Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effect of (2'-5')oligoadenylate (2-5A) on cellular and viral protein and RNA syntheses was investigated with two mouse cell lines, L929 and Lz (a subclone of L929). The oligonucleotide was introduced into the cells either by using calcium phosphate coprecipitation technique or by microinjection method. In L929 cells protein and viral RNA syntheses were severely inhibited by 2-5A, whereas in Lz cells, both were only slightly inhibited. The activities of 2-5A synthetase and double-stranded (ds)RNA-dependent protein kinase were enhanced by interferon (IFN) treatment roughly to the same extent and there was no significant difference in the level of 2'-5' phosphodiesterase activity either. On the other hand, 2-5A-dependent RNase (RNase L) activity in Lz cells was low, being about 10-20% of that of L929 cells. It was increased twofold after IFN treatment, but protein synthesis of Lz cells was not as sensitive to 2-5A as that of L929 cells even after IFN treatment. L929 and Lz cells were sensitive to the antiviral effect of mouse IFN against vesicular stomatitis virus (VSV) and Mengovirus. In contrast, however, Lz cells were relatively insensitive to the antiviral effect of IFN on vaccinia virus, whereas L929 cells were sensitive.
 ...
PMID:Comparative studies on (2'-5')oligoadenylate-related enzyme systems and the antiviral effect of interferon in two mouse cell lines which differ in (2'-5')oligoadenylate sensitivity of their protein synthesizing system. 241 28

Injury of peripheral nerves induces expression of several pro-protein convertases (PCs) involved in processing of precursor proteins into their diverse active end-products. In this study, the focus was on convertase PC1 which, although undetectable in control nerves, is strongly induced in injured nerves. High concentrations of PC1 mRNA of 9.0, 5.5, 3.0, 2.5 and 1.6 kb were observed on day 4 post-lesion in proximal and distal segments. By in situ hybridization PC1 mRNA was detected in most of endoneurial cells, which were further identified by immunocytochemistry as myelin 2', 3'-cyclic nucleotide 3'-phosphodiesterase containing Schwann cells. PC1 mRNA and protein were also present in cultured Schwann cells also containing convertases PC5, furin and PC7 as well as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Mostly unprocessed pro-NGF of 35 kDa and pro-BDNF of 35 kDa were found on Western blotting of Schwann cells. Expression of exogenous neurotrophins by infection with vaccinia virus vector showed that mouse pro-NGF and rat pro-BDNF are cleaved intracellularly on smaller forms of 13.5 kDa NGF and 14 kDa BDNF. Infection experiments demonstrated that Schwann cells contain active processing enzymes. In conclusion, this work provides in vivo evidence of the presence of several PCs in the injured rat sciatic nerve and ex vivo in cultured Schwann cells.
 ...
PMID:The pro-protein convertase PC1 is induced in the transected sciatic nerve and is present in cultured Schwann cells: comparison with PC5, furin and PC7, implication in pro-BDNF processing. 972 4

Poxviruses appear to use single-strand annealing reactions to recombine linear molecules sharing short (<20 bp) regions of end homology. We have examined the effect of base mismatches and base insertions on the reaction efficiency and used mismatch-containing DNAs to further characterize the polarity of the exonuclease postulated to catalyze these reactions in vivo. Incorporating one or two base substitutions within the 20-bp segment of end homology had little effect on virus-promoted recombination, reducing the frequency of recombinational repair of transfected plasmids only 10-20%. Base insertions were more destabilizing and their presence inhibited recombination 40% (with one insertion) and 75% (with two). The sequence of the recombinants recovered from virus-infected and transfected cells suggested that hybrid DNA is usually formed and then resolved by replication without repair. However, a few of the joints retained sequences suggestive of more complex enzymatic processing in vivo. We also used transfection studies to examine the fate of each of the four strands processed by the vaccinia recombination machinery. The preferential retention of base substitutions located near each of the 5'-ended strands confirmed that virus single-strand annealing reactions are catalyzed primarily by a 3'- to 5'-exonuclease. Other studies showed that mismatch repair reactions do not invalidate these conclusions, even though base excision repair systems are seemingly active and preferentially convert T. G and C. A mismatches to CG base pairs in vaccinia-infected cells.
 ...
PMID:Characterization of the recombinant joints formed by single-strand annealing reactions in vaccinia virus-infected cells. 1270 98

Several neurodegenerative disorders, such as multiple sclerosis, Alzheimer's disease, and Parkinson's disease, are associated with inflammatory damage. The complex process of neuroinflammation involves various components of the immune system and the central nervous system. Particularly, brain astrocytes and microglial cells generate several inflammatory mediators like cytokines, leukotrienes, superoxide radicals, eicasonoids, and the components of the complement cascade. Complement plays an important role in the etiology of most of the neuroinflammatory disorders. To prevent long-term dysfunction inflammation in the central nervous system must be modulated with neuroprotective agents such as nonsteroidal anti-inflammatory drugs, steroids, phenolic thiazoles, nitrones, catechins, nitric oxide synthetase inhibitors, flavonoids, and phosphodiesterase inhibitors. Few drugs are found to be effective and their therapeutic benefit is hampered by side effects. Most of the neuroprotective agents are free radical scavengers and many inhibit only one or two aspects of inflammation. The complement inhibitory activity of most of these agents is either unknown or not established. Thus, there is doubt regarding their therapeutic value in most of the inflammatory disorders in which complement plays a major role. In this context the role of a multifunctional protein, vaccinia virus complement control protein (VCP), is quite significant as it may play a pivotal role in the treatment of several neuroinflammatory disorders. VCP is known to inhibit both complement pathways involved in inflammation. It is also known to inhibit cytokines and chemokines in inflammation. Our recent studies on rats demonstrate that VCP administration inhibits macrophage infiltration, reduces spinal cord destruction, and improves motor skills associated with spinal cord injury, establishing VCP as a strong candidate for neuroprotection. Thus, complement inhibitors such as VCP can serve as neuroprotective agents in inflammation associated with several neurodegenerative disorders.
 ...
PMID:Neuroprotection from complement-mediated inflammatory damage. 1568 6