Expression of Egr1 and p53 in human carotid plaques and apoptosis induced by 7-oxysterol or p53

• Published in: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie Vol. 65; no. 5; pp. 677 - 682
• Main Authors: Miah, Sayem, Zadeh, Shahram Nour Mohammad, Yuan, Xi-Ming, Li, Wei
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.07.2013
• Subjects: 7-Oxysterols; Animals; Apoptosis; Apoptosis - drug effects; Atherosclerosis; Carotid Stenosis - chemically induced; Carotid Stenosis - metabolism; Carotid Stenosis - pathology; Cell Culture Techniques; Early Growth Response Protein 1 - biosynthesis; Early Growth Response Protein 1 - genetics; gene expression regulation; Humans; Hydroxycholesterols - toxicity; Immediate-early response protein (Egr-1); Immunohistochemistry; Ketocholesterols - toxicity; MEDICIN; MEDICINE; Mice; Nuclear fragmentation; p53; reactive oxygen species; Reactive Oxygen Species - metabolism; Tumor Suppressor Protein p53 - biosynthesis; Tumor Suppressor Protein p53 - genetics; U937 Cells; 7-Oxysterols; Immediate-early response protein (Egr-1); Atherosclerosis; Apoptosis; p53; Nuclear fragmentation
• ISSN: 0940-2993; 1618-1433; 1618-1433
• DOI: 10.1016/j.etp.2012.08.002

Egr-1 and p53 are involved in pathology of both atherosclerosis and cancer. However, it is unknown whether p53 and Egr1 are interactively involved in apoptosis in atherosclerosis. We found that in human carotid plaques, the expression of p53 was inversely correlated with Egr1. In U937 cells, 7β-hydroxycholesterol and 7-ketocholesterol induced production of reactive oxygen species (ROS), transient up-regulation of Egr1 followed by late induction of p53 and apoptosis. Cells with nuclear fragmentation induced by 7-oxysterol or p53 showed increased levels of p53, but decreased levels of Egr1. In conclusion, ROS induced by 7-oxysterols may function as an early initiator of Egr1 expression. The late induced p53 by 7-oxysterols contributes to apoptotic cell death and is linked to the reduction of Egr1 levels, which resembles the differential expression of p53 and Egr1 in human atheroma progression.