Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chymotryptic digestion of bovine brain uncoating ATPase produced a 60-kDa fragment that was subsequently proteolyzed to 44 kDa. Loss of clathrin cage uncoating activity paralleled the conversion of the intact 70-kDa enzyme to the 60-kDa fragment, while clathrin binding activity was lost as the 60-kDa fragment was degraded to 44 kDa. This 44-kDa fragment has been purified to homogeneity and characterized as a clathrin-independent ATPase. The 44-kDa ATPase domain has been localized within the intact enzyme by the use of amino-terminal specific antibodies. This localization relates to the conserved nature of the 70-kDa heat shock protein family, of which bovine brain uncoating ATPase is a constitutively expressed member.
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PMID:The ATPase core of a clathrin uncoating protein. 302 66

Cyclic nucleotide-dependent vascular relaxation is associated with increases in the phosphorylation of a small heat shock protein (HSP), HSP20. An increase in phosphorylation of another small HSP, HSP27, is associated with impaired cyclic nucleotide-dependent vascular relaxation. Expression of HSPs is altered by exposure to several types of cellular stress in vitro. To determine if behavioral stress in vivo alters vascular expression and phosphorylation of the small HSPs and cyclic nucleotide-dependent vascular relaxation, borderline hypertensive rats were stressed by restraint and exposure to air-jet stress 2 h/day for 10 days or remained in their home cage. Stress impaired relaxation of aorta to forskolin, which activates adenylyl cyclase, and sodium nitroprusside, which activates guanylyl cyclase. This was associated with an increase in the aortic expression and phosphorylation of HSP27, which was localized to the vascular smooth muscle, but a decrease in the amount of phosphorylated (P)-HSP20. To determine if P-HSP27 inhibits phosphorylation of HSP20, P-HSP27 was added to a reaction mixture containing recombinant HSP20 and the catalytic subunit of cAMP-dependent protein kinase. P-HSP27 inhibited phosphorylation of HSP20 in a concentration-dependent manner. These data demonstrate that P-HSP27 can inhibit phosphorylation of HSP20. The increase in P-HSP27 and decrease in P-HSP20 were associated with reduced cyclic nucleotide-dependent vascular smooth muscle relaxation in response to behavioral stress in vivo, an effect similar to that observed previously in response to cellular stress in vitro.
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PMID:Stress causes decrease in vascular relaxation linked with altered phosphorylation of heat shock proteins. 1093 37

Several studies have suggested a positive correlation between heat shock protein (hsp) expression and tumor immunogenicity. Independently, many studies have shown that hsp purified from tumors can be used as a tumor-specific vaccine. In this study, we have explored the connection between hsp expression and anti-tumor immunity by transducing murine CT26 colon carcinoma cells with the cDNA of a major hsp, i.e. hsp110. We have shown that over-expression of hsp110 has no effect on CT26 tumor cell growth in vitro, and does not inhibit their anchorage-independent growth capacity. However, in situ, hsp110 over-expressing CT26 tumor (CT26-hsp110) grew at a significantly reduced rate as compared to the wild-type CT26 tumor in immunocompetent mice. Moreover, immunization of mice with inactivated CT26-hsp110 cells significantly inhibited the growth of wild-type CT26 tumor. This immunity was associated with an increased frequency of tumor-specific T cells after vaccination. An in vivo antibody depletion assay demonstrated that inactivated CT26-hsp110 cells elicited anti-tumor responses involving CD8(+) T cells and natural killer (NK) cells, but not CD4(+) T cells. Lastly, the effect of the addition of granulocyte-macrophage colony stimulating factor (GM-CSF) to these vaccine formulations was determined. Mice immunized with irradiated CT26-hsp110 cells combined with GM-CSF-producing bystander cells revealed a complete inhibition of CT26 tumor growth, indicating a synergy between inactivated CT26-hsp110 vaccine activity and GM-CSF. These observations demonstrate that manipulation of hsp110 expression in tumors, specifically when combined with GM-CSF, represents a potentially powerful approach to cancer vaccine formulation.
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PMID:Hsp110 over-expression increases the immunogenicity of the murine CT26 colon tumor. 1211 Nov 19

