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31.
Certain drugs and chemicals, such as chloroquine, chlorpromazine, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), are bound to melanin and retained in pigment cells for long periods. This specific retention in pigmented tissues can cause adverse effects in the skin, eye, inner ear, and pigmented nerve cells of the substantia nigra of the brain. To date, all studies have been focused on eu- and neuromelanin. In the present study, we show that chloroquine, chlorpromazine, chlomipramine, paraquat, acridine orange, and nickel, which are bound to eumelanin, also bind to synthetic pheomelanin, but the binding to pheomelanin is lower. The binding varied with the cysteine content and pH, and the results indicate that the binding is complex and includes ionic interactions. In addition, we have shown that these substances also bind to synthetic thiourea-containing melanin, but to quite a low extent. We also present a microautoradiographic study on the binding of 14C-chloroquine to natural pheomelanin in vivo in yellow mice C57BL (Ay/a). Black (C57/BL) and albino (NMRI) mice were used as controls. The autoradiography demonstrated a pronounced uptake of chloroquine in the hair follicles and the dermal melanocytes in the ear of yellow mice, which was comparable to the corresponding accumulation of label in black mice. In the albino mouse, the uptake was lower and more homogeneously distributed in the skin. These results suggest that the toxicologi-cal risks of melanin-related adverse effects are applicable to persons with a high content of pheomelanin in the skin and hair. 相似文献
32.
SV40 large T antigen has been reported to be modified with several
different sugars including N-acetylglucosamine, galactose, and mannose. In
this report we have reexamined the glycosylation of T antigen and found
that while we could detect modification with N-acetylglucosamine, we could
not detect any other sugars on the protein. Surprisingly, even though
[3H]galactose could be metabolically incorporated into the protein,
analysis showed that all of the radioactivity in T antigen had been
converted to other species. The N-acetylglucosamine was demonstrated to be
linked to the protein in the form of O-linked N- acetylglucosamine, the
best characterized form of nuclear and cytoplasmic glycosylation in
mammalian systems. We have localized the major site of glycosylation to the
amino terminal portion of the molecule. Analysis of mutated T antigen where
serines 111/112 were substituted with alanine suggest that these residues
constitute a glycosylation site on the protein. These two serines fall
within a typical O-linked N-acetylglucosamine glycosylation site (PSS) and
are also known to be phosphorylated. Thus, it is likely that competition
between phosphorylation and glycosylation occurs at this site.
相似文献
33.
34.
35.
Dana Berner Farivar Eskandari Craig Cavin H.J. Dubin 《Biocontrol Science and Technology》2015,25(6):732-737
Koch's postulates were fulfilled on five geographical accessions of Lepidium draba and preliminary host range tests were conducted with Septoria lepidii Desm. on 42 Brassicaceae species. Host range results showed the fungus specific to Lepidium spp. This fungus is potentially an important biological control agent for weedy species of Lepidium. 相似文献
36.
Background
Modeling of transmembrane domains (TMDs) requires correct prediction of interfacial residues for in-silico modeling and membrane insertion studies. This implies the defining of a target sequence long enough to contain interfacial residues. However, too long sequences induce artifactual polymorphism: within tested modeling methods, the longer the target sequence, the more variable the secondary structure, as though the procedure were stopped before the end of the calculation (which may in fact be unreachable). Moreover, delimitation of these TMDs can produce variable results with sequence based two-dimensional prediction methods, especially for sequences showing polymorphism. To solve this problem, we developed a new modeling procedure using the PepLook method. We scanned the sequences by modeling peptides from the target sequence with a window of 19 residues.Results
Using sequences whose NMR-structures are already known (GpA, EphA1 and Erb2-HER2), we first determined that the hydrophobic to hydrophilic accessible surface area ratio (ASAr) was the best criterion for delimiting the TMD sequence. The length of the helical structure and the Impala method further supported the determination of the TMD limits. This method was applied to the IL-2Rβ and IL-2Rγ TMD sequences of Homo sapiens, Rattus norvegicus, Mus musculus and Bos taurus.Conclusions
We succeeded in reducing the variation in the TMD limits to only 2 residues and in gaining structural information. 相似文献37.
