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91.
92.
Andreas Gescher Maurizio DIncalci Roberto Fanelli Pierluigi Farina 《Life sciences》1980,26(2):147-154
N-Hydroxymethylpentamethylmelamine (HMPMM) was identified by HPLC and by GLC-MS after derivatization, as a metabolite of the anticancer drug hexamethylmelamine (HMM) in incubation mixtures with fortified mouse liver 9000 × g and microsomal preparations. HMPMM formation was dependent on the presence of NADPH and oxygen. N-demethylated metabolites were also found. HMPMM displays appreciable chemical stability and 29% was recovered after 60 min incubation in buffer. HMPMM constituted more than 50% of total HMM metabolites in 30 min incubations. The known chemical reactivity of carbinolamines means that HMPMM could be involved in the pharmacological or toxic effects of HMM. 相似文献
93.
94.
Decellularized colorectal cancer matrix as bioactive microenvironment for in vitro 3D cancer research 下载免费PDF全文
95.
The 5′-adenosine monophosphate-activated protein kinase (AMPK) is a key regulator of the cellular energy metabolism and may induce either cell survival or death. We previously reported that in SH-SY5Y human neuroblastoma cells stimulation of muscarinic acetylcholine receptors (mAChRs) activate AMPK by triggering store-operated Ca2+ entry (SOCE). However, whether mAChRs may control AMPK activity by regulating additional mechanisms beyond SOCE remains to be investigated. In the present study we examined the effects of mAChRs on AMPK when SOCE was induced by the sarco–endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin. We found that in SH-SY5Y cells depleted of Ca2+ by thapsigargin, the re-addition Ca2+ to the medium stimulated AMPK phosphorylation at Thr172, which is required for full kinase activity. This response occurred through SOCE, as it was blocked by either the SOCE modulator 2-aminoethoxydiphephenyl borate, knockdown of the SOCE molecular component STIM1, or inhibition of Ca2+/calmodulin (CaM)-dependent protein kinase kinase β (CaMKKβ). In thapsigargin-pretreated cells, stimulation of pharmacologically defined M3 mAChRs potentiated SOCE-induced AMPK activation. This potentiation did not involve an increased Ca2+ influx, but was associated with CaM mobilization from membrane to cytosol, increased CaM/CaMKKβ interaction, and enhanced CaMKK stimulation by thapsigargin-induced SOCE. In thapsigargin-pretreated cells Ca2+ re-addition stimulated glucose uptake and increased the membrane expression of the glucose transporter GLUT1. Both responses were significantly potentiated by mAChRs. These data indicate that in human neuroblastoma cells mAChRs up-regulate AMPK and the downstream glucose uptake by triggering not only SOCE but also CaM translocation and enhanced formation of active CaM/CaMKKβ complexes. 相似文献
96.
Structure and absolute stereochemistry of vanillosmin,a guaianolide from Vanillosmopsis erythropappa
Attilio Corbrella Pierluigi Gariboldi Giancarlo Jommi Fulvia Orsini Giorgio Ferrari 《Phytochemistry》1974,13(2):459-465
The structure and absolute stereochemistry of vanillosmin were established by chemical and spectral evidence and by comparison with O-acetyl-isophoto-α-santonic lactone and tetrahydroartabsin “C”. 相似文献
97.
QUANTITATIVE AUTORADIOGRAPHIC STUDY OF LABELED RNA IN RABBIT OPTIC NERVE AFTER INTRAOCULAR INJECTION OF [3H]URIDINE 总被引:1,自引:1,他引:0 下载免费PDF全文
Pierluigi Gambetti Lucila Autilio-Gambetti Brenda Shafer LaDorna Pfaff 《The Journal of cell biology》1973,59(3):677-684
The distribution of labeled RNA in the optic nerve of the rabbit was studied by quantitative ultrastructural autoradiography after the intraocular injection of [3H]uridine. The highest density of silver grains related to [3H]RNA (27–40 grains/100 µm2) was found in glial cell perikarya; a slightly lower density was present in the glial nuclei (19–20 grains/100 µm2). Axons (4–5 grains/100 µm2) and myelin (2–3 grains/100 µm2) had the lowest grain densities. 74–83% of all counted grains were located outside the axons. By comparing the grain density distribution over the axon with that expected in the case of an exclusive labeling of the surrounding myelin and glial cell processes, it was concluded that the axons contained a number of grains representing [3H]RNA significantly higher than that expected to scatter from myelin and glial processes. Most of these grains were concentrated at the periphery of the axon and were not related to axonal mitochondria. 相似文献
98.
