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271.
Pitcher RS Green AJ Brzostek A Korycka-Machala M Dziadek J Doherty AJ 《DNA Repair》2007,6(9):1271-1276
The physiological role of the non-homologous end-joining (NHEJ) pathway in the repair of DNA double-strand breaks (DSBs) was examined in Mycobacterium smegmatis using DNA repair mutants (DeltarecA, Deltaku, DeltaligD, Deltaku/ligD, DeltarecA/ku/ligD). Wild-type and mutant strains were exposed to a range of doses of ionizing radiation at specific points in their life-cycle. NHEJ-mutant strains (Deltaku, DeltaligD, Deltaku/ligD) were significantly more sensitive to ionizing radiation (IR) during stationary phase than wild-type M. smegmatis. However, there was little difference in IR sensitivity between NHEJ-mutant and wild-type strains in logarithmic phase. Similarly, NHEJ-mutant strains were more sensitive to prolonged desiccation than wild-type M. smegmatis. A DeltarecA mutant strain was more sensitive to desiccation and IR during both stationary and especially in logarithmic phase, compared to wild-type strain, but it was significantly less sensitive to IR than the DeltarecA/ku/ligD triple mutant during stationary phase. These data suggest that NHEJ and homologous recombination are the preferred DSB repair pathways employed by M. smegmatis during stationary and logarithmic phases, respectively. 相似文献
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273.
Marta A. Uzarska Igor Grochowina Joanna Soldek Marcin Jelen Brenda Schilke Jaroslaw Marszalek Elizabeth A. Craig Rafal Dutkiewicz 《The Journal of biological chemistry》2022,298(2)
In mitochondria, cysteine desulfurase (Nfs1) plays a central role in the biosynthesis of iron–sulfur (FeS) clusters, cofactors critical for activity of many cellular proteins. Nfs1 functions both as a sulfur donor for cluster assembly and as a binding platform for other proteins functioning in the process. These include not only the dedicated scaffold protein (Isu1) on which FeS clusters are synthesized but also accessory FeS cluster biogenesis proteins frataxin (Yfh1) and ferredoxin (Yah1). Yfh1 has been shown to activate cysteine desulfurase enzymatic activity, whereas Yah1 supplies electrons for the persulfide reduction. While Yfh1 interaction with Nfs1 is well understood, the Yah1–Nfs1 interaction is not. Here, based on the results of biochemical experiments involving purified WT and variant proteins, we report that in Saccharomyces cerevisiae, Yah1 and Yfh1 share an evolutionary conserved interaction site on Nfs1. Consistent with this notion, Yah1 and Yfh1 can each displace the other from Nfs1 but are inefficient competitors when a variant with an altered interaction site is used. Thus, the binding mode of Yah1 and Yfh1 interacting with Nfs1 in mitochondria of S. cerevisiae resembles the mutually exclusive binding of ferredoxin and frataxin with cysteine desulfurase reported for the bacterial FeS cluster assembly system. Our findings are consistent with the generally accepted scenario that the mitochondrial FeS cluster assembly system was inherited from bacterial ancestors of mitochondria. 相似文献
274.
Jaroslaw Baran Monika Baj-Krzyworzeka Kazimierz Weglarczyk Rafal Szatanek Maria Zembala Jakub Barbasz Antoni Czupryna Antoni Szczepanik Marek Zembala 《Cancer immunology, immunotherapy : CII》2010,59(6):841-850
Cell membrane microfragments called microvesicles (MV) originating from different cells are circulating in the blood of healthy
subjects and their elevated numbers are found in different diseases, including cancer. This study was designed to characterise
MV present in plasma of gastric cancer patients. Since majority of MV in blood are platelets-derived (PMV), plasma samples
deprived of PMV were used. In comparison to control, the number of MV in patients was significantly elevated in all stages,
higher in more advanced disease. Patients’ MV showed an increased membrane expression of CCR6 and HER-2/neu. The proportion
of MV carrying some leucocyte determinants was low and similar in patients and control. Transmission electron microscopy showed
their substantial heterogeneity in size and shape. The size determined by dynamic light scattering analysis confirmed this
heterogeneity. The MV size distribution in patients was broader within the range of 10–800 nm, while in control MV showed
3-mode distribution within the range of 10–400 nm. Atomic force microscopy confirmed MV size heterogeneity with implication
that larger objects represented aggregates of smaller microparticles. Patients’ MV exhibited increased absolute values of
zeta potential, indicating a higher surface charge. Tumour markers HER-2/neu, MAGE-1, c-MET and EMMPRIN were detected both
in control and patients’ samples with stronger expression in the latter. Significantly higher expression of MAGE-1 and HER-2/neu
mRNA was observed in individual patients. All together, it suggests that at least some MV in plasma of gastric cancer patients
are tumour-derived. However, their role in cancer requires further studies. 相似文献
275.
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277.
