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91.
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93.
Rodríguez-Muñoz M Sánchez-Blázquez P Vicente-Sánchez A Bailón C Martín-Aznar B Garzón J 《Cellular and molecular life sciences : CMLS》2011,68(17):2933-2949
A series of pharmacological and physiological studies have demonstrated the functional cross-regulation between MOR and NMDAR.
These receptors coexist at postsynaptic sites in midbrain periaqueductal grey (PAG) neurons, an area implicated in the analgesic
effects of opioids like morphine. In this study, we found that the MOR-associated histidine triad nucleotide-binding protein
1 (HINT1) is essential for maintaining the connection between the NMDAR and MOR. Morphine-induced analgesic tolerance is prevented
and even rescued by inhibiting PKC or by antagonizing NMDAR. However, in the absence of HINT1, the MOR becomes supersensitive
to morphine before suffering a profound and lasting desensitization that is refractory to PKC inhibition or NMDAR antagonism.
Thus, HINT1 emerges as a key protein that is critical for sustaining NMDAR-mediated regulation of MOR signaling strength.
Thus, HINT1 deficiency may contribute to opioid-intractable pain syndromes by causing long-term MOR desensitization via mechanisms
independent of NMDAR. 相似文献
94.
95.
Important to the function of calpains is temporal and spatial regulation of their proteolytic activity. Here, we demonstrate
that cytoplasm-resident calpain 2 cleaves human nuclear topoisomerase I (hTOP1) via Ca2+-activated proteolysis and nucleoplasmic shuttling of proteases. This proteolysis of hTOP1 was induced by either ionomycin-caused
Ca2+ influx or addition of Ca2+ in cellular extracts. Ca2+ failed to induce hTOP1 proteolysis in calpain 2-knockdown cells. Moreover, calpain 2 cleaved hTOP1 in vitro. Furthermore,
calpain 2 entered the nucleus upon Ca2+ influx, and calpastatin interfered with this process. Calpain 2 cleavage sites were mapped at K158 and K183 of hTOP1. Calpain 2-truncated hTOP1 exhibited greater relaxation activity but remained able to interact with nucleolin and
to form cleavable complexes. Interestingly, calpain 2 appears to be involved in ionomycin-induced protection from camptothecin-induced
cytotoxicity. Thus, our data suggest that nucleocytoplasmic shuttling may serve as a novel type of regulation for calpain
2-mediated nuclear proteolysis. 相似文献
96.
The myogenic transcriptional network 总被引:2,自引:0,他引:2
97.
Khan ZU Martín-Montañez E Baxter MG 《Cellular and molecular life sciences : CMLS》2011,68(10):1737-1754
Visual perception and memory are the most important components of vision processing in the brain. It was thought that the
perceptual aspect of a visual stimulus occurs in visual cortical areas and that this serves as the substrate for the formation
of visual memory in a distinct part of the brain called the medial temporal lobe. However, current evidence indicates that
there is no functional separation of areas. Entire visual cortical pathways and connecting medial temporal lobe are important
for both perception and visual memory. Though some aspects of this view are debated, evidence from both sides will be explored
here. In this review, we will discuss the anatomical and functional architecture of the entire system and the implications
of these structures in visual perception and memory. 相似文献
98.
Naturally occurring antimicrobial peptides (AMPs) present several drawbacks that strongly limit their development into therapeutically
valuable antibiotics. These include susceptibility to protease degradation and high costs of manufacture. To overcome these
problems, researchers have tried to develop mimics or peptidomimetics endowed with better properties, while retaining the
basic features of membrane-active natural AMPs such as cationic charge and amphipathic design. Protein epitope mimetics, multimeric
(dendrimeric) peptides, oligoacyllysines, ceragenins, synthetic lipidated peptides, peptoids and other foldamers are some
of the routes explored so far. The synthetic approach has led to compounds that have already entered clinical evaluation for
the treatment of specific conditions, such as Staphylococcus (MRSA) infections. Should these trials be successful, an important proof-of-concept would be established, showing that synthetic
oligomers rather than naturally occurring molecules could bring peptide-based antibiotics to clinical practice and the drug
market for local and systemic treatment of medical conditions associated with multi-drug resistant pathogens. 相似文献
99.
Good MF 《Cellular and molecular life sciences : CMLS》2011,68(7):1105-1113
Malaria presents a challenge to world health that to date has been beyond the abilities of researchers to conquer. This critique
presents some of the strategies employed by the parasite to overcome immunity and the immunological challenges that we face
to develop vaccines. A conclusion is that a vaccine must identify novel antigens or epitopes that are not normally immunogenic
and which are therefore not under immune pressure and most likely to be conserved between different strains. Such antigens
are most likely to be targets of cellular immunity. The case for a whole parasite blood stage vaccine is presented based on
these premises. 相似文献
100.
Marsango S Bonaccorsi di Patti MC Barra D Miele R 《Cellular and molecular life sciences : CMLS》2011,68(17):2919-2929
Prokineticins are proteins that regulate diverse biological processes including gastrointestinal motility, angiogenesis, circadian
rhythm, and innate immune response. Prokineticins bind two closed related G-protein coupled receptors (GPCRs), PKR1 and PKR2.
In general, these receptors act as molecular switches to relay activation to heterotrimeric G-proteins and a growing body
of evidence points to the fact that GPCRs exist as homo- or heterodimers. We show here by Western-blot analysis that PKR2
has a dimeric structure in neutrophils. By heterologous expression of PKR2 in Saccharomyces cerevisiae, we examined the mechanisms of intermolecular interaction of PKR2 dimerization. The potential involvement of three types
of mechanisms was investigated: coiled-coil, disulfide bridges, and hydrophobic interactions between transmembrane domains.
Characterization of differently deleted or site-directed PKR2 mutants suggests that dimerization proceeds through interactions
between transmembrane domains. We demonstrate that co-expressing binding-deficient and signaling-deficient forms of PKR2 can
re-establish receptor functionality, possibly through a domain-swapping mechanism. 相似文献