Over the past decade, there have been many reports suggesting the presence
of complex carbohydrates on nuclear and cytoplasmic proteins in mammalian
cells. Some of the most often cited of these reports deal with the
glycosylation of the high mobility group (HMG) proteins. These are
relatively abundant chromosomal proteins that are known to be associated
with nucleosomes and actively transcribed regions of chromatin. The
original report describing HMG protein glycosylation presented several
lines of evidence suggesting that these proteins are glycosylated,
including carbohydrate compositional analysis and periodic-acid Schiff
staining. We have attempted to repeat these observations with more highly
purified protein than was utilized in the original study. Using
carbohydrate compositional analysis performed by high pH anion exchange
chromatography coupled to pulsed-amperometric detection, we saw no evidence
for significant glycosylation of these proteins. In addition, we found no
evidence for the presence of O- GlcNAc, a well known form of nuclear
glycosylation. The HMG proteins did react with periodate, suggesting the
presence of a modification containing cis-diols on the protein. Several
tryptic peptides isolated from HMG 14 and 17 which retained the periodate
reactivity had in common lysine residues, suggesting a potential
modification of the straightepsilon-amino groups of lysines such as
nonenzymatic glycation. Western blot analysis of the HMG proteins using
anti-advanced glycation endproducts (AGE) antibodies confirmed the presence
of glycation products on the HMG proteins.
相似文献
38.
RS Redman 《Biotechnic & histochemistry》2013,88(3-4):103-130
Radiation therapy for cancer of the head and neck can devastate the salivary glands and partially devitalize the mandible and maxilla. As a result, saliva production is drastically reduced and its quality adversely altered. Without diligent home and professional care, the teeth are subject to rapid destruction by caries, necessitating extractions with attendant high risk of necrosis of the supporting bone. Innovative techniques in delivery of radiation therapy and administration of drugs that selectively protect normal tissues can reduce significantly the radiation effects on salivary glands. Nonetheless, many patients still suffer severe oral dryness. I review here the functional morphology and development of salivary glands as these relate to approaches to preventing and restoring radiation-induced loss of salivary function. The acinar cells are responsible for most of the fluid and organic material in saliva, while the larger ducts influence the inorganic content. A central theme of this review is the extent to which the several types of epithelial cells in salivary glands may be pluripotential and the circumstances that may influence their ability to replace cells that have been lost or functionally inactivated due to the effects of radiation. The evidence suggests that the highly differentiated cells of the acini and large ducts of mature glands can replace themselves except when the respective pools of available cells are greatly diminished via apoptosis or necrosis owing to severely stressful events. Under the latter circumstances, relatively undifferentiated cells in the intercalated ducts proliferate and redifferentiate as may be required to replenish the depleted pools. It is likely that some, if not many, acinar cells may de-differentiate into intercalated duct-like cells and thus add to the pool of progenitor cells in such situations. If the stress is heavy doses of radiation, however, the result is not only the death of acinar cells, but also a marked decline in functional differentiation and proliferative capacity of all of the surviving cells, including those with progenitor capability. Restoration of gland function, therefore, seems to require increasing the secretory capacity of the surviving cells, or replacing the acinar cells and their progenitors either in the existing gland remnants or with artificial glands. 相似文献
39.
K Ramamoorthy Subramanian Raghunandhakumar RS Anand A Paramasivam S Kamaraj S Nagaraj Devaraj Ezhilarasan Thangavelu Lakshmi Kamal Dua Dinesh Kumar Chellappan Ashokkumar Veeramuthu 《Bioinformation》2020,16(11):965
Astaxanthin (AXN) is known to have health benefits by epidemiological studies. Therefore, it is of interest to assess the effect of AXN (derived from indigenous unicellular green alga Haematococcus lacustris) to modulate cell cycle arrest, lysosomal acidification and eventually apoptosis using in vitro in A549 lung cancer cells. Natural extracts of astaxanthin were obtained by standardized methods as reported earlier and characterized by standard HPLC and MS. Treatment of A549 cells with AXN (purified fraction) showed significant reduction in cell viability (about 50%) as compared to crude extract at 50µM concentration. Thus, we show the anticancer effects and lysosomal acidification in A549 cells by Astaxanthin from Haematococcus lacustris for further consideration. Together, our results demonstrated the anticancer potential of AXN from Haematococcus lacustris, which is found to be mediated via its ability to induce cell cycle arrest, lysosomal acidification and apoptotic induction. 相似文献
40.
Youn Tae Kwak Alexa Raney Lillian S Kuo Sarah J Denial Brenda RS Temple J Victor Garcia John L Foster 《Retrovirology》2010,7(1):1-22