Abstract 1424: Mipu1 encodes a Novel Ischemic Preconditioning Up-regulated Zinc Finger Protein and Protects Cardiac Myocytes from Apoptosis
Background: A novel myocardial ischemic preconditioning (IPC) up-regulated gene, Mipu1, was recently discovered in rat heart. This study was designed to further characterize the functional role of Mipu1 in cardioprotection.
Methods and Results: RT-PCR, sequencing and multiple-tissue Northern blots were used to determine the open reading frame (ORF) and tissue distribution of Mipu1. The full-length cDNA of Mipu1 had an ORF of 1827 base pairs (bp) which encodes 608 amino acids. Bioinformatical analysis revealed a KRAB domain and a LIM domain at the N-terminus and 14 successive Cys(2)His(2) (C2H2) type zinc finger domains at the C-terminus of the protein. There was a bipartite nuclear targeting sequence from amino acid 193 to 277. Mipu1 is expressed abundantly in heart and brain and seldom in other tissues. When the GFP-tagged Mipu1 was transiently expressed in C2C12 myogenic cells Mipu1 was identified in the nucleus. Overexpression of Mipu1 in C2C12 cells promoted the growth of these cells under serum deprivation and protected these cells against apoptosis and necrosis induced by H2O2.
Conclusion: Mipu1 may be a novel zinc finger protein and its up-regulation during IPC may protect the heart against ischemia/reperfusion injury. Therefore, further study of the function of Mipu1 in the heart may provide novel insights into understanding the molecular mechanisms for IPC and new therapeutic targets for treatment of ischemic heart diseases.