Anna Wojakowska ?ukasz Marczak Karol Jelonek Krzysztof Polanski Piotr Widlak Monika Pietrowska 《PloS one》2015,10(9)
Formalin-fixed paraffin-embedded (FFPE) tissue specimens constitute a highly valuable source of clinical material for retrospective molecular studies. However, metabolomic assessment of such archival material remains still in its infancy. Hence, there is an urgent need for efficient methods enabling extraction and profiling of metabolites present in FFPE tissue specimens. Here we demonstrate the methodology for isolation of primary metabolites from archival tissues; either fresh-frozen, formalin-fixed or formalin-fixed and paraffin-embedded specimens of mouse kidney were analysed and compared in this work. We used gas chromatography followed by mass spectrometry (GC/MS approach) to identify about 80 metabolites (including amino acids, saccharides, carboxylic acids, fatty acids) present in such archive material. Importantly, about 75% of identified compounds were detected in all three types of specimens. Moreover, we observed that fixation with formalin itself (and their duration) did not affect markedly the presence of particular metabolites in tissue-extracted material, yet fixation for 24h could be recommended as a practical standard. Paraffin embedding influenced efficiency of extraction, which resulted in reduced quantities of several compounds. Nevertheless, we proved applicability of FFPE specimens for non-targeted GS/MS-based profiling of tissue metabolome, which is of great importance for feasibility of metabolomics studies using retrospective clinical material. 相似文献
278.
Ovarian originated oxytocin (OT) is involved in several reproductive process, amongst them its role in the regulation/modulation of the estrous cycle in several species has been demonstrated. Although the systemic role of endometrial originated prostaglandins (PGs), especially prostaglandin F(2α) (PGF(2α)), is equivocal in cats, their possible involvement in the local regulation of uterine events during the estrous cycle is uncertain. We examined the spontaneous and LH-stimulated OT production in cultured luteal cells, the spatial and temporal arrangement of OT receptors (OTR) in a cat endometrium and, finally the effects of OT on PG secretion and prostaglandin-endoperoxide synthase (PTGS2) expression in the feline cultured endometrial cells. Uteri together with ovaries were collected from adult domestic cats (n=27) at different stages of the estrous cycle, after routine ovariohysterectomy procedures. The endometrial and luteal cells were separated enzymatically. Luteinizing hormone (LH) augmented OT secretion in cultured luteal cells 2-fold compared with control (P<0.05). Oxytocin receptor was abundantly expressed in different ovarian structure, as well as in uterine tissues collected at early/developing and mid-luteal phase. The secretion of PGF(2α) by endometrial epithelial cells was increased by OT at a dose 10(-7)M (P<0.001). Atosiban (specific OTR blocker) alone did not affect PG secretion but atosiban in combination with OT abolished the stimulating effect of OT on PGF(2α) secretion. Oxytocin augmented PGE(2) secretion at a dose 10(-7)M and 10(-6)M in the endometrial stromal cells (P<0.001). The treatment with atosiban did not abrogated positive effect of OT on PGE(2) production in the stromal cells. Effect of OT on PTGS2 mRNA expression, the rate-limiting enzyme in PG production, was examined by Real Time-PCR and PTGS2 mRNA expression was significantly affected by OT in both epithelial and stromal cell cultures (P<0.01). The present observations have shown that OT is locally produced by the early/developing corpora lutea and that corpora lutea delivered OT may regulate PG secretion in a cat endometrium especially at early- and mid-diestrus, by affecting PTGS2 mRNA expression. 相似文献
279.
Cochran R Kalisiak J Küçükkilinç T Radic Z Garcia E Zhang L Ho KY Amitai G Kovarik Z Fokin VV Sharpless KB Taylor P 《The Journal of biological chemistry》2011,286(34):29718-29724
The cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase, are primary targets of organophosphates (OPs). Exposure to OPs can lead to serious cardiovascular complications, respiratory compromise, and death. Current therapy to combat OP poisoning involves an oxime reactivator (2-PAM, obidoxime, TMB4, or HI-6) combined with atropine and on occasion an anticonvulsant. Butyrylcholinesterase, administered in the plasma compartment as a bio-scavenger, has also shown efficacy but is limited by its strict stoichiometric scavenging, slow reactivation, and a propensity for aging. Here, we characterize 10 human (h) AChE mutants that, when coupled with an oxime, give rise to catalytic reactivation and aging resistance of the soman conjugate. With the most efficient human AChE mutant Y337A/F338A, we show enhanced reactivation rates for several OP-hAChE conjugates compared with wild-type hAChE when reactivated with HI-6 (1-(2'-hydroxyiminomethyl-1'-pyridinium)-3-(4'-carbamoyl-1-pyridinium)). In addition, we interrogated an 840-member novel oxime library for reactivation of Y337A/F338A hAChE-OP conjugates to delineate the most efficient oxime-mutant enzyme pairs for catalytic bio-scavenging. Combining the increased accessibility of the Y337A mutation to oximes within the space-impacted active center gorge with the aging resistance of the F338A mutation provides increased substrate diversity in scavenging potential for aging-prone alkyl phosphate inhibitors. 相似文献
280.