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101.
Tosha T Yoshioka S Takahashi S Ishimori K Shimada H Morishima I 《The Journal of biological chemistry》2003,278(41):39809-39821
We investigated putidaredoxin-induced structural changes in carbonmonoxy P450cam by using NMR spectroscopy. The resonance from the beta-proton of the axial cysteine was upfield shifted by 0.12 ppm upon the putidaredoxin binding, indicating that the axial cysteine approaches to the heme-iron by about 0.1 A. The approach of the axial cysteine to the heme-iron would enhance the electronic donation from the axial thiolate to the heme-iron, resulting in the enhanced heterolysis of the dioxygen bond. In addition to the structural perturbation on the axial ligand, the structural changes in the substrate and ligand binding site were observed. The resonances from the 5-exo- and 9-methyl-protons of d-camphor, which were newly identified in this study, were upfield shifted by 1.28 and 0.20 ppm, respectively, implying that d-camphor moves to the heme-iron by 0.15-0.7 A. Based on the radical rebound mechanism, the approach of d-camphor to the heme-iron could promote the oxygen transfer reaction. On the other hand, the downfield shift of the resonance from the gamma-methyl group of Thr-252 reflects the movement of the side chain away from the heme-iron by approximately 0.25 A. Because Thr-252 regulates the heterolysis of the dioxygen bond, the positional rearrangement of Thr-252 might assist the scission of the dioxygen bond. We, therefore, conclude that putidaredoxin induces the specific heme environmental changes of P450cam, which would facilitate the oxygen activation and the oxygen transfer reaction. 相似文献
102.
In Memanbetsu town, Hokkaido island, Japan, a high frequency of natural triploid loaches Misgurnus anguillicaudatus (7.4% on average) was detected by flow cytometry for relative DNA content. Among sympatric diploid females (n=6) from a single population, we found two unique females that laid unreduced diploid eggs. They gave normal diploid progeny even after induction of gynogenesis with genetically inert UV-irradiated sperm. When fertilized with normal loach sperm, some unreduced eggs developed into triploids, but the rest into diploids. Hybridization using goldfish Carassius auratus sperm gave both normal diploid loaches and inviable allotriploid hybrids possessing the diploid loach genome and the haploid goldfish genome. Microsatellite genotyping and DNA fingerprinting demonstrated that the diploid progeny developing from the unreduced eggs were genetically identical to the mother, while the triploids had some of the paternal DNA. These results indicate that the diploid eggs reproduced unisexually as a diploid clone and in other cases developed into triploids after accidental incorporation of sperm nucleus. The presence of at least one clonal line in this area was shown by the identical DNA fingerprint detected in five out of 17 diploid loaches examined. 相似文献
103.
An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12 总被引:32,自引:0,他引:32
Morishima N Nakanishi K Takenouchi H Shibata T Yasuhiko Y 《The Journal of biological chemistry》2002,277(37):34287-34294
Activation of caspase-12 from procaspase-12 is specifically induced by insult to the endoplasmic reticulum (ER) (Nakagawa, T., Zhu, H., Morishima, N., Li, E., Xu, J., Yankner, B. A., and Yuan, J. (2000) Nature 403, 98-103), yet the functional consequences of caspase-12 activation have been unclear. We have shown that recombinant caspase-12 specifically cleaves and activates procaspase-9 in cytosolic extracts. The activated caspase-9 catalyzes cleavage of procaspase-3, which is inhibitable by a caspase-9-specific inhibitor. Although cytochrome c released from mitochondria has been believed to be required for caspase-9 activation during apoptosis (Zou, H., Henzel, W. J., Liu, X., Lutschg, A., and Wang, X. (1997) Cell 90, 405-413, Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., Alnemri, E. S., and Wang, X. (1997) Cell 91, 479-489), caspase-9 as well as caspase-12 and -3 are activated in cytochrome c-free cytosols in murine myoblast cells under ER stress. These results suggest that caspase-12 can activate caspase-9 without involvement of cytochrome c. To examine the role of caspase-12 in the activation of downstream caspases, we used a caspase-12-binding protein, which we identified in a yeast two-hybrid screen, for regulation of caspase-12 activation. The binding protein protects procaspase-12 from processing in vitro. Stable expression of the binding protein renders procaspase-12 insensitive to ER stress, thereby suppressing apoptosis and the activation of caspase-9 and -3. These data suggest that procaspase-9 is a substrate of caspase-12 and that ER stress triggers a specific cascade involving caspase-12, -9, and -3 in a cytochrome c-independent manner. 相似文献
104.
