now known as Nfkb1a) construct was transfected into Hspb1-overexpressing cells [16].

Analytical, diagnostic and therapeutic context of Hspb1

• The shift was not paralleled by increased hsp25 co-localization with F-actin by confocal microscopy [17].
• In this study, the interaction between p38 and hsp27 was visualized in single living L929 cells using fluorescence resonance energy transfer technology, while their association with Akt was examined by immunoprecipitation analysis [23].
• We also investigated the sub-cellular localization of HSP25 by fluorescence immunocytochemistry [35].
• To analyze the role of heat shock response in the cochleae, we induced major heat shock proteins, Hsp70, Hsp90, and Hsp27 by perfusion of hot saline into the middle ear cavity (called 'local heat shock') in guinea pigs [36].
• Northern blot analysis of heat shock protein 27-related transcript expression revealed that, while HSP 27 expression (850-nucleotide transcript) was induced by heat shock alone, the expression of a smaller transcript was facilitated by estrogen treatment prior to heat shock [37].

References