Herpes simplex virus (HSV) is a large, enveloped DNA virus that replicates in the nucleus and is assembled in the cytoplasm to the mature infectious virion. In this study, we present evidence that, in HSV-2-infected cells, some tegument proteins (UL46 and VP16) and newly synthesized nucleocapsids accumulate in a juxtanuclear domain sharing characteristics with aggresomes, cellular structures formed in response to misfolded proteins [J. Cell Biol. 146 (1999) 1239, J. Cell Biol. 143 (1998) 2010]. The juxtanuclear domains (aggresome-like structures) induced by HSV-2 infection localize to the microtubule organizing center (MTOC) where the clustering mitochondria, Golgi-derived vesicles, and cellular chaperones including heat shock protein (Hsp)40 and Hsp70 were recruited. Formation of aggresome-like structures was blocked by the presence of microtubule-disassembling drug nocodazole, indicating that microtubule-dependent transport may be involved in the accumulation of viral and cellular proteins at these sites in HSV-2-infected cells. These features are similar to those governing the formation of aggresomes. In contrast to aggresomes, however, the vimentin cage surrounding the MTOC was not observed with the aggresome-like structures in HSV-2-infected cells, and the maintenance of these structures required an intact microtubular network. Disruption of the aggresome-like structures by nocodazole treatment led to a low but consistent effect (10-fold decrease) on the production of intracellular infectious particles. These results suggest that aggresome-like structures do not play a critical but augmentary role in HSV-2 replication.
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PMID:Formation of aggresome-like structures in herpes simplex virus type 2-infected cells and a potential role in virus assembly. 1535 May 46

Effects of heat stress on the recovery of atrophied soleus muscle were studied in rats. Ten-week-old male Wistar rats were randomly divided into cage control (CC) and 5-day hindlimb suspension group (HS). The half of the rats in group HS was exposed to heat stress (41 degrees C for 60 min) in an incubator immediately after the hindlimb suspension (HS-H) and the other group of rats was not heat stressed (HS-C) prior to 10 days of ambulation recovery. One group of cage control rats (CH) was also exposed to heat similarly. The soleus muscles were dissected at four time points, i.e., immediately after the suspension (or heat stress), and 3, 5, and 10 days after the recovery (n=8 per group at each time point). The absolute wet weight and water and protein content of whole soleus muscle in group HS-C were approximately 36, 27, and 8 mg less than CC (p <0.05). Thus, the percentage contribution of water and protein loss to the decrease in muscle weight was 75 and 22%, respectively. Although water content, as well as muscle weight, was elevated within 3 days, the increase of protein was delayed. Heat exposure prior to recovery accelerated the increase in protein content even in the control group. These phenomena were closely associated with 72-kD heat shock protein (HSP72) content. It is suggested that heat stress applied at the end of hindlimb unloading facilitated the recovery of atrophied soleus muscle of rat, through possibly HSP72-related events of protein metabolism. The data also indicated that the combination of heat and mechanical stress evoked larger and long lasting HSP72 response than does heat or mechanical stress alone.
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PMID:Heat stress facilitates the recovery of atrophied soleus muscle in rat. 1554 Dec 6

The antitumor agent doxorubicin was covalently bound and selectively released in a pH dependent manner from the interior surface of a genetically modified small heat shock protein (Hsp) cage.
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PMID:Selective attachment and release of a chemotherapeutic agent from the interior of a protein cage architecture. 1565 65

A biomimetic approach has been used to develop an artificial hydrogenase that catalyses the efficient reduction of protons producing hydrogen gas. Analogous to the unique biological metal clusters found in hydrogenase enzymes, the engineered active sites are small, well-defined Pt clusters deposited on the interior of a heat shock protein cage architecture with stoichiometries of 150 to 1000 Pt per protein cage. The proton reduction reaction is driven by visible light through a coupled reaction with Ru(bpy)3(2+) and methyl viologen as an electron-transfer mediator. Hydrogen production rates are comparable to those of hydrogenase on a per protein basis and exceed production rates of other reported Pt-based catalysts. These results demonstrate the utility of a biomimetic approach toward addressing the needs of hydrogen production.
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PMID:Biomimetic synthesis of a H2 catalyst using a protein cage architecture. 1627 73

