Endoplasmic reticulum (ER) stress can trigger apoptosis and necrosis in many types of mammalian cells. Previous studies in yeast found little or no cell death in response to the ER stressor tunicamycin, but a recent study suggested widespread apoptosis-like death. Here we show that wild-type laboratory Saccharomyces cerevisiae cells responding to tunicamycin die by nonapoptotic mechanisms in lo...

Calcineurin is protein phosphatase with characteristic calciumand calmodulin-dependent activation through its regulatory subunits. Activated calcineurin dephosphorylates downstream transcription factor nuclear factor of activated T cells (NFAT), which leads to its nuclear translocation and transcriptional activation. Calcineurin-NFAT signaling axis is initially discovered as an essential pathwa...

Since the pioneering experiments of Peter Medawar in the 1950s, immunosuppressive drugs have been used to inhibit the immune rejection of organ transplants in man (Medawar, 1958). Although early approaches were based upon cortisone and azathioprine, the discovery of the calcineurin inhibitor cyclosporin A in the 1970s was a major breakthrough that enabled transplantation to become an establishe...

ABSTRACT A 13-year-old boy known for steroid-resistant nephrotic syndrome taking cyclosporine the last four years was referred from one private hospital non-response to treatment and decreased hearing. On detailed history, it revealed that hearing loss started after initiation of with during first year, patient not properly followed issues. Rather continued despite no response treatment. The ra...

Pesticides can significantly harm reproduction in animals and people. Pyrethroids are often used as insecticides, and their toxicity for mammals is considered to be low. However, cypermethrin, deltamethrin and fenvalerate - as potent specific inhibitors of protein phosphatase calcineurin - can influence the meiosis of mammalian oocytes. The objective of this study was to evaluate the effects of...

The immunosuppressive agents cyclosporin A (CsA) and FK-506 have previously been shown to exhibit neurotrophic and neuroprotective properties in vivo. Given that significant clinical expertise exists for both drugs, they represent an attractive starting point for treatment of acute neural injuries. One putative mechanism for neuroprotection by these drugs relates to inhibition of calcineurin ac...