Disease relevance of Hspb1

• Hypoxia strongly induced HO-1 mRNA without affecting HSP27 mRNA [1].
• The present study investigates the expression patterns of Hsp27 and Hsp32 in the adult rat hippocampus following whole body hyperthermia [2].
• These observations also suggest that STAT-5B/STAT-3/Hsp27/FGF-2 signaling via its involvement in the regulation of VSMC growth and motility may play an important role in the pathogenesis of vascular diseases such as restenosis after angioplasty [3].
• Alexander disease is a fatal neurological illness characterized by white-matter degeneration and the formation of astrocytic cytoplasmic inclusions called Rosenthal fibers, which contain the intermediate filament glial fibrillary acidic protein (GFAP), the small heat-shock proteins HSP27 and alphaB-crystallin, and ubiquitin [4].
• CONCLUSIONS: OFF phenomenon of thrombin-induced tolerance of the brain to edema formation may be related to HSP27 induction [5].

Psychiatry related information on Hspb1

• We propose that the expression of Hsp27 may play an important role in retinal development during a critical period of RGC functional connectivity with the superior colliculus [6].

High impact information on Hspb1

• We show that this is due to induction and phosphorylation in all adult axotomized neurons of the small heat shock protein Hsp27 and the failure of such induction in most neonatal neurons [7].
• Hsp27 upregulation and phosphorylation is required for injured sensory and motor neuron survival [7].
• In vivo delivery of human Hsp27 but not a nonphosphorylatable mutant prevents neonatal rat motor neurons from nerve injury-induced death, while knockdown in vitro and in vivo of Hsp27 in adult injured sensory neurons results in apoptosis [7].
• Transcriptional and posttranslational regulation of Hsp27 is necessary for sensory and motor neuron survival following peripheral nerve injury [7].
• 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 [8].

Chemical compound and disease context of Hspb1

• Sphingosine 1-phosphate significantly induced the accumulation of HSP27 in a pertussis toxin-sensitive manner [9].
• The levels of Hsp27 and alphaB-crystallin in C6 rat glioma cells, that had been heated at 43 degrees C for 30 min with a subsequent culture for 16 h at 37 degrees C, were markedly increased [10].
• 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 [10].
• These findings suggest that the induction of HO-1 and HSP27 during withdrawal from phenobarbital dependence may play a role in protection against glutamate toxicity [11].
• After ischemia untreated livers showed a translocation of Hsp27 towards the cytoskeleton and an increase in total Hsp27, whereas ANP preconditioning prohibited translocation but caused an augmentation of Hsp27 phosphorylation [12].

Biological context of Hspb1

• These results indicate that BDNF may down-regulate alternate cell survival pathways, including the stress-induced expression of Hsp27, and may help to explain the failure of chronic neurotrophin treatment to maintain long-term retinal ganglion cell survival [13].
• Possible involvement of phosphatidylinositol 3-kinase/Akt signal pathway in vasopressin-induced HSP27 phosphorylation in aortic smooth muscle A10 cells [14].
• Downregulation of Hsp27 via siRNA also blocked the HS-induced rescue of neonatal neurons after NGF withdrawal [15].
• Hsp27 was shown to be protective against this treatment, since HSPC cells which overexpress Hsp27 showed significantly less cell death than the parental PC12 cells [16].
• Phosphorylation of HSP27 may mediate this cytoprotection [17].

Anatomical context of Hspb1

• The results show that transient arsenite pre-treatment induces Hsp72, HO-1 and, to a lesser extent, Hsp27; it reduces H2O2-induced astrocyte death; and it causes selective activation of Akt following H2O2 [18].
• The current study detected a marked induction of a 27-kDa heat shock protein (HSP27) in the SC columns of crush-injured rat sciatic nerves [19].
• Electron microscopy and immunoelectron microscopy demonstrated that reactive Schwann cells (SCs) and the associated axons with an outgrowing profile exhibited a strong immunoreactivity to HSP27, with the former containing a greater number of bundles of intermediate filaments [19].
• These results indicate that thrombin stimulates not only the dissociation of HSP27 but also the induction of HSP27 via p38 MAPK activation in aortic smooth muscle cells [20].
• We recently reported the induction and expression of Hsp27 in a subset of retinal ganglion cells following axotomy [13].