Sato H Sakoh H Hashihayata T Imamura H Ohtake N Shimizu A Sugimoto Y Sakuraba S Bamba-Nagano R Yamada K Hashizume T Morishima H 《Bioorganic & medicinal chemistry》2002,10(5):1595-1610
Structure--activity relationship studies of 1beta-methyl-2-[(3S,5R)-5-(4-aminomethylphenyl)pyrrolidin-3-ylthio]carbapenems, especially those pertaining to the relationship between antibacterial activity and side-chain structure were conducted. These studies suggested that the trans-(3S,5R)-5-phenylpyrrolidin-3-ylthio side-chain and the aminomethyl group at the 4-position of the phenyl ring play a key role in enhancing the antibacterial activity against the MRSA and Pseudomonas aeruginosa strains. In particular, the basicity of a substituent at the 4-position of the phenyl ring were shown to greatly contribute to the antibacterial activity against MRSA and methicillin-resistant Staphyloccocus epidermidis strains. In contrast, the amidine group was shown to lead to potent antibacterial activity against P. aeruginosa strains comparable to that of imipenem, however, a good correlation between the basicity of the 4-substituent and antipseudomonal activity was not observed. In conclusion, the 4-aminomethyl or methylaminomethyl group on the phenyl ring was the best substituent for antipseudomonal activity. 相似文献
105.
To characterize the protein-protein interaction during electron transfer, we used Zn-substituted cytochrome c (ZnCytc) as a model of ferrous Cytc and determined the volume change, DeltaV(d)(Zn), for the dissociation of its complex with ferric cytochrome b(5) (Cytb(5)) by the pressure dependence of its photoinduced electron-transfer kinetics. Under ambient pressure, the dissociation constant, K(d)(Zn), of the ZnCytc/Cytb(5) complex was dependent on the buffer concentration, 1.5 and 12 microM in 2 and 10 mM Tris-HCl, pH 7.4, respectively, which was consistent with formation of salt bridges in its complexation. The dissociation of one salt bridge is usually associated with large volume changes of -10 to -30 cm(3) mol(-1), while pressure dependence of K(d)(Zn) resulted in smaller value of DeltaV(d)(Zn), -8.5 cm(3) mol(-1). Therefore, the interaction between ZnCytc and Cytb(5) cannot be explained only by salt bridge interaction, and the partial cancellation by the positive volume change due to the additional hydrophobic interaction is a plausible explanation for the observed DeltaV(d)(Zn). In addition, DeltaV(d)(Zn) of -8.5 cm(3) mol(-1) was considerably smaller than the previously reported volume change, DeltaV(d)(Fe), of -122 cm(3) mol(-1) in the ferric Cytc/Cytb(5) complex dissociation [Rodgers and Sligar (1991) J. Mol. Biol. 221, 1453-1460]. ZnCytc used here has been assumed to be a reliable model of ferrous Cytc, and thus the discrepancy between our present DeltaV(d)(Zn) and the previous DeltaV(d)(Fe) is discussed on the basis of the protein docking dependent on the oxidation states of heme iron in Cytc. 相似文献
106.
107.
Protective effects of carvedilol against doxorubicin-induced cardiomyopathy in rats. 总被引:6,自引:0,他引:6
Carvedilol (CAR) is a vasodilating beta-blocker which also has antioxidant properties. CAR produces dose-related reduction in mortality in patients with congestive heart failure. In the present study, we tested the hypothesis that CAR protects against doxorubicin (DOX)-induced cardiomyopathy in rats. Sprague-Dawley rats were treated with DOX, CAR, CAR+DOX, or atenolol (ATN)+DOX. DOX (cumulative dose, 15 mg/kg) was administered intraperitoneally, and CAR (30 mg/kg daily) or ATN (150 mg/kg daily) was administered orally. Three weeks after the completion of these treatments, cardiac performance and myocardial lipid peroxidation were assessed. Mortality was observed in the DOX (25%) and ATN+DOX (12.5%) groups. Compared with control rats, DOX significantly decreased systolic blood pressure (104+/-4 vs. 120+/-4 mmHg, P<0.05) and left ventricular fractional shortening (38.8+/-3.1 vs. 55.4+/-1.3%, P<0.01), and resulted in a significant accumulation of ascites (14.4+/-4.9 vs. 0 ml, P<0.01). CAR significantly prevented the cardiomyopathic changes caused by DOX, while ATN did not. The myocardial thiobarbituric acid reactive substances (TBARS) content was significantly higher in DOX-treated rats than in control rats (80.4+/-7.1 vs. 51.5+/-1.2 nmol/g heart, p<0.01). CAR prevented the increase in TBARS content (48.8+/-3.0 nmol/g heart, P<0.01 vs. DOX group), whereas ATN had no significant effect (74.3+/-5.2 nmol/g heart). CAR also significantly prevented the increase in both myocardial and plasma cholesterol concentrations caused by DOX. These data indicate that CAR protects against DOX-induced cardiomyopathy and that this effect may be attributed to the antioxidant and lipid-lowering properties of CAR, not to its beta-blocking property. 相似文献
108.
Fumiki Yoshizako Teruo Ueno Isao Morishima Tetsunobu Karakawa Satoshi Sugiura Takaaki Araki 《Bioscience, biotechnology, and biochemistry》2013,77(3):877-879
Two principal toxins of diarrhetic shellfish poisoning, okadaic acid and dinophysistoxin-1, were esterified with 9-anthryldiazomethane in methanol. After cleaning with a Sep-pak silica cartridge column, the fluorescent esters were analyzed on a Develosil ODS column with MeCN- MeOH-H20 (8:1:1). The fluorescence intensities of both toxin derivatives measured at an excitation of 365 nm and an emission of 412 nm showed good linearity in the range 1 ~ 80ng. 相似文献
109.
110.