Journal
APOPTOSIS
Volume 27, Issue 3-4, Pages 246-260Publisher
SPRINGER
DOI: 10.1007/s10495-022-01714-3
Keywords
Sphingosylphosphorylcholine; Palmitate acid; EGR-1; Phosphorylation; JNK
Categories
Funding
- National Natural Science Foundation of China [31671180]
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Myocardial apoptosis induced by myocardial ischemia and hyperlipemia are the main causes of high mortality of cardiovascular diseases. This study found that early growth response protein 1 (EGR-1) is involved in both types of apoptosis and identified the mechanism of EGR-1 entering the nucleus.
Myocardial apoptosis induced by myocardial ischemia and hyperlipemia are the main causes of high mortality of cardiovascular diseases. It is not clear whether there is a common mechanism responsible for these two kinds of cardiomyocyte apoptosis. Previous studies demonstrated that early growth response protein 1 (EGR-1) has a pro-apoptotic effect on cardiomyocytes under various stress conditions. Here, we found that EGR-1 is also involved in cardiomyocyte apoptosis induced by both ischemia and high-fat, but how EGR-1 enters the nucleus and whether nuclear EGR-1 (nEGR-1) has a universal effect on cardiomyocyte apoptosis are still unknown. By analyzing the phosphorylation sites and nucleation information of EGR-1, we constructed different mutant plasmids to confirm that the nucleus location of EGR-1 requires Ser501 phosphorylation and regulated by JNK. Furthermore, the pro-apoptotic effect of nEGR-1 was further explored through genetic methods. The results showed that EGR-1 positively regulates the mRNA levels of apoptosis-related proteins (ATF2, CTCF, HAND2, ELK1), which may be the downstream targets of EGR-1 to promote the cardiomyocyte apoptosis. Our research announced the universal pro-apoptotic function of nEGR-1 and explored the mechanism of its nucleus location in cardiomyocytes, providing a new target for the homotherapy for heteropathy to cardiovascular diseases.
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