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BETA
Osman, Ehab
Publications (3 of 3) Show all publications
Li, W., Laskar, A., Sultana, N., Osman, E., Ghosh, M., Li, Q. & Yuan, X. (2012). Cell death induced by 7-oxysterols via lysosomal and mitochondrial pathways is p53-dependent. Free Radical Biology & Medicine, 53(11), 2054-2061
Open this publication in new window or tab >>Cell death induced by 7-oxysterols via lysosomal and mitochondrial pathways is p53-dependent
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2012 (English)In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 53, no 11, p. 2054-2061Article in journal (Refereed) Published
Abstract [en]

Oxysterol accumulation and p53 expression mainly in macrophages have been associated with cell death and necrotic core formation in human atheroma progression. Oxidative stress and lysosomal membrane permeabilization (LMP) in macrophages are important causes of macrophage apoptosis. However, it is not understood how p53 and oxysterols interact in the process. We show here that 7-oxysterols induce endogenous full-length p53 and phospho-p53 (p53-Ser15) in both nucleus and cytoplasm of THP1 and J774 cells, which is followed by cellular oxidative stress and apoptotic cell death. The role of p53 in 7-oxysterol-mediated cell death is further investigated in temperature sensitive p53-transfected (M1-t-p53) and in p53-deficient (M1) cells. These results reveal that 7-oxysterols induce induction and nuclear translocation of p53 in M1-t-p53 cells, which in turn enhances LMP, mitochondrial translocation of Bax, mitochondrial membrane permeabilization, cytosolic release of cytochrome c, and cell death. Most importantly, the above effects of 7-oxysterols were not observed in p53-deficient M1 cells. The findings reveal that 7-oxysterol-induced cell death occurs via p53-dependent pathways. Subsequent p53 nuclear translocation and induction of wild-type and phosphorylated p53 are early steps in oxysterol-induced lysosomal-mitochondrial pathways involved in cell death.

Place, publisher, year, edition, pages
Elsevier, 2012
Keywords
Apoptosis, Atherosclerosis, Bax, Lysosomes, Mitochondria, Oxidative stress, Free radicals
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-86892 (URN)10.1016/j.freeradbiomed.2012.09.007 (DOI)000312058300007 ()
Note

Funding Agencies|Swedish Heart Lung Foundation||Torsten and Ragnar Soderbergs Foundation||Stroke Foundation||Olle Engkvist Foundation||Swedish Gamla Tjanarinnor Foundation||Linkoping University||Linkoping University Hospital||

Available from: 2013-01-07 Created: 2013-01-07 Last updated: 2017-12-06
Yuan, X.-M., Osman, E., Miah, S., Zadeh, S. N., Xu, L., Forssell, C. & Li, W. (2010). p53 expression in human carotid atheroma is significantly related to plaque instability and clinical manifestations. Atherosclerosis, 210(2), 392-399
Open this publication in new window or tab >>p53 expression in human carotid atheroma is significantly related to plaque instability and clinical manifestations
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2010 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 210, no 2, p. 392-399Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The expression of p53 has been associated with DNA damage, cell senescence, proliferation and apoptosis in human atherosclerotic plaques. However, it is largely unknown whether p53 expression is related to the stability and clinical manifestations of atherosclerotic plaques in humans. In the present study, we examined whether p53 expression is related to clinical symptoms and plaque integrity in patients with carotid atherosclerosis (n=62). We also investigated p53 expression and its relation to apoptosis and apoptosis-related cathepsin L and ferritin in the carotid lesions. METHODS AND RESULTS: We found that smooth muscle cells often had nuclear p53 in the shoulder region of carotid lesions while CD68-positive macrophages, which had both nuclear and cytoplasmic p53, frequently appeared in the surrounding areas of necrotic cores or plaque cap regions. Quantitative image analysis of immunohistochemistry showed that p53 expression was significantly increased in plaques with necrotic core formation or cap rupture and lesions from patients with transient ischemic attacks (TIAs). The levels of p53 expression was significantly increased in more severe stenosed lesions but decreased with prolonged time between symptom onset and carotid endarterectomy. Furthermore, p53 expression was significantly correlated with the expression of ferritin, lysosomal cathepsin L, and apoptosis. CONCLUSION: The increased p53 expression, particularly macrophage p53 levels, is associated with the enlargement of necrotic cores, plaque rupture and clinical manifestations of carotid plaques. Concomitant increases of lysosomal cathepsin, ferritin, and p53 levels may promote the apoptosis and atheroma progression in patients with carotid atherosclerosis.

Keywords
Atherosclerosis, Cathepsin, Cell death, Ferritin, Iron, Lysosomes
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-56719 (URN)10.1016/j.atherosclerosis.2009.11.048 (DOI)000278036800013 ()20060114 (PubMedID)
Available from: 2010-06-01 Created: 2010-06-01 Last updated: 2018-01-12
Li, W., Osman, E., Forssell, C. & Yuan, X. (2009). THROMBIN RECEPTOR (PAR1), TISSUE FACTOR AND IRON BINDING PROTEINS IN HUMAN CAROTID ATHEROSCLEROSIS. In: ATHEROSCLEROSIS SUPPLEMENTS. Paper presented at The XV International Symposium on Atherosclerosis,June 14-18, 2009, Boston, MA USA (pp. e595-e595). Elsevier, 10(2)
Open this publication in new window or tab >>THROMBIN RECEPTOR (PAR1), TISSUE FACTOR AND IRON BINDING PROTEINS IN HUMAN CAROTID ATHEROSCLEROSIS
2009 (English)In: ATHEROSCLEROSIS SUPPLEMENTS, Elsevier, 2009, Vol. 10, no 2, p. e595-e595Conference paper, Poster (with or without abstract) (Other academic)
Place, publisher, year, edition, pages
Elsevier, 2009
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-66318 (URN)10.1016/S1567-5688(09)70582-3 (DOI)000207957101259 ()
Conference
The XV International Symposium on Atherosclerosis,June 14-18, 2009, Boston, MA USA
Available from: 2011-03-11 Created: 2011-03-11 Last updated: 2012-05-31
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