Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pituitary adenylate cyclase activating polypeptide (PACAP) is a pleiotropic neuropeptide, exerting different actions in the central and peripheral nervous systems. Among others, it has neurotrophic and neuroprotective effects. In the present study, we investigated the effects of PACAP in a rat model of Parkinson's disease. Rats were given unilateral injections of 6-hydroxydopamine (6-OHDA) into the substantia nigra. PACAP-treated animals received 0.1 microg PACAP as a pretreatment. Control animals without PACAP treatment displayed severe hypokinesia at 1 and 10 days postlesion when compared to animals receiving saline only. In only 1 day postlesion, by contrast, PACAP-treated rats showed no hypokinesia. Asymmetrical signs, such as turning, rearing and biased thigmotaxic scanning were observed in all lesioned animals 1 day postlesion. PACAP-treated animals, however, showed better recovery as they ceased to display asymmetrical signs 10 days later and showed markedly less apomorphine-induced rotations. Tyrosine-hydroxylase immunohistochemistry revealed that control animals had more than 95% loss of the dopaminergic cells in the ipsilateral substantia nigra, while PACAP-treated animals had only approximately 50% loss of dopaminergic cells. In summary, the present results show the neuroprotective effect of PACAP in 6-OHDA-induced lesion of substantia nigra, with less severe acute neurological symptoms and a more rapid amelioration of behavioral deficits.
 ...
PMID:Pituitary adenylate cyclase activating polypeptide protects dopaminergic neurons and improves behavioral deficits in a rat model of Parkinson's disease. 1508 46

Na,K-ATPase is responsible for maintaining the correct concentrations of sodium and potassium in lens cells. Na,K-ATPase activity is different in the two cell types that make up the lens, epithelial cells and fibers; specific activity in the epithelium is higher than in fibers. In some parts of the fiber mass Na,K-ATPase activity is barely detectable. There is a large body of evidence that suggests Na,K-ATPase-mediated ion transport by the epithelium contributes significantly to the regulation of ionic composition in the entire lens. In some species different Na,K-ATPase isoforms are present in epithelium and fibers but in general, fibers and epithelium express a similar amount of Na,K-ATPase protein. Turnover of Na,K-ATPase by protein synthesis may contribute to preservation of high Na,K-ATPase activity in the epithelium. In ageing lens fibers, oxidation, and glycation may decrease Na,K-ATPase activity. Na,K-ATPase activity in lens fibers and epithelium also may be subject to regulation as the result of protein tyrosine phosphorylation. Moreover, activation of G protein-coupled receptors by agonists such as endothelin-1 elicits changes of Na,K-ATPase activity. The asymmetrical distribution of Na,K-ATPase activity in the epithelium and fibers may contribute to ionic currents that flow in and around the lens. Studies on human cataract and experimental cataract in animals reveal changes of Na,K-ATPase activity but no clear pattern is evident. However, there is a convincing link between abnormal elevation of lens sodium and the opacification of the lens cortex that occurs in age-related human cataract.
 ...
PMID:Expression, regulation and function of Na,K-ATPase in the lens. 1538 76

The ability of a cell to move requires the asymmetrical organization of cellular activities. To investigate polarized cellular activity in moving endothelial cells, human endothelial cells were incubated in a Dunn chamber to allow migration toward vascular endothelial growth factor. Immunofluorescent staining with a specific antibody against caveolin-1 revealed that caveolin-1 was concentrated at the rear of moving cells. Similarly, monolayer scraping to induce random cell walk resulted in relocation of caveolin-1 to the cell rear. These results suggest that posterior polarization of caveolin-1 is a common feature both for chemotaxis and chemokinesis. Dual immunofluorescent labeling showed that, during cell spreading, caveolin-1 was compacted in the cell center and excluded from nascent focal contacts along the circular lamellipodium, as revealed by integrin beta1 and FAK staining. When cells were migrating, integrin beta1 and FAK appeared at polarized lamellipodia, whereas caveolin-1 was found at the posterior of moving cells. Notably, wherever caveolin-1 was polarized, there was a conspicuous absence of lamellipod protrusion. Transmission electron microscopy showed that caveolae, similar to their marker caveolin-1, were located at the cell center during cell spreading or at the cell rear during cell migration. In contrast to its unphosphorylated form, tyrosine-phosphorylated caveolin-1, upon fibronectin stimulation, was associated with the focal complex molecule phosphopaxillin along the lamellipodia of moving cells. Thus, unphosphorylated and phosphorylated caveolin-1 were located at opposite poles during cell migration. Importantly, loss of caveolin-1 polarity by targeted down-regulation of the protein prevented cell polarization and directional movement. Our present results suggest a potential role of caveolin polarity in lamellipod extension and cell migration.
 ...
PMID:Loss of caveolin-1 polarity impedes endothelial cell polarization and directional movement. 1550 29

