Disease relevance of Cabin1

• Both a calcineurin inhibitor, FK506, and a selective NMDA receptor antagonist, MK-801, inhibit the dephosphorylation of DAPK after in vitro ischemia [1].
• RESULTS: Administration of angiotensin II type 1 receptor antagonist and calcineurin inhibitor did not affect blood pressure and allowed the development of compensatory hypertrophy [2].
• The gene for Down Syndrome Critical Region-1 (DSCR1) encodes a protein that is an endogenous calcineurin inhibitor [3].
• Among these genes, we focused on glycogen synthase kinase (GSK)-3beta, calcineurin-inhibitor (Cain), and endothelin (ET)-1 for their implicated roles in pathological cardiac hypertrophy, and confirmed the results of microarray analysis at mRNA and protein/peptide levels using quantitative PCR, Western blot, and EIA analyses [4].
• Treatment of rats with a calcineurin inhibitor, FK506, inhibited the activation of calcineurin and prevented the pressure overload-induced cardiac hypertrophy and fibrosis without change of hemodynamic parameters [5].

High impact information on Cabin1

• The effect in nerve terminals was prevented by the calcineurin inhibitor cyclosporin A [6].
• This heterosynaptic reversal occurred without modification of naive responses, and it was prevented by D-AP5, an NMDA receptor antagonist, or cyclosporin A, a calcineurin inhibitor [7].
• Taken together, these results indicate that calpain cleaves the calcineurin-binding domain of cain/cabin1 to activate Cn and elicit calcium-triggered cell death [8].
• Here, we report that the up-regulation of slow myosin heavy chain (MyHC) and a MyHC-slow promoter induced by slow motor neurons in regenerating rat soleus muscle is prevented by the calcineurin inhibitors cyclosporin A (CsA), FK506, and the calcineurin inhibitory protein domain from cain/cabin-1 [9].
• Immunosuppressive drugs used were tacrolimus (a calcineurin inhibitor) and its synergistic partners, rapamycin (a regulator of the mammalian target of rapamycin [mTOR]) and mycophenolate mofetil (an inosine monophosphate dehydrogenase inhibitor) [10].

Chemical compound and disease context of Cabin1

• IGF-1-mediated ARVM hypertrophy was also attenuated by cyclosporine A (calcineurin inhibitor), and staurosporine and chelerythrine (protein kinase C inhibitors) [11].

Biological context of Cabin1

• Calpain-dependent cleavage of cain/cabin1 activates calcineurin to mediate calcium-triggered cell death [8].
• Mouse cain/cabin1 was identified from a thymus cDNA library by an in vitro substrate-screening assay with calpain [8].
• Like calcineurin, cain has a prominent neuronal expression and a wide tissue distribution [12].
• Calcineurin is also involved in the maintenance of the slow muscle fiber gene program because in the adult soleus muscle, cain causes a switch from MyHC-slow to fast-type MyHC-2X and MyHC-2B gene expression, and the activity of the MyHC-slow promoter is inhibited by CsA and FK506 [9].
• Differential effects of a calcineurin inhibitor on glutamate-induced phosphorylation of Ca2+/calmodulin-dependent protein kinases in cultured rat hippocampal neurons [13].

Anatomical context of Cabin1

• These data demonstrate that biomechanical strain directly induces gene expression for the calcineurin inhibitor DSCR1 in cardiac myocytes, indicating that mechanically induced DSCR1 may regulate the hypertrophic response to mechanical overload [3].
• Tacrolimus is a calcineurin inhibitor that passes the blood-brain barrier and may increase cerebrovascular tone and restrict cerebral ammonia influx [14].
• FK506, a calcineurin inhibitor unrelated to CsA, inhibits proliferation of astrocytes and induces death accompanied by apoptotic changes in nuclear morphology and DNA fragmentation [15].
• The possibility that the difference in the control of GFAP phosphorylation in the two structures is related to differences in the control of GFAP dephosphorylation was investigated by incubating spinal cord slices with the calcineurin inhibitor FK506 in the presence of Ca2+ [16].
• Cyclosporin A, a calcineurin inhibitor, was administered into the rat hippocampus [17].

Associations of Cabin1 with chemical compounds

• The effects of Ca(2+) and Pb(2+) were additive and blocked completely by the mitochondrial permeability transition pore (PTP) inhibitor cyclosporin A, whereas the calcineurin inhibitor FK506 had no effect [18].
• The dephosphorylation of IRS-1 by NMDA was calcium-dependent and was inhibited by the calcineurin inhibitor cyclosporine [19].
• Deltamethrin (20 nM), another calcineurin inhibitor, had a similar protective effect, whereas okadaic acid did not [20].
• BACKGROUND: FTY720 is a novel immunomodulator that may provide an opportunity for a reduction in calcineurin inhibitor dosage in transplant recipients with renal/hepatic side effects [21].
• Combination of these stimuli with ionomycin resulted in a strongly synergistic increase of CD134 expression, which was blocked by the calcineurin-inhibitor cyclosporin A [22].

Regulatory relationships of Cabin1

• The immunosuppressant calcineurin inhibitor FK506 inhibited the down-regulation of the PMCA4CII at both the protein and the mRNA level but did not affect the changes of the other PMCA pumps [23].
• IGF-I treatment stimulated calcineurin activity and increased the protein levels of calcineurin and the calcineurin binding protein, calmodulin [24].

Other interactions of Cabin1

• By using either the CaM kinase II inhibitor KN-62, the calcineurin inhibitor FK 506 or the protein kinase A (PKA) inhibitor Rp-8-Br-cAMPS, the GIP-mediated Galphai2 mRNA increase was fully reversed [25].
• Increased cytosolic Ca2+ and calcineurin activation stimulated Bad translocation since BAPTA [bis-(o-aminophenoxy)ethane-N, N, N', N'-tetra-acetic acid], an intracellular Ca2+ chelator, and cyclosporin A, a calcineurin inhibitor, significantly reduced translocation [26].
• FK506, a specific calcineurin inhibitor, inhibited the enhancing effect of adenosine on the NGF-induced neurite outgrowth and increased the duration of p38 MAP kinase phosphorylation without affecting ERK phosphorylation [27].
• The inhibitory effect of Ca2+/CaM was attenuated by the CaM antagonists W-7, prenylamine and CaM-kinase II fragment (290-309), but not by the calcineurin inhibitor FK506 [28].
• Cardioprotective effects of the calcineurin inhibitor FK506 and the PAF receptor antagonist and free radical scavenger, EGb 761, in isolated ischemic/reperfused rat hearts [29].

Analytical, diagnostic and therapeutic context of Cabin1

• We now report the identification, molecular cloning, and functional characterization of a novel protein, cain (calcineurin inhibitor), that interacts with and inhibits calcineurin [12].
• CONCLUSIONS: Changing from CsA to a combined therapy of MMF with S1P agonist is a promising strategy in clinical transplantation to overcome CI-induced nephrotoxicity and chronic rejection [30].
• A calcineurin inhibitor blocked the increase in both TUNEL and nitrotyrosine positivity [31].
• Co-administration of the calcineurin inhibitor cyclosporine and the mTOR inhibitors sirolimus or everolimus increases the efficacy of immunosuppression after organ transplantation [32].
• Ca2 + reperfusion injury induced by Ca2 + depletion or H2O2 exposure was blocked by the iron chelator 1, 10-phenanthroline, the NF-kappaB inhibitor pyrrolidinedithiocarbamate and the calcineurin inhibitor FK506 [33].

References