Disease relevance of Ppia

• Within areas of infarction, the basal IEG mRNA expression, and expression of the housekeeping gene cyclophilin A mRNA, decreased below control levels by 12 hours after the ischemia [1].
• These results taken together indicate that p31 represents one of the stress proteins whose expression is regulated primarily by thio-active compounds but not by hyperthermia [2].

High impact information on Ppia

• The mechanism of action of CyPA is likely to involve its prolyl isomerase activity because a mutant CyPA with a single amino acid substitution (arginine 55 to alanine) that is predicted to produce a 1000-fold attenuation in isomerase activity fails to reverse the cyclosporin A effect [3].
• This is because overexpression of CyPA and a CyPA mutant that is deficient in CsA binding activity reverses CsA-induced reduction in functional receptor expression [3].
• Sanglifehrin A (SfA), like CsA, exerts its immunosuppressive action by binding to cyclophilin A but at a different site from CsA, and unlike the latter, SfA does not inhibit calcineurin activity [4].
• Cyclophilin-A is involved in excitotoxin-induced caspase activation in rat neuronal B50 cells [5].
• Cyclophilin-A suppression largely reproduced the inhibitory effects of cyclosporin A [5].

Biological context of Ppia

• It is concluded that neuroprotection by cyclosporin A against excitotoxin-induced apoptosis is, at least partly, due to inhibition of cyclophilin-A [5].
• Cyclophilin-A suppression had no effect on cyanide-plus-2-deoxyglucose-induced cell death [6].
• Evidence that cyclophilin-A protects cells against oxidative stress [6].
• Amino acid sequence data showed that this protein was identical to cyclophilin A. Immunohistochemistry using antibodies against cyclophilin A found specific staining in pachytene spermatocytes, spermatids, interstitial cells, and Sertoli cell nuclei [7].
• Simvastatin (3 to 30 micromol/L) also dose-dependently inhibited LY83583-induced CyPA secretion likely via decreased isoprenylation of small GTPases [8].

Anatomical context of Ppia

• RESULTS: In untreated rats, membrane-bound CypA represents 0.25% of total brush border membrane (BBM) proteins, similar to the proportion found in the soluble fraction [9].
• CypA remained associated with the membranes following in vitro incubation of renal BBMs with CsA [9].
• In the present study, CypA was immunodetected and characterized following CsA treatment in subcellular fractions of renal cortex [9].
• The main target for CsA, cyclophilin A (CypA), was found in high levels in epithelial cells of renal proximal tubules [9].
• These data demonstrate that rat testis germ cells contain relatively high levels of cyclophilin A whose nuclease activity is associated with spermatocyte apoptosis induced by 2-methoxyethanol [7].

Associations of Ppia with chemical compounds

• However, cyclophilin-A-suppressed cells were markedly more sensitive to t-butylhydroperoxide [6].
• An 18-mer antisense phosphorothioate oligodeoxynucleotide was used to target a translated region of cyclophilin-A mRNA in rat neonatal cardiomyocytes [6].
• Association of cyclophilin A with renal brush border membranes: redistribution by cyclosporine A [9].
• High ionic strength treatment was unable to extract CypA from BBMs, whereas alkaline treatment (Na2CO2, pH 11) and detergent 3 - [(3 - cholamidopropyl) - dimethyl - ammonio] - 1 - propanesulfate (CHAPS) released it from BBMs [9].
• The data obtained from this study suggest that p31 induced by PGD2 and PGJ2 may play a role in the metabolic regulation of many mammalian cells [2].

Regulatory relationships of Ppia

• Cyclophilin A staining was present in both control and 2-methoxyethanol-treated rat testes in a stage-dependent manner, with pachytene spermatocytes in stage-VIII-XIV seminiferous tubules most heavily stained [7].

Other interactions of Ppia

• These results provide the first indication that cyclophilin-A participates in the activation of the caspase cascade in neuronal cells, in particular in the form of cascade elicited by excitotoxic stimuli [5].
• Cyclophilin A immunoreactivity was undetectable in glial fibrillary acidic protein (GFAP)-positive cells [10].
• Fluorescent double-labelling experiments on hippocampal cell cultures revealed that all cells labelled with the cyclophilin A antibody also showed staining for the neuron-specific marker for microtubule-associated protein (MAP)2, and could, therefore, be identified as neurons [10].
• Widely used control genes, GAPDH and beta-actin, were not included, although cyclophilin A was included [11].

Analytical, diagnostic and therapeutic context of Ppia

• Real-time RT-PCR was performed, with the cyclophilin A (CypA) mRNA level in each sample as an internal control [12].
• METHOD: The renal content and distribution of CypA was evaluated in untreated rats and in rats treated with a subcutaneous injection of CsA (10 mg. kg-1. day-1) for 10 days [9].
• The expression of the housekeeping gene, cyclophilin A was used to normalize total mRNA amounts and PCR conditions [13].

References