Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The properties of a ryanodine-sensitive Ca2+ release channel (receptor) in non-excitable cells like exocrine cells or epithelial cells are described in this review. The ryanodine-sensitive Ca2+ release from the microsomal vesicles is activated by Ca2+, caffeine, ryanodine or cyclic ADP-ribose (cADPR) and is inhibited by ruthenium red or higher concentrations (> or =100 microM) of ryanodine. The properties are similar to those of excitable cells such as muscle cells or neuronal tissues. In some non-excitable cells, the Ca2+ release induced by caffeine, ryanodine or cADPR is stimulated by calmodulin (CaM) or FK506. Kd values of [3H]ryanodine binding to the receptor protein range from 6 to 17 nM and are similar to those of a high-affinity binding site in skeletal or cardiac muscle. Maximum binding capacities (Bmax) range from 40 to 620 fmol/ mg protein and are 10 approximately 200-fold lower than those for a high-affinity binding site in skeletal muscle. Caffeine, adenine nucleotide AMP-PCP, Mg2+, ruthenium red or FK506 affects the binding. In some non-excitable cells, the ryanodine receptor (RyR) isoform RyR2 or RyR3 is expressed and has been identified. However, unlike for excitable cells, information concerning the RyR proteins, including binding sites for modulators like CaM and phosphorylation sites has not yet been obtained.
 ...
PMID:Ryanodine-sensitive Ca2+ release mechanism in non-excitable cells (Review). 1111 3

Infection with the opportunistic fungal pathogen, Pneumocystis jirovecii causes life-threatening pneumonia in immunocompromised individuals. In addition to HIV-1 infected patients, individuals at risk of Pneumocystis infection include those receiving immunosuppressive therapies due to transplantation, cancer or autoimmune disease. Antibiotic treatment is not always successful, and it does not prevent obstructive lung disease after clearance of the pathogen. Therefore, it is essential to develop therapeutic alternatives that are more effective against PCP. We reported that Pneumocystis recombinant protein KEX1 induces protective immunity against the development of PCP in a non-human primate model of HIV-induced immunosuppression. In this study, we tested the immunogenicity KEX1 immunization of healthy rhesus macaques and the durability of these responses during drug-induced immunosuppression using tacrolimus (FK506) and methylprednisolone. We observed that vaccination with KEX1 prior to the start of the immunosuppressive regimen generated a robust and long-lasting antibody response that was maintained throughout the immunosuppressive treatment. Furthermore, boosting with KEX1 during immunosuppression induced recall of memory responses against recombinant KEX1. The durability of the anti-KEX1 response and the ability to induce a recall response during immunosuppressive therapy provide a proof-of-concept data supporting further investigation of the KEX1 as a prophylactic vaccine to prevent PCP in drug-induced immunosuppression. This approach provides fundamental knowledge for the elaboration of therapeutic and prophylactic alternatives for PCP in patients undergoing severe immunosuppressive therapy.
 ...
PMID:Immunization with Pneumocystis recombinant KEX1 induces robust and durable humoral responses in immunocompromised non-human primates. 3284 Apr 16