Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heat stress (HS) and the subsequent expression of 72 kDa heat shock protein (HSP 72) has been shown to enhance post-ischemic functional recovery and reduce infarct size. Because the synthesis of heat shock proteins involves activation of heat shock transcription factors through phosphorylation, we hypothesized that inhibition of protein kinase C (PKC) would block HS mediated protection and expression of HSP 72 in the heart. Five groups of rats were studied (1) Sham anesthetized, (2) HS group--animals were heat shocked by raising the whole body core temperature to 42 degrees C for 15 min, (3) Vehicle group--HS rats treated with 50% DMSO in saline, (4) PKC inhibitor-treated group--specific PKC antagonist, chelerythrine chloride (5 mg/kg, i.p) given 30 min prior to HS and (5) Vehicle treated control--non-HS rats treated with vehicle prior to ischemia/reperfusion. Hearts were subjected to 30 min of regional ischemia and 90 min of reperfusion 24 h after HS. Risk area was delineated by injection of 10% Evan's blue and infarct size determined using computer morphometry of tetrazolium stained sections. Infarct size (% area at risk) reduced significantly from 49.4 +/- 2.3% (n = 7) in sham to 10.0 +/- 2.5% (p < 0.01) and 9.1 +/- 3.0% in HS and vehicle treated HS groups respectively (p < 0.05) Treatment with chelerythrine prior to HS increased infarct size to 49.4 +/- 2.3% (p < 0.05). Infarct size in chelerythrine-treated non-HS ischemic/reperfused heart was 40.7 +/- 5.4%, which did not differ significantly from vehicle-treated sham group. Western blot analysis demonstrated marked increase in HSP 72 in HS groups (with or without vehicle treatment) and pretreatment with chelerythrine chloride failed to inhibit the expression of HSP 72. The results suggest that HS-induced ischemic tolerance is mediated via PKC pathway and this protection does not appear to be directly related to the expression of HSP 72 in rat heart.
Mol Cell Biochem 1999 May
PMID:Role of protein kinase C and 72 kDa heat shock protein in ischemic tolerance following heat stress in the rat heart. 1039 76

Heme oxygenase (HO)-1 is a stress protein (HSP 32) and, together with HO-2, catalyses oxidation of the heme molecule to generate carbon monoxide, a gas with vasodilatory properties, and bilirubin, an antioxidant. Right-sided heart failure (RHF) resulted in a two-fold increase in the HO-1 transcript (;1.8 kb) in the right ventricle (RV) of RHF dogs compared to that of controls. In contrast, the left ventricle showed no increase in HO-1 mRNA in RHF. The change in HO was unique to HO-1, because neither the HO-2 transcripts (;1.3 and 1.9 kb) nor the HSP 70 mRNA was altered in either ventricle. This increase in HO-1 mRNA in RV was accompanied by a two-fold increase in immunoreactive HO-1 protein, as judged by Western blot analysis, as well as by a significant increase in cGMP levels. There was, however, no significant increase in RV total nitric oxide synthase activity in RHF. Furthermore, since norepinephrine infusion also increased HO-1 transcript and protein levels, the HO-1 system probably was induced in RHF by the increased interstitial norepinephrine levels known to occur in failing myocardium. This differential regulation and induction of HO-1 gene in the failing ventricle might be one of the defense mechanisms by which the heart attempts to protect from stress caused by congestive heart failure.
J Mol Cell Cardiol 1999 Aug
PMID:Chamber-specific regulation of heme oxygenase-1 (heat shock protein 32) in right-sided congestive heart failure. 1042 55

Src family kinases are implicated in cellular proliferation and transformation. Terminally differentiated myocytes have lost the ability to proliferate, indicating the existence of a down-regulatory mechanism(s) for these mitogenic kinases. Here we show that feline cardiomyocyte lysate contains thermostable components that inhibit c-Src kinase in vitro. This inhibitory activity, present predominantly in heart tissue, involves two components acting combinatorially. After purification by sequential chromatography, one component was identified by mass and nuclear magnetic resonance spectroscopies as 5'-AMP, while the other was identified by peptide sequencing as a small heat shock protein (sHSP). 5'-AMP and to a lesser extent 5'-ADP inhibit c-Src when combined with either HSP-27 or HSP-32. Other HSPs, including alphaB-crystallin, HSP-70, and HSP-90, did not exhibit this effect. The inhibition, observed preferentially on Src family kinases and independent of the Src tyrosine phosphorylation state, occurs via a direct interaction of the c-Src catalytic domain with the inhibitory components. Our study indicates that sHSPs increase the affinity of 5'-AMP for the c-Src ATP binding site, thereby facilitating the inhibition. In vivo, elevation of ATP levels in the cardiomyocytes results in the tyrosine phosphorylation of cellular proteins including c-Src at the activatory site, and this effect is blocked when the 5'-AMP concentration is raised. Thus, this study reveals a novel role for sHSPs and 5'-AMP in the regulation of Src family kinases, presumably for the maintenance of the terminally differentiated state.
Mol Cell Biol 1999 Oct
PMID:Inhibition of src family kinases by a combinatorial action of 5'-AMP and small heat shock proteins, identified from the adult heart. 1049 Jun 24

