Role Of Small Heat Shock Proteins Research Articles

Small heat shock proteins are induced during multiple sclerosis lesion development in white but not grey matter.

IntroductionThe important protective role of small heat-shock proteins (HSPs) in regulating cellular survival and migration, counteracting protein aggregation, preventing apoptosis, and regulating inflammation in the central nervous system is now well-recognized. Yet, their role in the neuroinflammatory disorder multiple sclerosis (MS) is largely undocumented. With the exception of alpha B-crystallin (HSPB5), little is known about the roles of small HSPs in disease. ResultsHere, we examined the expression of four small HSPs during lesion development in MS, focussing on their cellular distribution, and regional differences between white matter (WM) and grey matter (GM). It is well known that MS lesions in these areas differ markedly in their pathology, with substantially more intense blood-brain barrier damage, leukocyte infiltration and microglial activation typifying WM but not GM lesions.We analysed transcript levels and protein distribution profiles for HSPB1, HSPB6, HSPB8 and HSPB11 in MS lesions at different stages, comparing them with normal-appearing brain tissue from MS patients and non-neurological controls. During active stages of demyelination in WM, and especially the centre of chronic active MS lesions, we found significantly increased expression of HSPB1, HSPB6 and HSPB8, but not HSPB11. When induced, small HSPs were exclusively found in astrocytes but not in oligodendrocytes, microglia or neurons. Surprisingly, while the numbers of astrocytes displaying high expression of small HSPs were markedly increased in actively demyelinating lesions in WM, no such induction was observed in GM lesions. This difference was particularly obvious in leukocortical lesions covering both WM and GM areas.ConclusionsSince induction of small HSPs in astrocytes is apparently a secondary response to damage, their differential expression between WM and GM likely reflects differences in mediators that accompany demyelination in either WM or GM during MS. Our findings also suggest that during MS, cortical structures fail to benefit from the protective actions of small HSPs.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-015-0267-2) contains supplementary material, which is available to authorized users.

Small heat shock proteins (HSP12, HSP20 and HSP30) play a role in Ustilago maydis pathogenesis.

Small heat shock proteins (HSP) have multiple functions within a cell. These functions primarily include regulation of growth and survival in response to different stresses. However in some cases small HSPs have been shown to play crucial roles in microbial pathogenesis. Ustilago maydis genome also codes for a number of small HSPs. In the present study we elucidate the role of U. maydis small HSPs in the pathogenicity as well as general stress response of the fungus. Through quantitative real time PCR analysis the expression levels of small HSP genes in comparison with other HSPs were assessed both during infection of the host plant Zea mays and when the pathogen was subjected to an abiotic stress such as oxidative stress. This study revealed that contrary to other HSPs, small HSPs showed an increased level of differential expression under both the tested conditions, indicating a possible role of small HSPs in the pathogenicity and stress response of U. maydis This has been further confirmed by generation of deletion and complementation strains of three putative small HSPs.

The cardioprotective role of small heat-shock protein 20

The small HSP (heat-shock protein) HSP20 is a molecular chaperone that is transiently up-regulated in response to cellular stress/damage. Although ubiquitously expressed in various tissues, it is most highly expressed in skeletal, cardiac and smooth muscle. Phosphorylation at Ser16 by PKA (cAMP-dependent protein kinase) is essential for HSP20 to confer its protective qualities. HSP20 and its phosphorylation have been implicated in a variety of pathophysiological processes, but most prominently cardiovascular disease. A wealth of knowledge of the importance of HSP20 in contractile function and cardioprotection has been gained over the last decade. The present mini-review highlights more recent findings illustrating the cardioprotective properties of HSP20 and its potential as a therapeutic agent.