Pituitary adenylate cyclase activating polypeptide (PACAP) has several different actions in the nervous system, including neuroprotective effects. In the present study, we investigated the effects of different doses of PACAP on the functional and morphological outcome in a rat model of Parkinson's disease. Rats were given unilateral injections of 6-hydroxydopamine (6-OHDA) into the substantia nigra. PACAP-treated animals received 1, 0.1 or 0.01 microg PACAP as a pretreatment. Control animals without PACAP treatment displayed severe hypokinesia at 1 and 10 days post-lesion when compared to normal animals or those receiving saline only. PACAP treatment resulted in less severe acute hypokinesia, and complete recovery by 10 days. Asymmetrical signs were observed in all lesioned animals 1 day post-lesion. PACAP-treated animals, however, showed better recovery as they ceased to display asymmetrical signs 10 days later and showed markedly less apomorphine-induced rotations. Best behavioral outcome was observed in animals treated with 0.1 microg PACAP. Tyrosine-hydroxylase (TH) immunohistochemistry revealed increased number of dopaminergic neurons in the substantia nigra pars compacta and in the ventral tegmental area in all PACAP-treated rats in contrast to the severe cell loss in control animals. These results indicate that PACAP may be a promising therapeutic agent in Parkinson's disease.
 ...
PMID:Morphological and functional effects of PACAP in 6-hydroxydopamine-induced lesion of the substantia nigra in rats. 1551 97

The Tyr-X-X-Leu (YxxL) motif of the vaccinia virus F13L protein was examined for late (L) domain activity. The ability of an F13L deletion virus to form plaques was restored by PCR products containing single alanine substitutions within the motif and a YAAL construct but not by constructs lacking both the Y and L residues. Recombinant viruses possessing alanine substitutions in place of the tyrosine or the leucine residue in the YxxL motif demonstrated small, asymmetrical plaques. RNA interference-dependent depletion of Alix and TSG101 (host proteins involved in L domain-dependent protein trafficking) diminished extracellular enveloped virion production to various degrees, suggesting that the YxxL motif is a genuine L domain.
 ...
PMID:The vaccinia virus F13L YPPL motif is required for efficient release of extracellular enveloped virus. 1747 58

Uroporphyrinogen III synthase (U3S) catalyzes the asymmetrical cyclization of a linear tetrapyrrole to form the physiologically relevant uroporphyrinogen III (uro'gen III) isomer during heme biosynthesis. Here, we report four apoenzyme and one product complex crystal structures of the Thermus thermophilus (HB27) U3S protein. The overlay of eight crystallographically unique U3S molecules reveals a huge range of conformational flexibility, including a "closed" product complex. The product, uro'gen III, binds between the two domains and is held in place by a network of hydrogen bonds between the product's side chain carboxylates and the protein's main chain amides. Interactions of the product A and B ring carboxylate side chains with both structural domains of U3S appear to dictate the relative orientation of the domains in the closed enzyme conformation and likely remain intact during catalysis. The product C and D rings are less constrained in the structure, consistent with the conformational changes required for the catalytic cyclization with inversion of D ring orientation. A conserved tyrosine residue is potentially positioned to facilitate loss of a hydroxyl from the substrate to initiate the catalytic reaction.
 ...
PMID:Structure and mechanistic implications of a uroporphyrinogen III synthase-product complex. 1865 50

Preeclampsia is the major cause of maternal and fetal morbidity and mortality, involving 15% to 20% of pregnancies in developed countries and even more in less developed parts of the world. Superficial placentation driven by immune maladaptation, with subsequently reduced concentrations of angiogenic growth factors and increased placental debris in the maternal circulation, are likely responsible. Recent advances suggest that antiangiogenic factors (soluble fms-like tyrosine receptor kinase and soluble endoglin), altered relaxin-mediated mechanisms leading to impaired nitric oxide production through asymmetrical dimethylarginine production, and activating antibodies directed at the angiotensin II type 1 receptor may be responsible. The field of preeclampsia research is enjoying a well-deserved blossoming of novel ideas and approaches. We hope the activity will lead to much earlier diagnostic capacities and novel prophylactic treatments. The prize will go to the affected women and their afflicted children. For the investigators in the area, such a prize would be welcome.
 ...
PMID:Are we getting closer to a Nobel prize for unraveling preeclampsia? 1895 May 52