The use of doxorubicin, a highly effective antitumor antibiotic, is limited by a dose-dependent cardiotoxicity. The purpose of this study was to determine whether chronic exercise training (ET) prior to doxorubicin treatment would preserve cardiac function and reduce myocardial oxidative stress following treatment. Rats were exercise trained on a motorized treadmill or confined to sedentary cage activity for 12 weeks, then administered an intraperitoneal injection of doxorubicin (15 mg/kg) or 0.9% saline. Five days following the injections, hearts were isolated and Langendorf perfused to assess cardiac function and then processed for biochemical analyses. Doxorubicin treatment induced significant inotropic, lusitropic, and chronotropic cardiac dysfunction, reduced coronary flow, and increased cardiac lipid peroxidation in the sedentary animals. Doxorubicin treatment was also associated with a decrease in cardiac manganese superoxide dismutase protein expression and an increase in heat shock protein-72 (Hsp72) compared with saline-treated animals. Exercise training attenuated doxorubicin-induced cardiac dysfunction, and lipid peroxidation, and led to a greater cardiac expression of Hsp72 compared with the sedentary animals. The results of this study demonstrate for the first time that chronic exercise training before doxorubicin treatment protects against cardiac dysfunction following treatment, and provide evidence for a sustained increase in myocardial Hsp72 following exercise training and doxorubicin treatment in vivo.
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PMID:Exercise training attenuates acute doxorubicin-induced cardiac dysfunction. 1649 54

The majority of previous work examining stress responses has been done in males. Recently, it has become clear that the impact of stressor exposure is modulated by sex. One stress response that may be affected by sex is the induction of intracellular heat shock protein (HSP) 72, which is a stress- responsive molecular chaperone that refolds denatured proteins and promotes cellular survival. The following study compared HSP72 in males and females and also examined whether the estrous cycle altered HSP72 induction in females. We hypothesized that females compared with males would have a constrained HSP72 response after an acute stressor and that the stress-induced HSP72 response in females would fluctuate with the estrous cycle. Male and female F344 rats were either left in their home cage or exposed to acute tail-shock stress (8-10/group). Immediately following stressor, trunk blood was collected and tissues were flash frozen. Vaginal smear and estrogen enzyme immunoassay were used to categorize the phase of estrous. Results show that female rats had a greater corticosterone response than males, that both males and females exhibit a stress-induced release of progesterone, and that males and females had equal levels of stress-induced circulating norepinephrine. Sexual dimorphism of the HSP72 (ELISA) response existed in pituitary gland, mesenteric lymph nodes, and liver such that female rats had an attenuated HSP72 response compared with males after stress. The adrenal glands, spleen, and heart did not exhibit sexual dimorphism of the HSP72 response. The estrous cycle did not have a significant effect on basal or stress-induced HSP72 in females.
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PMID:Sexual dimorphism of the intracellular heat shock protein 72 response. 1669 Jul 92

DNA vaccines encoding heat shock protein (hsp)-capturing, chimeric peptides containing antigenic determinants of the tumor-associated Ag (TAA) gp70 (an envelope protein of endogenous retrovirus) primed stable, specific, and tumor-protective CD8 T cell immunity. Expression of gp70 transcripts was detectable in most normal tissues but was particularly striking in some (but not all) tumor cell lines tested (including the adenocarcinoma cell line CT26). An approximately 200 residue gp70 fragment or its L(d)-binding antigenic AH1 peptide cloned in-frame behind an hsp-capturing (cT(272)) or noncapturing (T(60)) N-terminal large SV40 tumor Ag sequence was expressed as either hsp-binding or -nonbinding chimeric Ags. Only hsp-capturing, chimeric fusion proteins were expressed efficiently in transfected cell lines and primed TAA-specific CD8 T cell immunity. This immunity mediated protection in the CT26 and mKSA models. A vaccination strategy based on delivering antigenic, hsp-associated TAA fragments can thus prime protective CD8 T cell immunity even if these TAA are of low intrinsic immunogenicity.
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PMID:Priming protective CD8 T cell immunity by DNA vaccines encoding chimeric, stress protein-capturing tumor-associated antigen. 1684 60


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