RGD Reference Report - INHIBITION OF p53 BY PIFITHRIN-alpha REDUCES MYOCYTE APOPTOSIS AND LEUKOCYTE TRANSMIGRATION IN AGED RAT HEARTS FOLLOWING 24 HOURS OF REPERFUSION. - Rat Genome Database

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INHIBITION OF p53 BY PIFITHRIN-alpha REDUCES MYOCYTE APOPTOSIS AND LEUKOCYTE TRANSMIGRATION IN AGED RAT HEARTS FOLLOWING 24 HOURS OF REPERFUSION.

Authors: Liu, P  Xu, B  Cavalieri, TA  Hock, CE 
Citation: Liu P, etal., Shock. 2008 Feb 28;.
RGD ID: 2290554
Pubmed: (View Article at PubMed) PMID:18317410
DOI: Full-text: DOI:10.1097/SHK.0b013e31816a192d

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 ratswere 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.

Annotation

Disease Annotations    

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Tp53  (tumor protein p53)

Genes (Mus musculus)
Trp53  (transformation related protein 53)

Genes (Homo sapiens)
TP53  (tumor protein p53)


Additional Information