Protein degradation in the 20S proteasome is regulated in eukaryotes by the 19S ATPase complex and in archaea by the homologous PAN ATPase ring complex. Subunits of these hexameric ATPases contain on their C-termini a conserved hydrophobic-tyrosine-X (HbYX) motif that docks into pockets in the 20S to stimulate the opening of a gated substrate entry channel. Here, we report the crystal structure of the archaeal 20S proteasome in complex with the C-terminus of the archaeal proteasome regulatory ATPase, PAN. This structure defines the detailed interactions between the critical C-terminal HbYX motif and the 20S alpha-subunits and indicates that the intersubunit pocket in the 20S undergoes an induced-fit conformational change on binding of the HbYX motif. This structure together with related mutagenesis data suggest how in eukaryotes certain proteasomal ATPases bind to specific pockets in an asymmetrical manner to regulate gate opening.
 ...
PMID:Interactions of PAN's C-termini with archaeal 20S proteasome and implications for the eukaryotic proteasome-ATPase interactions. 2001 67

The complete three-dimensional sensory module structures of the Pr ground state of Synechocystis 6803 Cph1 and the unusual Pfr ground state of the bacteriophytochrome PaBphP (PDB codes 2VEA and 3C2W respectively) have now been solved, revealing an asymmetrical dumbbell form made up of a PAS (Period/ARNT/Singleminded)-GAF (cGMP phosphodiesterase/adenylate cyclase/FhlA) bidomain carrying the chromophore and the smaller PHY (phytochrome-specific) domain. The PHY domain is structurally related to the GAF family, but carries an unusual tongue-like structure which contacts the larger lobe to seal the chromophore pocket. In 2VEA, the tongue makes intimate contact with the helical N-terminus; both the N-terminus and the tongue structures are quite different in 3C2W. As expected, the structures reveal ZZZssa and ZZEssa chromophore conformations in 2VEA and 3C2W respectively, associated with tautomeric differences in several nearby tyrosine residues. Two salt bridges on opposite sides of the chromophore, as well as the associations of the C-ring propionates also differ. It is still unclear, however, which of these structural differences are associated with bacteriophytochromes compared with Cph1 and plant-type phytochromes, the unusual 3C2W Pfr ground state functionality compared with the Pr ground state or the Pr compared with Pfr photoisomerism. To access the latter unambiguously, both Pr and Pfr structures of the same molecule are required. New solid-phase NMR data for Cph1 in the Pr, Pfr and freeze-trapped intermediate states reveal unexpected changes in the chromophore during Pfr-->Pr photoconversion. These, together with our efforts to solve the three-dimensional structure of a complete phytochrome molecule are also described.
 ...
PMID:Phytochrome three-dimensional structures and functions. 2029 48

Hyperactivation, a swimming pattern of mammalian sperm in the oviduct, is essential for fertilization. It is characterized by asymmetrical flagellar beating and an increase of cytoplasmic Ca(2+). We observed that some mouse sperm swimming in the oviduct produce high-amplitude pro-hook bends (bends in the direction of the hook on the head), whereas other sperm produce high-amplitude anti-hook bends. Switching direction of the major bends could serve to redirect sperm toward oocytes. We hypothesized that different Ca(2+) signaling pathways produce high-amplitude pro-hook and anti-hook bends. In vitro, sperm that hyperactivated during capacitation (because of activation of CATSPER plasma membrane Ca(2+) channels) developed high-amplitude pro-hook bends. The CATSPER activators procaine and 4-aminopyridine (4-AP) also induced high-amplitude pro-hook bends. Thimerosal, which triggers a Ca(2+) release from internal stores, induced high-amplitude anti-hook bends. Activation of CATSPER channels is facilitated by a pH rise, so both Ca(2+) and pH responses to treatments with 4-AP and thimerosal were monitored. Thimerosal triggered a Ca(2+) increase that initiated at the base of the flagellum, whereas 4-AP initiated a rise in the proximal principal piece. Only 4-AP triggered a flagellar pH rise. Proteins were extracted from sperm for examination of phosphorylation patterns induced by Ca(2+) signaling. Procaine and 4-AP induced phosphorylation of proteins on threonine and serine, whereas thimerosal primarily induced dephosphorylation of proteins. Tyrosine phosphorylation was unaffected. We concluded that hyperactivation, which is associated with capacitation, can be modulated by release of Ca(2+) from intracellular stores to reverse the direction of the dominant flagellar bend and, thus, redirect sperm.
 ...
PMID:Two distinct Ca(2+) signaling pathways modulate sperm flagellar beating patterns in mice. 2138 47


<< Previous 1 2 3 4 Next >>