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21.
Glucose phosphorylation and mitochondrial binding are required for the protective effects of hexokinases I and II 总被引:3,自引:0,他引:3
Alterations in glucose metabolism have been demonstrated for diverse disorders ranging from heart disease to cancer. The first step in glucose metabolism is carried out by the hexokinase (HK) family of enzymes. HKI and II can bind to mitochondria through their N-terminal hydrophobic regions, and their overexpression in tissue culture protects against cell death. In order to determine the relative contributions of mitochondrial binding and glucose-phosphorylating activities of HKs to their overall protective effects, we expressed full-length HKI and HKII, their truncated proteins lacking the mitochondrial binding domains, and catalytically inactive proteins in tissue culture. The overexpression of full-length proteins resulted in protection against cell death, decreased levels of reactive oxygen species, and possibly inhibited mitochondrial permeability transition in response to H2O2. However, the truncated and mutant proteins exerted only partial effects. Similar results were obtained with primary neonatal rat cardiomyocytes. The HK proteins also resulted in an increase in the phosphorylation of voltage-dependent anion channel (VDAC) through a protein kinase C (PKC)-dependent pathway. These results suggest that both glucose phosphorylation and mitochondrial binding contribute to the protective effects of HKI and HKII, possibly through VDAC phosphorylation by PKC. 相似文献
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23.
Adnan A. Bekhit Eskedar T. Lodebo Ariaya Hymete Hanan M. Ragab Salma A. Bekhit Kikuko Amagase Afnan Batubara Mohammed A. S. Abourehab Alaa El-Din A. Bekhit Tamer M. Ibrahim 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):2320
Promising inhibitory activities of the parasite multiplication were obtained upon evaluation of in vivo antimalarial activities of new pyrazolylpyrazoline derivatives against Plasmodium berghei infected mice. Further evaluation of 5b and 6a against chloroquine-resistant strain (RKL9) of P. falciparum showed higher potency than chloroquine. In vitro antileishmanial activity testing against Leishmania aethiopica promastigote and amastigote forms indicated that 5b, 6a and 7b possessed promising activity compared to miltefosine and amphotericin B deoxycholate. Moreover, antileishmanial activity reversal of the active compounds via folic and folinic acids showed comparable results to the positive control trimethoprim, indicating an antifolate mechanism via targeting leishmanial DHFR and PTR1. The compounds were non-toxic at 125, 250 and 500 mg/kg. In addition, docking of the most active compound against putative malarial target Pf-DHFR-TS and leishmanial PTR1 rationalised the observed activities. Molecular dynamics simulations confirmed a stable and high potential binding of 7a against leishmanial PTR1. 相似文献
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25.
Das SK Narasimha Rao Krovvidi VL Jagadheshan H Iqbal J 《Bioorganic & medicinal chemistry letters》2002,12(24):3579-3581
cis-4-Amino-L-proline derivatives 1 and 2 derived from quinazolinone and pyrazolo pyrimidone respectively were designed as novel lipid lowering agents. A preliminary in vivo screening indicates that 1b and 2a have moderate triglyceride lowering activity. 相似文献
26.
We have studied the effect of 2,2,2-trifluoroethanol (TFE), an α-helix inducer, versus methyl cyanide (MeCN), a β-sheet inducer,
on acid-denatured human serum albumin (HSA) using far-UV circular dichroism, intrinsic fluorescence, 1-anilino-8-naphthalene
sulfonate binding, and acrylamide quenching studies. Interestingly, at pH 2.0, where the recovery and resolution of the protein
in reverse phase chromatography is high, its secondary structure remains unchanged even in the presence of very high concentration
(76% v/v) of MeCN. Gain of 23 and 34% α-helicity was observed in the presence of 20 and 50% TFE, respectively. At pH 7.3,
HSA aggregates in the presence of 40% MeCN, but it remains soluble up to 75% MeCN at pH 2.0. The results seem to be important
for HSA isolation and purification. 相似文献
27.
Asma Haque Tayyaba Shaheen Tahsin Gulzar Mahmood ur Rahman Fatima Jalal Summera Sattar Beenish Ehsan Zafar Iqbal Muhammad Younas 《Bioinformation》2014,10(6):371-377
Wheat is a vital dietary component for human health and widely consumed in the world. Wheat rusts are dangerous pathogens
and contribute serious threat to its production. In present study, PCR-Based DNA Markers were employed to check the rust
resistance genes among 20 wheat genotypes and 22 markers were amplified. NTSYS-pc 2.2 was used to calculate genetic diversity
and Nei and Li''s coefficients ranged from 0.55 to 0.95. Cluster analysis was obtained using UPGMA (Unweighted Pair Group
Method of Arithmetic Average) algorithm. Maximum no. of genes (23) was amplified from TW-760010 genotype whereas
minimum no of genes (14) were amplified from TW-76005 genotype. The data gained from present study open up new ways to
produce new varieties by breeding rust resistant germplasm to avoid the economic and food loss and varieties with improved
characteristics. 相似文献
28.
Apicomplexans, including the pathogens Plasmodium and Toxoplasma, carry a nonphotosynthetic plastid of secondary endosymbiotic origin called the apicoplast. The P. falciparum apicoplast contains a 35 kb, circular DNA genome with limited coding capacity that lacks genes encoding proteins for DNA organization and replication. We report identification of a nuclear-encoded bacterial histone-like protein (PfHU) involved in DNA compaction in the apicoplast. PfHU is associated with apicoplast DNA and is expressed throughout the parasite's intra-erythocytic cycle. The protein binds DNA in a sequence nonspecific manner with a minimum binding site length of ~27 bp and a Kd of ~63 nM and displays a preference for supercoiled DNA. PfHU is capable of condensing Escherichia coli nucleoids in vivo indicating its role in DNA compaction. The unique 42 aa C-terminal extension of PfHU influences its DNA condensation properties. In contrast to bacterial HUs that bend DNA, PfHU promotes concatenation of linear DNA and inhibits DNA circularization. Atomic Force Microscopic study of PfHU–DNA complexes shows protein concentration-dependent DNA stiffening, intermolecular bundling and formation of DNA bridges followed by assembly of condensed DNA networks. Our results provide the first functional characterization of an apicomplexan HU protein and provide additional evidence for red algal ancestry of the apicoplast. 相似文献
29.
Novel cyclization of 4-(substituted-phenylsulfonamido)butanoic acids to their corresponding 1-[(substituted-phenyl)sulfonyl]pyrrolidin-2-ones was successfully achieved by using polyphosphate ester (PPE). The reaction time was considerably reduced with corresponding increase in the yields, when polyphosphate ester (PPE) was used in combination with 4-(N,N-dimethylamino)pyridine (DMAP). All the synthesized compounds were screened for their antimicrobial activity. Minimum Inhibitory Concentration (MIC) values of synthesized compounds were also determined, and were found to be in the range of 0.09-1.0 mg. 相似文献
30.
Shoots and roots ofBacopa monniera (L.) Wettst. have been regenerated from nodal segments on MS medium containing combinations of NAA and BAP. The cultures
showed 100% regeneration on MS (sucrose 2%) medium added with NAA (0.2 mg L-1), BAP (0.5 mg L-1) and glutamine (50 mg L-1). Supplemented with aluminium chloride (up to 400 μM), this medium could ensure successful survival of regenerants. AH the
regenerants, maintained on AlCl3-supplemented medium for the last three years, failed to grow when transferred to AlCl3-free media. Aluminium stress also induced synthesis of proline and proteins. The rate of photosynthesis decreased at increased
aluminium concentrations. 相似文献