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21.
22.
Tristan J. Iseli Nigel Turner Xiao-Yi Zeng Gregory J. Cooney Edward W. Kraegen Sheng Yao Yang Ye David E. James Ji-Ming Ye 《PloS one》2013,8(4)
We recently showed that bitter melon-derived triterpenoids (BMTs) activate AMPK and increase GLUT4 translocation to the plasma membrane in vitro, and improve glucose disposal in insulin resistant models in vivo. Here we interrogated the mechanism by which these novel compounds activate AMPK, a leading anti-diabetic drug target. BMTs did not activate AMPK directly in an allosteric manner as AMP or the Abbott compound (A-769662) does, nor did they activate AMPK by inhibiting cellular respiration like many commonly used anti-diabetic medications. BMTs increased AMPK activity in both L6 myotubes and LKB1-deficient HeLa cells by 20–35%. Incubation with the CaMKKβ inhibitor, STO-609, completely attenuated this effect suggesting a key role for CaMKKβ in this activation. Incubation of L6 myotubes with the calcium chelator EGTA-AM did not alter this activation suggesting that the BMT-dependent activation was Ca2+-independent. We therefore propose that CaMKKβ is a key upstream kinase for BMT-induced activation of AMPK. 相似文献
23.
Ablation of rat myenteric plexus with benzalkonium chloride has provided a model of intestinal aganglionosis, but the degenerative
responses are not well understood. We examined the effects of this detergent on neurons and glia, including expression of
c-Myc, c-Jun, JunB, and c-Fos, and on immunocytes in the guinea-pig ileum. Benzalkonium chloride (0.1%) or saline was applied
to the serosal surface of distal ileum. Tissues were analyzed 2, 3, or 7 days later and compared with cyclosporine-treated
and untreated animals. More than 90% of myenteric neurons were destroyed in ileal segments 3–7 days after benzalkonium-chloride
treatment. Glia withdrew processes from around neurons after 2 days and were mostly gone after 3 days. Neuronal c-Myc began
to disappear while c-Fos, c-Jun, and JunB were evident in some neuronal nuclei after 2 or 3 days. After 3 days, widespread
apoptosis was evident in the myenteric plexus. Populations of T cells, B cells, and macrophage-like cells in untreated and
saline-treated myenteric plexuses were substantially increased 3 and 7 days after benzalkonium-chloride treatment. Cyclosporine
delayed significant neuronal loss. We conclude that a variety of degenerative mechanisms may be active in this model, including
an immune response which may actively contribute to tissue destruction.
Received: 13 September 1996 / Accepted: 20 January 1997 相似文献
24.
Jin-Yuan Fan John C. Means Edward S. Bjes Jeffrey L. Price 《Molecular and cellular biology》2015,35(14):2414-2424
Drosophila DBT and vertebrate CKIε/δ phosphorylate the period protein (PER) to produce circadian rhythms. While the C termini of these orthologs are not conserved in amino acid sequence, they inhibit activity and become autophosphorylated in the fly and vertebrate kinases. Here, sites of C-terminal autophosphorylation were identified by mass spectrometry and analysis of DBT truncations. Mutation of 6 serines and threonines in the C terminus (DBTC/ala) prevented autophosphorylation-dependent DBT turnover and electrophoretic mobility shifts in S2 cells. Unlike the effect of autophosphorylation on CKIδ, DBT autophosphorylation in S2 cells did not reduce its in vitro activity. Moreover, overexpression of DBTC/ala did not affect circadian behavior differently from wild-type DBT (DBTWT), and neither exhibited daily electrophoretic mobility shifts, suggesting that DBT autophosphorylation is not required for clock function. While DBTWT protected S2 cells and larvae from UV-induced apoptosis and was phosphorylated and degraded by the proteasome, DBTC/ala did not protect and was not degraded. Finally, we show that the HSP-90 cochaperone spaghetti protein (SPAG) antagonizes DBT autophosphorylation in S2 cells. These results suggest that DBT autophosphorylation regulates cell death and suggest a potential mechanism by which the circadian clock might affect apoptosis. 相似文献
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A new technique has been developed for the isolation of membrane vesicles from the vitamin D-deficient and vitamin D-treated chick intestinal brush border membrane. The technique involves removal of nuclei from a low speed pellet by discontinuous sucrose gradient centrifugation. The resulting intact brush borders are then homogenized in 0.5 M Tris and the membrane fragments purified on a glycerol gradient. This preparation represents a 20-fold purification of the brush border marker sucrase. After 1α-hydroxyvitamin D3 treatment there is a significant increase in membrane phospholipid phosphorous, an alteration in the fatty acid composition of the phosphatidylcholine fraction of membrane phospholipid, and a decrease in sucrase specific activity. 相似文献
27.
Edward A. Drew 《Journal of experimental marine biology and ecology》1973,13(2):165-179
In situ measurements of the rates of photosynthesis and calcification in three species of hermatypic corals were made at Eilat, in the Gulf of Aqaba, Red Sea. Experiments were made at 5, 20 and 35 m depth under unusually poor conditions of submarine illumination for the region, and at the relatively low water temperature (21°C) for coral growth which prevails there all year. Estimates of photosynthetic rates by both the 14C and oxygen methods indicated that the 14C method does measure gross photosynthesis in these organisms even at, and below, light compensation points. Substantial rates of carbon fixation in Acropora and Millepora show that, even under bad conditions, these organisms could survive autotrophically to at least 10 m depth, as also could the massive coral Goniastrea although this had much lower photosynthetic rates under the same conditions, compensated for by a much lower respiratory rate than the other two corals.Calcification rates were variable but showed a considerable increase in light as compared with the dark in all three species, and the rates did not decrease with depth as much as might have been anticipated from the reduction in photosynthesis and ambient light energy. Photosynthetic and calcification rates were similar to those reported for similar organisms both in the Caribbean and on the Great Barrier Reef. 相似文献
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Valic Zoran; Vidruk Edward H.; Ruble Stephen B.; Buckwalter John B.; Clifford Philip S. 《Journal of applied physiology》2001,90(1):23-28
To investigate whether efferent parasympathetic fibers to the trachealsmooth muscle course through the pararecurrent nerve rather than therecurrent or the superior laryngeal nerve, we stimulated all threenerves in anesthetized dogs. We also recorded the pararecurrentnerve activity response to bronchoconstrictor stimuli and compared itwith pressure changes inside a saline-filled cuff of an endotrachealtube. Electrical stimulation (30 s, 100 Hz, 0.1 ms, 10 mA) increasedtracheal cuff pressure by 21.0 ± 3.2 and 1.3 ± 0.7 cmH2O for the pararecurrent and the recurrent laryngealnerve, respectively. Stimulation of the superior laryngeal nerveincreased tracheal cuff pressure before, but not after, sectioning ofthe ramus anastomoticus, which connects it to the pararecurrent nerve.Intravenous administration of sodium cyanide increased pararecurrentnerve activity by 208 ± 51% and tracheal cuff pressure by14.4 ± 3.5 cmH2O. Elevation of end-tidalPCO2 to 50 Torr increased pararecurrent nerveactivity by 49 ± 19% and tracheal cuff pressure by 8.4 ± 3.6 cmH2O. Further elevation to 60 Torr increasedpararecurrent nerve activity by 101 ± 33% and tracheal cuffpressure by 11.3 ± 2.9 cmH2O. These results lead usto the conclusion that parasympathetic efferent fibers reach the smoothmuscle of the canine trachea via the pararecurrent nerve. 相似文献