INHIBITION OF p53 BY PIFITHRIN-α REDUCES MYOCYTE APOPTOSIS AND LEUKOCYTE TRANSMIGRATION IN AGED RAT HEARTS FOLLOWING 24 HOURS OF REPERFUSION
| Autor: | Peitan Liu, Carl E. Hock, Baohuan Xu, Thomas A. Cavalieri |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Cardiac function curve Cardiac output medicine.medical_treatment Ischemia Apoptosis Enzyme-Linked Immunosorbent Assay Myocardial Reperfusion Injury Inflammation Pharmacology Critical Care and Intensive Care Medicine chemistry.chemical_compound Cell Movement Leukocytes medicine Animals Myocyte Benzothiazoles Saline Muscle Cells Pifithrin medicine.disease Immunohistochemistry Rats chemistry Immunology Emergency Medicine Tumor Suppressor Protein p53 medicine.symptom Toluene |
| Zdroj: | Shock. 30:545-551 |
| ISSN: | 1073-2322 |
| DOI: | 10.1097/shk.0b013e31816a192d |
| Popis: | Ischemic heart disease is a common age-related disease. Apoptotic cell death and inflammation are the major contributors to I/R injury. The mechanisms that trigger myocyte apoptosis and inflammation during myocardial I/R (MI/R) remain to be elucidated. Published data from our laboratory demonstrated that pretreatment of MI/R rats with pifithrin-alpha (PFT), a specific p53 inhibitor, reduced myocyte apoptosis and improved cardiac function compared with MI/R rats pretreated with saline at 4 h of reperfusion. In the present study, we investigated the effects of PFT on the occurrence of myocyte apoptosis and leukocyte transmigration in the later period of reperfusion. Aged (20-month-old) male F344 rats were subjected to 30 min of myocardial ischemia via ligature of the LCA, followed by 24 h of reperfusion. Pifithrin-alpha (2.2 mg/kg, intraperitoneally) or saline was administered to rats before ischemia. The results indicate that pretreatment of MI/R rats with PFT significantly decreased the percentage of infarct area to ischemic area (33 +/- 8 vs. 54 +/- 9, P < 0.05) and improved cardiac output (79 +/- 11 vs. 38 +/- 9 mL/min per 100 g body weight, P < 0.05) when compared with rats pretreated with saline at 24 h of reperfusion. The protective effects of PFT may involve the p53/Bax-mediated apoptosis because treatment of MI/R rats with PFT attenuated the ratio of Bax to Bcl2 (0.97 +/- 0.1 vs. 2.1 +/- 0.2, P < 0.05) and reduced myocyte apoptosis. Interestingly, inhibition of p53 transcriptional function by PFT alleviated leukocyte infiltration into the ischemic area of the heart (339 +/- 37 vs. 498 +/- 75 cells/10 high-power fields, P < 0.05). These data suggest that inhibition of p53 transcriptional function by PFT attenuates myocyte apoptosis and alleviates leukocyte transmigration at 24 h of reperfusion. The mechanisms by which p53 modulates leukocyte transmigration require further investigation. |
| Databáze: | OpenAIRE |
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