The role of small heat-shock protein αB-crystalline (HspB5) in COPD pathogenesis

BackgroundαB-crystallin (HspB5) is a chaperone whose role as a marker of innate immunity activation as well as its therapeutic potential have recently been investigated in several inflammatory diseases: multiple sclerosis, myocardial ischemia, and Guillain–Barré syndrome.AimThe aim of this study is to determine the role of αB-crystallin in chronic obstructive pulmonary disease (COPD) pathogenesis and inflammation.MaterialsPlasma levels of αB-crystallin were studied in 163 patients: 52 healthy non-COPD smokers; 20 COPD smokers in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I–II; 43 COPD smokers in GOLD stages III-IV. Forty-eight patients were diagnosed with acute inflammatory respiratory disease. The plasma levels of αB-crystallin antibodies were determined by an enzyme-linked immunosorbent assay (Calbiochem), and were confirmed with Western blotting. Tissue expression of the protein was compared in three different groups of patients: COPD smokers, COPD nonsmokers, and in patients with age-related emphysema.ResultsThe mean level of anti-αB-crystallin antibodies in non-COPD smokers was 0.291nm. In COPD smokers it was 0.352 nm and, in patients with inflammatory lung diseases, 0.433 nm. There was a statistically significant difference between COPD smokers and healthy non-COPD smokers (P = 0.010). The same could be observed comparing the group of patients with acute inflammation and non-COPD healthy smokers (P = 0.007). There was no statistically significant difference between patients with mild/moderate inflammation and those with severe COPD. Tissue detection of the protein showed that it was significantly overexpressed in COPD smokers in comparison to COPD nonsmokers and was only slightly expressed in patients with age-related emphysema.ConclusionαB-crystallin is increased in patients with inflammatory lung diseases. Though unspecific, it could be used in a panel of markers discerning COPD smokers from healthy nonsmokers. As αB-crystallin is a regulator of innate immunity and a therapeutic anti-inflammatory agent, its exact role in COPD pathogenesis and therapy should be explored further.

αB-crystallin, a small heat-shock protein, prevents the amyloid fibril growth of an amyloid β-peptide and β2-microglobulin

AlphaB-crystallin, a small heat-shock protein, exhibits molecular chaperone activity. We have studied the effect of alphaB-crystallin on the fibril growth of the Abeta (amyloid beta)-peptides Abeta-(1-40) and Abeta-(1-42). alphaB-crystallin, but not BSA or hen egg-white lysozyme, prevented the fibril growth of Abeta-(1-40), as revealed by thioflavin T binding, total internal reflection fluorescence microscopy and CD spectroscopy. Comparison of the activity of some mutants and chimaeric alpha-crystallins in preventing Abeta-(1-40) fibril growth with their previously reported chaperone ability in preventing dithiothreitol-induced aggregation of insulin suggests that there might be both common and distinct sites of interaction on alpha-crystallin involved in the prevention of amorphous aggregation of insulin and fibril growth of Abeta-(1-40). alphaB-crystallin also prevents the spontaneous fibril formation (without externally added seeds) of Abeta-(1-42), as well as the fibril growth of Abeta-(1-40) when seeded with the Abeta-(1-42) fibril seed. Sedimentation velocity measurements show that alphaB-crystallin does not form a stable complex with Abeta-(1-40). The mechanism by which it prevents the fibril growth differs from the known mechanism by which it prevents the amorphous aggregation of proteins. alphaB-crystallin binds to the amyloid fibrils of Abeta-(1-40), indicating that the preferential interaction of the chaperone with the fibril nucleus, which inhibits nucleation-dependent polymerization of amyloid fibrils, is the mechanism that is predominantly involved. We found that alphaB-crystallin prevents the fibril growth of beta2-microglobulin under acidic conditions. It also retards the depolymerization of beta2-microglobulin fibrils, indicating that it can interact with the fibrils. Our study sheds light on the role of small heat-shock proteins in protein conformational diseases, particularly in Alzheimer's disease.