Associations of Hspb1 with chemical compounds

• S-thiolation must occur at Cys-141, the only cysteine in rat HSP27 [21].
• SB-203580 reduced the thrombin-increased level of HSP27 mRNA [20].
• Thrombin stimulated the accumulation of HSP27 dose dependently between 0.01 and 1 U/ml and cycloheximide reduced the accumulation [20].
• Thrombin stimulated an increase in the level of HSP27 mRNA and actinomycin D suppressed the thrombin-increased mRNA level [20].
• Levels and phosphorylation states of the two small molecular chaperones, alphaB-crystallin and Hsp27, in disused rat soleus muscles were determined by Western blot analysis of extracts with antibodies recognizing each of the two proteins and their phosphorylated serine residues [22].

Physical interactions of Hspb1

• Heat shock protein (HSP27) is a cytoskeleton-interacting substrate of MAPKAPK-2 [17].

Enzymatic interactions of Hspb1

• Hsp27 is phosphorylated by mitogen-activated protein kinase-activated protein kinase 2/3, which is regulated by mitogen-activated protein (MAP) kinases [23].

Regulatory relationships of Hspb1

• The results of these experiments show that the p38 MAPK pathway is activated in GC in response to FSH in a cAMP/PKA-dependent manner, and that p38 MAPK activity is required for FSH-induced HSP-27 phosphorylation as well as rounding/aggregation in GC [24].
• 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 [25].
• In cultured aortic smooth muscle A10 cells, AVP markedly stimulated the phosphorylation of HSP27 at Ser-15 and Ser-85 [26].
• Our results suggest that ATF3- and c-Jun-induced Hsp27 expression is a novel survival response in neurons under death stress such as nerve injury [27].
• CONCLUSIONS: hsp27 phosphorylation was stimulated by low and high concentrations of cholecystokinin, both in vivo and in vitro [28].

Other interactions of Hspb1

• Thrombin stimulates dissociation and induction of HSP27 via p38 MAPK in vascular smooth muscle cells [20].
• Inactivity-induced modulation of Hsp20 and Hsp25 content in rat hindlimb muscles [29].
• Interestingly, a rapid induction of both Hsp27 and vimentin was observed in the microvasculature, suggesting that hyperthermic stress may compromise the blood-brain barrier [2].
• They also suggest that Sertoli cell micro-filaments, by virtue of their associated hsp27, may be different in composition and function from microfilaments of peritubular myoid cells and many other cell types [30].
• SB 203580 reduced the level of basal phosphorylation and blocked the increased phosphorylation of Hsp 27 after stimulation with either CCK or sorbitol [31].

Analytical, diagnostic and therapeutic context of Hspb1

• S-thiolated proteins were purified using streptavidin-agarose, and Western immunoblotting showed HSP27 was present [21].
• HSP27 mRNA and protein levels were determined using semiquantitative polymerase chain reaction, microarray (stress-toxicity, GEArray) analyses, gene sequencing, immunoblotting, and immunohistochemical analyses at 10 days and 6 months posttransplant [32].
• The authors hypothesized that HSP27 is involved in chronic allograft nephropathy (CAN), a chronic state of inflammation and stress [32].
• The cDNA was used in Northern blot analysis to estimate the relative levels of hsp27 mRNA in rat seminiferous tubule segments selected for different stages of the cycle of the seminiferous epithelium [30].
• In addition, the small heat shock protein Hsp27, with its anti-apoptotic effects, may be important for neuron survival following axotomy or trophic factor withdrawal [13].

References