The Distribution Of Calcineurin In Heart Tissue

Calcineurin is a unique Ca²⁺/calmodulin-dependent serine/threonine phosphatase(phosohatase 2B) and is composed of a heterodimer containing a catalytic subunit,calcineurin A,which has a calmodulin-binding site and a regulatory subunit, calcineurin B,which can increase the activity of calcineurin by combining with Ca²⁺.The primary sequence of both subunits and heterodimeric quaternary structure is highly conserved from yeast to mammals. CnAα CnAβ CnAγ are three isoforms of calcineurin in hunman body. Of which,CnAγ is only found in didymu.CnAα and CnAβ exist in various organs and tissues. CnAα-isoform mainly participate in many signal transductions. Activated calcineurin dephosphorylates a family of transcription factor knowns as NFAT,which translocated from cytoplasm to nucleus. NFAT can involved in the modulation of transcription activity and expression of various genes through interacting with many transcription factors. Calcineurin is potently inhibited by immunosuppressant drugs,cyclosporin A and FK506,in the presence of their respective cytoplasmic immunophilin proteins,cyclophilin and FK506-binding protein.Calcineurin is a widespread and multifunctional protein phosphatase,and can involve in modulating the functions of diverse cells. It was first purified from bovine cardiac muscle by Wolf H. Furthermore, both subunits of calcineurin can be identified in crude homogenates of bovine cardiac muscle by using rabbit polyclonal antibodies to bovine brain calcineurin. We've known that activated calcineurin can participate in a number of signal pathway associated with hypertrophy. Recogination the distribution of calcineurin may help people make further understanding the importance of calcineurin in cardiocascular diseases.Objective:To discuss the distribution of calcineurin in heart tissue.Methods: We study the left ventricular papillary muscles from 5 patients with mitral lesion who would undergo valvular replacement operation from Dec 2006 to Feb 2007 in Shandong provincial hospital. All patients didn't take calcineurin inhibitor ( CsA and FK-506) (1)To observe the distribution of various cells in heart tissue through haematoxylin and eosin stain.(2)We adopt immunohistochemistry technique to observe the distribution of calcineurin in heart tissue,and found the best staining effect by changing different antibody concentration to deal with samples.Results:Samples with 1:100 antibody concentration had the best staining effect after AEC staining. No matter patients with mitral lesion or not,we can find cardinal red particals in cardiac muscle cells fibroblasts mesothelial cells. In vascular smooth muscle cells ,there was no positive particals to be found. Instead of first antibody with buffer solution,there was no difference between trial groups and control groups.Conclusions: As a kind of widespread and multifunctional protein phosphatase,calcineurin can be found to express in cardiac muscle cells fibroblasts, mesothelial cells,but was not found in vascular smooth muscle cells. It may directly or indirectly implicate its important role in cardiac hypertrophy,but it's function in mesothelial cells still keep unknown. Our findings also significantly conduce to study the relationship between calcineurin and cardiovascular-related diseases.