A screen of an expression library from the fourth larval stage (L4) of the parasitic nematode Brugia malayi resulted in the identification of a 727 bp full-length cDNA with 29-40% identity to members of the small heat shock family of proteins (Bm-hsp-s1). The open reading frame encoded a protein of approximately 18 kDA (Bm-HSP-s1). An alignment of the Bm-HSP-s1 sequence with the sequences of small HSPs from vertebrate and invertebrate species demonstrated that a majority of the identity was concentrated in the central alpha-crystallin domain. Bm-HSP-s1 was constitutively produced by L4 and adult parasites and at low levels by third-stage larvae (L3), but not by first-stage larvae (microfilariae). In adult parasites, Bm-HSP-s1 was localized to the body wall muscle cells and to the cells of the hypodermis/lateral cord. Bm-HSP-s1 production was induced in adult and L3 incubated at 42 degrees C and in L3s during the developmental transition from vector-stage to vertebrate-stage parasites at 37 degrees C. Neither increased nor decreased temperatures induced Bm-HSP-s1 production in microfilariae. Nitric oxide induced low-level, transient Bm-HSP-s1 synthesis in adults, but not in microfilariae. Bm-HSP-s1 did not function as a molecular chaperone to prevent heat-induced aggregation of a test substrate. The developmentally regulated expression and inducable nature of Bm-HSP-s1 suggests that it may have a stage-restricted role in maintaining parasite homeostasis.
Mol Biochem Parasitol 1999 Nov 30
PMID:Developmentally regulated expression of a unique small heat shock protein in Brugia malayi. 1059 78

Autosomal dominant hereditary spastic paraplegia (AD-HSP) is a group of genetically heterogeneous neurodegenerative disorders characterized by pro- gressive spasticity of the lower limbs. Five AD-HSP loci have been mapped to chromosomes 14q, 2p, 15q, 8q and 12q. The SPG4 locus at 2p21-p22 has been shown to account for approximately 40% of all AD-HSP families. SPG4 encoding spastin, a putative nuclear AAA protein, has recently been identified. Here, sequence analysis of the 17 exons of SPG4 in 87 unrelated AD-HSP patients has resulted in the detection of 34 novel mutations. These SPG4 mutations are scattered along the coding region of the gene and include all types of DNA modification including missense (28%), nonsense (15%) and splice site point (26.5%) mutations as well as deletions (23%) and insertions (7.5%). The clinical analysis of the 238 mutation carriers revealed a high proportion of both asymptomatic carriers (14/238) and patients unaware of symptoms (45/238), and permitted the redefinition of this frequent form of AD-HSP.
Hum Mol Genet 2000 Mar 01
PMID:Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia. 1069 87

Mg-chelatase catalyzes the insertion of Mg into protoporphyrin and lies at the branchpoint of heme and (bacterio)chlorophyll synthesis. In prokaryotes, three genes--BchI, D and H--encode subunits for Mg-chelatase. In higher plants, homologous cDNAs for the I, D and H subunits have been characterized. Since the N-terminal half of the D subunit is homologous to the I subunit, the C-terminal portion of the pea D was used for antigen production. The antibody recognized the chloroplast D subunit and was used to demonstrate that this subunit associated with the membranes in the presence of MgCl2. The antibody immunoprecipitated the native protein and inhibited Mg-chelatase activity. Expression in Escherichia coli with a construct for the full-length protein (minus the putative transit peptide) resulted in induction of 24.5 kDa (major) and 89 kDa (minor) proteins which could only be solubilized in 6 M urea. However, when host cells were co-transformed with expression vectors for the full-length D subunit and for the 70 kDa HSP chaperonin protein, a substantial portion of the 89 kDa protein was expressed in a soluble form which was active in a Mg-chelatase reconstitution assay.
Plant Mol Biol 1999 Dec
PMID:Magnesium chelatase subunit D from pea: characterization of the cDNA, heterologous expression of an enzymatically active protein and immunoassay of the native protein. 1073 37

