| 1. |
- Goncalves, Isabel, et al.
(författare)
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Activation of calpain-1 in human carotid artery atherosclerotic lesions
- 2009
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 9:26
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Tidskriftsartikel (refereegranskat)abstract
- Background: In a previous study, we observed that oxidized low-density lipoprotein-induced death of endothelial cells was calpain-1-dependent. The purpose of the present paper was to study the possible activation of calpain in human carotid plaques, and to compare calpain activity in the plaques from symptomatic patients with those obtained from patients without symptoms. Methods: Human atherosclerotic carotid plaques (n = 29, 12 associated with symptoms) were removed by endarterectomy. Calpain activity and apoptosis were detected by performing immunohistochemical analysis and TUNEL assay on human carotid plaque sections. An antibody specific for calpain-proteolyzed alpha-fodrin was used on western blots. Results: We found that calpain was activated in all the plaques and calpain activity colocalized with apoptotic cell death. Our observation of autoproteolytic cleavage of the 80 kDa subunit of calpain-1 provided further evidence for enzyme activity in the plaque samples. When calpain activity was quantified, we found that plaques from symptomatic patients displayed significantly lower calpain activity compared with asymptomatic plaques. Conclusion: These novel results suggest that calpain-1 is commonly active in carotid artery atherosclerotic plaques, and that calpain activity is colocalized with cell death and inversely associated with symptoms.
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| 2. |
- Reeve, Janice L. V., et al.
(författare)
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OxLDL-induced gene expression patterns in CASMC are mimicked in apoE(-/-) mice aortas
- 2007
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 356:3, s. 681-686
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Tidskriftsartikel (refereegranskat)abstract
- Oxidized low density lipoprotein (oxLDL) contributes to the pathophysiology of atherosclerosis, partly by altering gene expression in vascular cells. Here, we show 221 genes differentially regulated by oxLDL in coronary artery smooth muscle cells (CASMC), using oligonucleotide microarrays. These genes were classified into 14 functional groups. A comparable gene expression pattern was detected in apoE(-/-) mice. OxLDL induced an oxidative stress response in CASMC, but not the unfolded protein response. OxLDL also caused CASMC death which was accompanied by increased expression of FasL, Bax, and p53 but was caspase-independent. This approach provides further insight into disease pathology and prognosis. (c) 2007 Elsevier Inc. All rights reserved.
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| 3. |
- Stollenwerk, Maria M, 1959-, et al.
(författare)
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Very low-density lipoprotein induces interleukin-1beta expression in macrophages
- 2005
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier. - 0006-291X .- 1090-2104. ; 335:2, s. 603-608
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Tidskriftsartikel (refereegranskat)abstract
- Elevated plasma level of very low-density lipoprotein (VLDL) is a risk factor for coronary heart disease. We investigated the effect of VLDL on expression of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) in human peripheral blood monocyte-derived macrophages. IL-1beta mRNA and protein expression was analysed by PCR and ELISA, respectively. Caspase activation was assessed by immunoblotting. Apart from potentiating lipopolysaccharide-induced secretion of IL-1beta, VLDL alone induced secretion of IL-1beta from human monocyte-derived macrophages. This effect was suppressed by an inhibitor of caspase-1, the protease which cleaves pro-IL-1beta. VLDL treatment activated caspase-1, as indicated by increased levels of the caspase-1 p20 subunit. Furthermore, VLDL increased IL-1beta mRNA expression, which was associated with activation of transcription factor AP-1. Inhibition of caspase-1 did not influence IL-1beta mRNA expression. In conclusion, VLDL induces IL-1beta mRNA expression, caspase-1 activation, and IL-1beta release from macrophages, suggesting that VLDL can promote inflammation in atherosclerotic lesions.
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| 4. |
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| 5. |
- Grethe, Simone, et al.
(författare)
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p38 MAPK regulates phosphorylation of Bad via PP2A-dependent suppression of the MEK1/2-ERK1/2 survival pathway in TNF-alpha induced endothelial apoptosis.
- 2006
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Ingår i: Cellular Signalling. - : Elsevier BV. - 1873-3913 .- 0898-6568. ; 18:4, s. 531-540
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Tidskriftsartikel (refereegranskat)abstract
- We recently reported that p38 MAPK regulates TNF-induced endothelial apoptosis via phosphorylation and downregulation of Bcl-xL. Here, we describe that such apoptosis includes p38 NIAPK-mediated, protein phosphatase 2A (PP2A)-dependent, downregulation of the MEK-ERK pathway. Inhibition of PP2A with fostriecin or calyculin A significantly increased MEK phosphorylation, as did exposure to the p38 MAPK inhibitor SB203580. Inhibition of MEK potentiated TNF-induced caspase-3 activity and cell death, and both those events were suppressed by treatment with fostriecin or calyculin A. Immunoprecipitation experiments revealed an association between p38 MAPK, PP2A and MEK, and the results of a phosphatase assay suggested that PP2A is a downstream target of p38 MAPK. Importantly, phosphorylation of Bad at Ser-112 was found to be regulated by p38 MAPK and PP2A. In summary, the present findings indicate a novel p38 MAPK-mediated apoptosis pathway, involving activation of Bad via PP2A-dependent inhibition of the MEK-ERK pathway. (c) 2005 Elsevier Inc. All rights reserved.
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