Glucocorticoid evoked upregulation of RCAN1-1 in human leukemic CEM cells susceptible to apoptosis

Abstract

Background: Glucocorticoid hormones (GCs) induce apoptosis of leukemic T-cells by transcriptional regulation via the GC receptor, GR. In the human leukemic CEM cell culture model, RCAN1 has been identified as one of the genes that is specifically upregulated only in the GCsensitive CEM C7-14 cells, but not in the GC-resistant CEM-C1-15 sister cells in correlation with GC-evoked apoptosis. RCAN1 gene encodes two major protein isoforms of the regulator of calcineurin (RCAN1), RCAN1-1 and RCAN1-4 via alternative splicing of exons 1 and 4 respectively, to exons 5-7. Studies reported here evaluated the differential regulation and function of the two transcripts and protein products of RCAN1 by the synthetic GC dexamethasone (Dex), and by modulators of calcium signaling.

Chronic high levels of the RCAN1-1 protein may promote neurodegeneration and Alzheimer disease

“…RCAN1-1L levels can be specifically increased by glucocorticoids [29,30], whose production is known to be stimulated by multiple stresses. High glucocorticoid levels can lead to neurodegeneration, and we hypothesize that stress-induced production of glucocorticoids may actually cause neurodegeneration by elevating RCAN1-1L.…”

Comparison of Direct Action of Thiazolidinediones and Glucocorticoids on Renal Podocytes: Protection from Injury and Molecular Effects

“…CaN inhibitors, including tacrolimus (FK506) and cyclosporine, are widely used drugs for the treatment of NS in cases in which GCs are clinically ineffective. Previous reports have demonstrated the ability of Dex to stimulate CaN phosphatase activity in some cell types and suppress it in other cell types (Tumlin et al, 1997;Hirakawa et al, 2009). To date, the ability of neither Rosi, Pio, nor even Dex to alter CaN activity in podocytes has been studied.…”

Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) Targets Down Syndrome Candidate Region 1 (DSCR1/RCAN1) to control Neuronal Differentiation

“…After ischemic insult, up-regulation of RCAN1.4 in the peri-infarct cortex has also been reported (7). RCAN1.1, a 36-to 41-kDa protein, is up-regulated by glucocorticoid and dexamethasone in human leukemic cells via the glucocorticoid response element (8,9). Chronic RCAN1 overexpression is associated with DS and Alzheimer disease, and RCAN1 deficiency has been reported in Huntington disease (2,4,10,11).…”