1. The present study was designed to examine the regional expression of HSP72/73 protein after a 7.5-min period of cerebral ischemia and to compare the distribution of HSP neurons with the localization of irreversible neuronal degeneration as analyzed by silver impregnation technique. 2. During 6-24 hr after cerebral ischemia clear-cut neuronal argyrophilia developed in several brain regions including the hippocampal hilus, nucleus reticularis thalami, and colliculi inferiores. With the exception of the hippocampal hilus, the structures which showed silver impregnability were HSP72 negative at 6-24 hr. 3. Despite the clear HSP72 expression seen in hippocampal CA1 neurons, a significant loss of these neurons was seen at 7 days after ischemia. 4. These data show that in some structures the presence of HSP72 is indicative of higher resistance of these neurons to ischemia-induced degeneration, however, the process of delayed neuronal degeneration appears to be independent of the accelerated synthesis of HSP72 seen during the early period of reflow.
Cell Mol Neurobiol 2000 Jun
PMID:Time course of brain neuronal degeneration and heat shock protein (72) expression following neck tourniquet-induced cerebral ischemia in the rat. 1078 34

Heat shock proteins (HSP's) are a family of highly conserved proteins whose expression is increased by stress. The expression of many HSP's is induced in neurons by ischemia; however, the response of the 10 kDa mitochondrial matrix HSP (HSP10) is less well characterized. To address this issue, asphyxial cardiac arrest was induced in 28 male Sprague-Dawley rats. Northern blot analysis revealed that hsp10 mRNA was increased 2.7-fold in asphyxiated rats compared to sham-operated controls. In situ hybridization demonstrated increased mRNA in the cortex, septal nuclei, hippocampus, thalamic nuclei, purkinje cell layer of the cerebellum, and isolated brainstem nuclei of asphyxiated rats. The increase of mRNA was most robust 8 h after the injury but remained increased for 72 h. These results show that hsp10 mRNA is increased following asphyxial cardiac arrest in rats and suggest that hsp10 could be another determinate of neuronal survival after ischemia.
Brain Res Mol Brain Res 2000 Jun 23
PMID:10 kD mitochondrial matrix heat shock protein mRNA is induced following global brain ischemia in the rat. 1092 56

Compared to bacteria and plants, the cold shock response has attracted little attention in mammals except in some areas such as adaptive thermogenesis, cold tolerance, storage of cells and organs, and recently, treatment of brain damage and protein production. At the cellular level, some responses of mammalian cells are similar to microorganisms; cold stress changes the lipid composition of cellular membranes, and suppresses the rate of protein synthesis and cell proliferation. Although previous studies have mostly dealt with temperatures below 20 degrees C, mild hypothermia (32 degrees C) can change the cell's response to subsequent stresses as exemplified by APG-1, a member of the HSP110 family. Furthermore, 32 degrees C induces expression of CIRP (cold-inducible RNA-binding protein), the first cold shock protein identified in mammalian cells, without recovery at 37 degrees C. Remniscent of HSP, CIRP is also expressed at 37 degrees C and developmentary regulated, possibly working as an RNA chaperone. Mammalian cells are metabolically active at 32 degrees C, and cells may survive and respond to stresses with different strategies from those at 37 degrees C. Cellular and molecular biology of mammalian cells at 32 degrees C is a new area expected to have considerable implications for medical sciences and possibly biotechnology.
J Mol Microbiol Biotechnol 1999 Nov
PMID:Cold shock response in mammalian cells. 1094 55

TLHS1 is a class I low molecular weight heat-shock protein (LMW HSP) of tobacco (Nicotiana tabacum). For a functional study of TLHS1, a recombinant DNA coding for TLHS1 with a hexahistidine tag at the amino-terminus was constructed and expressed in Escherichia coli. An expressed fusion protein, H6TLHS1, was purified using a Ni2+ affinity column and a Sephacryl S400 HR column. A polyclonal antibody against H6TLHS1 was produced to follow the fate of H6TLHS1 in E. coli. The fusion protein in E. coli maintained its solubility at a temperature of up to 90 degrees C and most of the proteins in the E. coli cell lysate with H6TLHS1 were prevented from thermally induced aggregation at up to 90 degrees C. We compared the viability of E. coli cells expressing H6TLHS1 to the E. coli cells without H6TLHS1 at a temperature of 50 degrees C. After 8 h of high temperature treatment, E. coli cells with H6TLHS1 survived about three thousand times more than the bacterial cells without H6TLHS1. These results showed that a plant class I LMW HSP, TLHS1, can protect proteins of E. coli from heat denaturation, which could lead to a higher survival rate of the bacterial cells at high temperature.
Mol Cells 2000 Oct 31
PMID:High temperature stress resistance of Escherichia coli induced by a tobacco class I low molecular weight heat-shock protein. 1110 Nov 42


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