Protein kinase A-catalyzed phosphorylation of heat shock protein 60 chaperone regulates its attachment to histone 2B in the T lymphocyte plasma membrane

Khan, Islam Ullah; Wallin, Reidar; Gupta, Radhey S.; Kammer, Gary M.

doi:10.1073/pnas.95.18.10425

Cited by 107 publications

(67 citation statements)

References 54 publications

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“…Recently, the presence of histones in both the cytoplasm and the nucleus has been reported (3, 30 -34), and secretion of histone proteins into extracellular milieu was also observed (35)(36)(37)(38). Now it is clear that histone proteins are present in both the cytoplasm and the nucleus of rapidly regenerating or transcriptionally active cells such as stomach epithelial cells.…”

Section: Discussionmentioning

confidence: 93%

Pepsin-Mediated Processing of the Cytoplasmic Histone H2A to Strong Antimicrobial Peptide Buforin I

Kim

Yoon

Minn

et al. 2000

The Journal of Immunology

111

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The intestinal epithelium forms a first line of innate host defense by secretion of proteins with antimicrobial activity against microbial infection. Despite the extensive studies on the antimicrobial host defense in many gastrointestinal tracts, little is known about the antimicrobial defense system of the stomach. The potent antimicrobial peptide buforin I, consisting of 39 aa, was isolated recently from the stomach tissue of an Asian toad, Bufo bufo gargarizans. In this study we examined the mechanism of buforin I production in toad stomach tissue. Buforin I is produced by the action of pepsin isozymes, named pepsin Ca and Cb, cleaving the Tyr39-Ala40 bond of histone H2A. Immunohistochemical analysis revealed that buforin I is present extracellularly on the mucosal surface, and unacetylated histone H2A, a precursor of buforin I, is localized in the cytoplasm of gastric gland cells. Furthermore, Western blot analysis showed that buforin I is also present in the gastric fluids, and immunoelectron microscopy detected localization of the unacetylated histone H2A in the cytoplasmic granules of gastric gland cells. The distinct subcellular distribution of the unacetylated histone H2A and the detection of the unacetylated buforin I both on the mucosal surface and in the lumen suggest that buforin I is produced from the cytoplasmic unacetylated histone H2A secreted into the gastric lumen and subsequently processed by pepsins. Our results indicate that buforin I along with pepsins in the vertebrate stomach may contribute to the innate host defense of the stomach against invading microorganisms.

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Section: Discussionmentioning

confidence: 93%

Pepsin-Mediated Processing of the Cytoplasmic Histone H2A to Strong Antimicrobial Peptide Buforin I

Kim

Yoon

Minn

et al. 2000

The Journal of Immunology

111

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“…Evidence points to an additional surface location of hsp60 proteins in endothelial cells. 34 Hsps may also be released from dead cells and evoke inflammatory reactions in the vessel wall. 26a,35 Preexisting antibodies could react with these surfaceexposed or released hsp60 components, causing further endothelial and macrophage injury and perpetuating the progress of atherosclerotic lesions.…”

Section: Discussionmentioning

confidence: 99%

Association of Serum Antibodies to Heat-Shock Protein 65 With Carotid Atherosclerosis

et al. 1999

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Background-Previous work has proved that increased titers of antibodies against heat-shock protein (hsp) 65 are associated with atherosclerotic lesions independently of other established risk factors. The present follow-up study was designed to further scrutinize the association of hsp antibodies and atherosclerosis and evaluate the possible predictive value of these antibodies for the development and/or progression of lesions in the same population. Methods and Results-A total of 750 subjects 45 to 74 years old were recruited, and the rate of participation was 93.6%; 58 subjects died between 1990 and 1995. All participants were subjected to determination of serum antibodies against hsp65 and sonography to assess carotid atherosclerotic lesions and evaluate other risk factors, ie, age, sex, body mass index, blood cholesterol, apolipoprotein B, apolipoprotein A, triglycerides, lipoprotein(a), fibrinogen, leukocyte number, antithrombin III, ESR, ferritin, hypertension, smoking, and diabetes mellitus. Our data show that hsp65 antibody titers in the population emerged as highly consistent over a 5-year observation period (rϭ0.78, PϽ0.0001). Titers were significantly elevated in subjects with progressive carotid atherosclerosis and correlated with intima/media thickness. Multiple linear regression analysis documented these associations to be independent of age, sex, and other risk factors. Subanalyses revealed a preferential association of hsp65 antibody titers with advanced lesions (odds ratio, 1.42; 95% CI, 1.02 to 1.98; Pϭ0.039). Other risk factors neither confounded nor modified this association. Finally, hsp65 antibody titers significantly predicted the 5-year mortality (hazard ratio, 1.52; 95% CI, 1.14 to 2.03; PϽ0.001). Conclusions-These findings indicate a sustained existence of anti-hsp65 antibodies in subjects with severe atherosclerosis, which is predictive for mortality. (Circulation. 1999;100:1169-1174.)

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“…Heat-shock proteins show considerable sequence homology among species, and immune reactions to Hsp60 in infections by microorganisms that express Hsp65 have been widely described (3). Anti-Hsp65 antibodies, induced in response to these pathogens, can cross-react with self Hsp60 expressed on endothelial cells (4)(5)(6)(7). Elevated levels of anti-Hsp60 have been associated with progression and severity of atherosclerosis (8)(9)(10)(11)(12)(13)(14)(15), with vasculitis in systemic autoimmune diseases (16), and with thrombotic events in the context of systemic lupus erythematosus (SLE) and lupus anticoagulant (LAC) positivity (17).…”

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confidence: 99%

Association of autoantibodies to heat‐shock protein 60 with arterial vascular events in patients with antiphospholipid antibodies

Dieudé¹,

Correa²,

Neville³

et al. 2011

Arthritis & Rheumatism

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Objective. Anti-heat shock protein 60 autoantibodies (anti-Hsp60) are associated with cardiovascular disease and are known to affect endothelial cells in vitro, and we have recently shown that anti-Hsp60 promote thrombosis in a murine model of arterial injury. Based on those findings, we undertook the present study to investigate the hypothesis that the presence of antiHsp60, alone or in combination with other thrombogenic risk factors, is associated with an elevated risk of vascular events.Methods. The study population was derived from 3 ongoing cohort studies: 2 independent systemic lupus erythematosus (SLE) registries and 1 cohort comprising SLE patients and non-SLE patients. Data from a total of 402 participants were captured; 199 of these participants had had confirmed vascular events (arterial vascular events in 102, venous vascular events in 76, and both arterial and venous vascular events in 21). Anti-Hsp60 were detected by enzyme-linked immunoassay, and association with vascular events was assessed by regression analysis. Conclusion. We demonstrate that anti-Hsp60 are associated with an increased risk of arterial vascular events, but not venous vascular events, in aPL-positive individuals. These data suggest that anti-Hsp60 may serve as a useful biomarker to distinguish risk of arterial and venous vascular events in patients with aPL. Results. Multiple regression analysis revealed

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Protein kinase A-catalyzed phosphorylation of heat shock protein 60 chaperone regulates its attachment to histone 2B in the T lymphocyte plasma membrane

Cited by 107 publications

References 54 publications

Pepsin-Mediated Processing of the Cytoplasmic Histone H2A to Strong Antimicrobial Peptide Buforin I

Pepsin-Mediated Processing of the Cytoplasmic Histone H2A to Strong Antimicrobial Peptide Buforin I

Association of Serum Antibodies to Heat-Shock Protein 65 With Carotid Atherosclerosis

Association of autoantibodies to heat‐shock protein 60 with arterial vascular events in patients with antiphospholipid antibodies

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