OVEREXPRESSION OF ??B CRYSTALLIN IN THE GASTROINTESTINAL TRACT OF THE NEWBORN PIGLET AFTER HYPOXIA

Newborn animals are particularly sensitive to hypoxic stress. Oxygen is spared for sensitive tissues, including brain and heart. Scarce information is available concerning the molecular effects of hypoxia in the gastrointestinal tract (GIT). Moreover, stress protein expressions, including heat shock proteins (HSP), are still poorly documented in the GIT. Our objective was to determine the possible effect of hypoxia on HSP expression at birth. After western blotting, alphaB crystallin, HSP 27, and HSP 70 expressions were determined in newborn controls and piglets exposed to 1 or 4 h hypoxia (5% O2, 95% N2) allowed to recover from 1 to 68 h. Cytosol and nuclei were also separated and the extracts were tested for HSF1 and alphaB crystallin expressions. Surprisingly, alphaB crystallin was overexpressed in the stomach and colon in animals submitted to hypoxia, whereas HSP 27 and HSP 70 expression remained stable. Increases and return to basal levels in HSF1 and alphaB crystallin were simultaneously observed in the unique nuclear compartment. To our knowledge, the present study is the first to demonstrate the oxygen dependency of an HSP in the GIT, particularly in the colon in newborn piglets. The kinetics of alphaB crystallin overexpression after hypoxia parallels the activation of HSF1. This observation possibly indicates a correlation between this factor and alphaB crystallin after hypoxia. Taken together, the present results open the field of wide investigation about the specific response of this low-molecular-weight HSP and its possible involvement in pathological states in the GIT such as stomach and colon.

Thermoprotective properties of small heat shock proteins from rice, tomato and Synechocystis sp. PCC6803 overexpressed in, and isolated from, Escherichia coli

The present study forms part of a program investigating the role of small heat shock proteins (sHSPs) in the acquired and transgenic thermotolerance of the cyanobacterium Synechococcus PCC7942. The genes for three minimally related sHSPs, OsHSP from Oryza sativacytoplasm, tom111 from Lycopersicon esculentumchloroplasts, and 6803 HSP from Synechocystis sp. PCC6803, were cloned into the Escherichia coli vector pTrcHisA, so as to produce an N-terminal polyhistidine tag. The genes were transformed into E. coli and overexpressed. The tagged HSPs were purified (not completely in the case of tom111) by immobilised metal affinity chromatography. The native proteins exhibited a high degree of oligomerisation when analysed by size-exclusion chromatography. All three proteins were able to protect malate dehydrogenase (MDH) from in vitro thermal aggregation. They could also protect several soluble proteins in E. coli extracts from thermal aggregation in vitro, as well as protecting phycocyanin in extracts from Synechococcus sp. PCC7942. None of the proteins were able to protect photosystem II (measured as ΦPSII, the effective quantum fluorescence yield of PSII) of thylakoids isolated from Synechococcus sp. PCC7942 from heat damage in vitro, although in vivo, after acclimation, photosystem II did exhibit acquired thermotolerance.

The Small Heat-shock Protein IbpB from Escherichia coli Stabilizes Stress-denatured Proteins for Subsequent Refolding by a Multichaperone Network

The role of small heat-shock proteins in Escherichia coli is still enigmatic. We show here that the small heat-shock protein IbpB is a molecular chaperone that assists the refolding of denatured proteins in the presence of other chaperones. IbpB oligomers bind and stabilize heat-denatured malate dehydrogenase (MDH) and urea-denatured lactate dehydrogenase and thus prevent the irreversible aggregation of these proteins during stress. While IbpB-stabilized proteins alone do not refold spontaneously, they are specifically delivered to the DnaK/DnaJ/GrpE (KJE) chaperone system where they refold in a strict ATPase-dependent manner. Although GroEL/GroES (LS) chaperonins do not interact directly with IbpB-released proteins, LS accelerate the rate of KJE-mediated refolding of IbpB-released MDH, and to a lesser extent lactate dehydrogenase, by rapidly processing KJE-released early intermediates. Kinetic and gel-filtration analysis showed that denatured MDH preferentially transfers from IbpB to KJE, then from KJE to LS, and then forms a active enzyme. IbpB thus stabilizes aggregation-prone folding intermediates during stress and, as an integral part of a cooperative multichaperone network, is involved in the active refolding of stress-denatured proteins.