Activation of calcineurin-dependent nuclear factor of activated T cells c1 (NFATc1) is convergent for normal bone homeostasis. NFATc1 regulates both osteoclastogenesis and osteoblastogenesis. Here we investigated the roles of regulator of calcineurin (RCAN) genes in bone homeostasis. RCANs function as potent physiological inhibitors of calcineurin. Overexpression of RCANs in osteoclast precurso...

background: calcineurin inhibitors (cni) have significantly reduced the incidence of acute rejection. nephrotoxicity however may contribute to long-term allograft dysfunction. mycophenolate mofetil (mmf) may allow cyclosporine (csa) dose reduction without increasing the risk of rejection. methods: in seventy-eight living unrelated kidney transplant patients with renal dysfunction, we studied th...

Multiple intracellular signaling pathways have been shown to regulate the hypertrophic growth of cardiomyocytes. Both necessary and sufficient roles have been described for the mitogen activated protein kinase(1) (MAPK) signaling pathway, specific protein kinase C (PKC) isoforms, and calcineurin. Here we investigate the interdependence between calcineurin, MAPK, and PKC isoforms in regulating c...

We have compared the pharmacodynamic properties of calcineurin inhibitors tacrolimus and cyclosporin A in rats to clarify the different therapeutic drug monitoring strategy of both drugs in a clinical situation. In various tissue extracts, the inhibition of calcineurin activity by cyclosporin A was significantly greater than that by tacrolimus at the same drug concentration (1 microM) in the th...

The longer survival of liver transplant recipients has emphasized the need to consider complications that develop several years after liver transplantation, such as chronic renal dysfunction. Renal dysfunction has an impact on long-term posttransplant morbidity and mortality. The prevalence of chronic renal disease among liver transplant recipients varies widely from 10 to 78%. This renal dysfu...

In Candida albicans, calcineurin mediates tolerance to azole antifungal drugs, survival in serum, and virulence. In this study, we examined 24 Candida isolates from liver transplant recipients receiving a calcineurin inhibitor as a component of their immunosuppressive therapy. We were unable to detect a difference in susceptibility to calcineurin inhibitors in combination with fluconazole, seru...

Gooch, Jennifer L. An emerging role for calcineurin A in the development and function of the kidney. Am J Physiol Renal Physiol 290: F769–F776, 2006; doi:10.1152/ajprenal.00281.2005.—For many years, calcineurin has been a familiar molecule as a target of the immunosuppressive agents cyclosporin A and FK-506. Calcineurin inhibition interferes with T cell signaling by preventing activation of the...

Acoustic overstimulation increases Ca(2+) concentration in auditory hair cells. Because calcineurin is known to activate cell death pathways and is controlled by Ca(2+) and calmodulin, this study assessed the role of calcineurin in auditory hair cell death in guinea pigs after intense noise exposure. Immediately after noise exposure (4-kHz octave band, 120 dB, for 5 hr), a population of hair ce...

Topical calcineurin inhibitors (TCI) are a relatively new class of drugs used in dermatology. There are two drug forms available - tacrolimus 0.03% or 0.1% ointment and 1.0% pimecrolimus cream. The drugs act by inhibiting synthesis of proinflammatory cytokines. The only approved indication for using TCI is treatment of atopic dermatitis. The TCI may be used as an alternative therapy to corticos...