THE FINE STRUCTURE OF PUROMYCIN-INDUCED CHANGES IN MOUSE ENTORHINAL CORTEX 总被引:8,自引:2,他引:6 下载免费PDF全文
Pierluigi Gambetti Nicholas K. Gonatas Louis B. Flexner 《The Journal of cell biology》1968,36(2):379-390
Bitemporal intracerebral injections of puromycin in mice suppress indefinitely expression of memory of avoidance-discrimination learning. Ultrastructural studies of the entorhinal cortex of puromycin-treated mice revealed the following: (a) Abnormalities were not observed in presynaptic terminals and synaptic clefts; many postsynaptic dendrites or somas contained swollen mitochondria. (b) Dispersion of polyribosomes into single units or condensation of ribosomes into irregular aggregates with loss of "distinctiveness" was noted in a few neurons 7–27 hr after puromycin treatment. (c) Cytoplasmic aggregates of granular or amorphous material were frequently noted within otherwise normal neuronal perikarya. (d) Mitochondria in many neuronal perikarya and dendrites were swollen. Mitochondria in axons, presynaptic terminals, and glial cells were unaltered. The relationships between these lesions and the effect of puromycin on protein synthesis and memory are examined. It is suggested that the disaggregation of polysomes is too limited to explain the effect of puromycin on memory. Special emphasis is given to the swelling of mitochondria. The possible mechanisms and the significance of this lesion are discussed. 相似文献
99.
Donato Di Monte Giorgio Bellomo Hjördis Thor Pierluigi Nicotera Sten Orrenius 《Archives of biochemistry and biophysics》1984,235(2):343-350
The toxicological implications of alterations in intracellular thiol homeostasis during menadione metabolism have been investigated using freshly isolated rat hepatocytes. A strict correlation between depletion of protein sulfhydryl groups and loss of cell viability was observed. Loss of protein thiols preceded cell death, and occurred more rapidly in cells with decreased levels of reduced glutathione. Depletion of protein thiols was also associated with inhibition of Ca2+ efflux from the cells and perturbation of intracellular Ca2+ homeostasis. It is proposed that the oxidative stress induced by menadione metabolism in isolated hepatocytes results in the depletion of both soluble and protein thiols, and that the latter effect is critically associated with a perturbation of Ca2+ homeostasis and loss of cell viability. 相似文献
100.
Marta Ferraroni Wojciech R. Rypniewski Bruno Bruni Pierluigi Orioli S. Mangani 《Journal of biological inorganic chemistry》1998,3(4):411-422
The crystal structures of dithionite-reduced bovine Cu(I),Zn superoxide dismutase and of its adducts with the inorganic anions azide and thyocyanide have been determined in a C2221 crystal form obtained at pH?5.0. This crystal form is characterized by a high solvent content (72%) and by having the two Cu,ZnSOD monomers (A and B) in different crystal environments. One of them (B) is involved in few intermolecular crystal contacts so that it is in a more "solution like" environment, as indicated by average temperature factors which are about twice those of the other monomer. The differences in crystal packing affect the active site structures. While in the A monomer the Cu(I) is coordinated to all four histidine residues, in the B monomer the bridging His61 side chain is found disordered, implying partial detachment from copper. The same effect occurs in the structures of the anion complexes. The inorganic anions are found bound in the active site cavity, weakly interacting with copper at distances ranging from 2.5 to 2.8?Å. The copper site in the A subunit of the native enzyme structure displays significant electron density resembling a diatomic molecule, bound side-on at about 2.8?Å from the metal, which cannot be unambiguously interpreted. The crystallographic data suggest that the existence of the His61 bridge between copper and zinc is dominated by steric more than electronic factors and that the solution state favors the His61 detachment. These structures confirm the existence of an energetically available state for Cu(I) in Cu,ZnSOD where the histidinato bridge to zinc is maintained. This state appears to be favored by tighter crystal contacts. The binding of the anions in the active site cavity is different from that observed in the oxidized enzyme and it appears to be dominated by electrostatic interactions within the cavity. The anion binding mode observed may model the substrate interaction with the reduced enzyme during catalysis. 相似文献