Nucleolin involved in myocardial ischaemic preconditioning via post-transcriptional control of HSPA1A expression.

AIMS:Recent studies have identified the critical roles of nucleolin in a variety of cellular processes, including regulation of viral replication and tumour formation. However, the possible roles of nucleolin in myocardial preconditioning remain undefined. METHODS AND RESULTS:We used an in vivo rat myocardial ischaemic preconditioning (IP) model (four cycles of 5 min ischaemia and 10 min reperfusion) and cellular hydrogen peroxide preconditioning (H2O2-PC) models. We found that nucleolin mRNA and protein expression showed a time-dependent increase during the recovery of myocardial ischaemic preconditioning in rats and H2O2-PC in neonatal rat cardiomyocytes. Nucleolin overexpression enhanced the protective effects of H2O2-PC, whereas nucleolin ablation abrogated the H2O2-PC-mediated protection in cardiomyocytes. On the other hand, nucleolin overexpression increased the stabilization of the mRNA and the expression of Hduanyu18421A protein in cardiomyocytes, whereas nucleolin ablation abrogated the up-regulation of Hduanyu18421A induced by H2O2-PC in cardiomyocytes. An interaction between nucleolin and Hduanyu18421A mRNA was further identified using the RNA-protein interaction studies. Reporter gene assays, which depended on the untranslated regions (UTR) of Hduanyu18421A mRNA, revealed that the post-transcriptional regulation was mainly attributed to the Finally, Hduanyu18421A anti-sense oligonucleotides (asODNs) attenuated the protective effect of nucleolin in cardiomyocytes. CONCLUSION:These results indicate that nucleolin is up-regulated and involved in myocardial protection of ischaemic preconditioning via a post-transcriptional control of Hduanyu18421A expression.

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