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991.
992.
A zinc-dependent matrix metalloproteinase (NtMMP1) found in the plasma membrane of Nicotiana tabacum cv. Bright Yellow 2 (BY-2) suspension cells is thought to be responsible for the degradation of recombinant proteins secreted
into the culture supernatant. We have characterized the proteolytic activity of NtMMP1 by expressing a recombinant derivative
lacking the C-terminal transmembrane domain in yeast. After purifying the protein by affinity chromatography, its autocatalytic
activity was analyzed using monoclonal antibodies raised against its N-terminal and C-terminal portions. Both the unprocessed
and processed forms of NtMMP1 displayed caseinolytic activity and N-terminal sequencing identified an autocatalytic cleavage
site within the sequence motif HFSFFP, which is similar to the corresponding sequences of the human matrix metalloproteinases
stromelysin-1 (MMP-3) and stromelysin-2 (MMP-10). Unlike all other matrix metalloproteinases investigated so far, NtMMP1 contains
a disulfide bond within its propeptide thus rendering the proenzyme catalytically active. Kinetic analysis of NtMMP1 with
a synthetic substrate revealed a K
m of 10.55 ± 0.9 μM, a k
cat of 0.6 ± 0.01 s−1 and maximum activity at pH 7.5. We found that NtMMP1 degrades Desmodus rotundus salivary plasminogen activator alpha 1 (DSPAα1), a biopharmaceutical protein, that has proven difficult to produce in tobacco
BY-2 cells. This provides a likely explanation for the frequent instability of secreted recombinant biopharmaceuticals produced
in plant suspension cell cultures. Our data suggest new avenues that can be explored to improve the production of pharmaceutical
proteins in plants and plant cells. 相似文献
993.
Alpana Sharma Medha Rajappa Abhigyan Satyam Manoj Sharma 《Molecular and cellular biochemistry》2010,333(1-2):65-72
The present study was designed to investigate the effects of benzyloxicarbonyl-l-phenylalanyl-alanine-fluoromethylketone (Z-FA.FMK), an inhibitor of cathepsin B on lung injury that occurs concurrently with liver injury induced by d-galactosamine/tumor necrosis factor-alpha (d-GalN/TNF-α). Four groups of BALB/c male mice were treated as follows: Group 1—mice receiving intravenous (iv) injections of physiological saline; Group 2—administered with 8 mg/kg Z-FA.FMK by iv injection; Group 3—mice treated with 700 mg/kg d-GalN and 15 μg/kg TNF-α by sequential intraperitoneal (ip) injection; Group 4—treated with 700 mg/kg d-GalN and 15 μg/kg TNF-α by sequential ip injection 1 h after administration with 8 mg/kg Z-FA.FMK. Mice from Groups 3 and 4 were sacrificed 4 h after d-GalN/TNF-α injections. The mice treated with d-GalN/TNF-α showed lung damage; increased TNF receptor-associated factor immunoreactivity, lipid peroxidation, protein carbonyl content, and lactate dehydrogenase activity; decreased catalase, superoxide dismutase, and paraoxonase activities. Treatment with Z-FA.FMK resulted in an improvement of these alterations in d-GalN/TNF-α-administered mice. The apoptotic index of type-II pneumocytes was the almost same in the four study groups, but pneumocytes labeled with proliferating cell nuclear antigen antibody was more numerous in Group 4 mice. Our results show that d-GalN/TNF-α results in lung damage without induction of apoptosis. Treatment with Z-FA.FMK stimulates proliferation of type-II pneumocytes and improves degenerative alterations in injured lung occurred with liver injury induced by d-GalN/TNF-α. 相似文献
994.
Ya Fatou Njie-Mbye Odelia Y. N. Bongmba Chinwe C. Onyema Abhishek Chitnis Madhura Kulkarni Catherine A. Opere Angela M. LeDay Sunny E. Ohia 《Neurochemical research》2010,35(3):487-494
Hydrogen sulfide (H2S) has been reported to exert pharmacological effects on neural and non-neural tissues from several mammalian species. In
the present study, we examined the role of the intracellular messenger, cyclic AMP in retinal response to H2S donors, sodium hydrosulfide (NaHS) and sodium sulfide (Na2S) in cows and pigs. Isolated bovine and porcine neural retinae were incubated in oxygenated Krebs buffer solution prior to
exposure to varying concentrations of NaHS, Na2S or the diterpene activator of adenylate cyclase, forskolin. After incubation at different time intervals, tissue homogenates
were prepared for cyclic AMP assay using a well established methodology. In isolated bovine and porcine retinae, the combination
of both phosphodiesterase inhibitor, IBMX (2 mM) and forskolin (10 μM) produced a synergistic increase (P < 0.001) in cyclic AMP concentrations over basal levels. NaHS (10 nM–100 μM) produced a time-dependent increase in cyclic
AMP concentrations over basal levels which reached a maximum at 20 min in both bovine and porcine retinae. At this time point,
both NaHS and Na2S (10 nM–100 μM) caused a significant (P < 0.05) dose-dependent increase in cyclic AMP levels in bovine and porcine retinae. For instance, NaHS (100 nM) elicited
a four-fold and three-fold increase in cyclic AMP concentrations in bovine and porcine retinae respectively whilst higher
concentrations of Na2S (100 μM) produced a much lesser effect in both species. In bovine and porcine retinae, the effects caused by forskolin (10 μM)
on cyclic AMP production were not potentiated by addition of low or high concentrations of both NaHS and Na2S. We conclude that H2S donors can increase cyclic AMP production in isolated neural retinae from cows and pigs. Bovine retina appears to be more
sensitive to the stimulatory effect of H2S donors on cyclic nucleotide production than its porcine counterpart indicating that species differences exist in the magnitude
of this response. Furthermore, effects produced by forskolin on cyclic AMP formation were not additive with those elicited
by H2S donors suggesting that these agents may share a common mechanism in their action on the adenylyl cyclase pathway. 相似文献
995.
Sashidhara KV Kumar A Kumar M Srivastava A Puri A 《Bioorganic & medicinal chemistry letters》2010,20(22):6504-6507
A series of novel coumarin bisindole heterocycles were synthesized following an uncommon method and evaluated for their antihyperlipidemic activity in hyperlipidemic hamster model. Among 12 compounds tested, the compound 5e showed potent antihyperlipidemic activity and was found to decrease the plasma triglyceride levels (TG) by 55%, total cholesterol (TC) by 20%, accompanied by an increase in HDL-C/TC ratio by 42% in hyperlipidemic rats to a greater degree than some of the reference statins. 相似文献
996.
Harmeet S. Sandhu Sameer Sapra Mukesh Gupta Kunal Nepali Raju Gautam Sunil Yadav Raj Kumar Sanjay M. Jachak Manoj Chugh Manish K. Gupta Om P. Suri K.L. Dhar 《Bioorganic & medicinal chemistry》2010,18(15):5626-5633
A series of arylidene analogues of Meldrum’s acid were synthesized and evaluated for in vitro antimalarial and antioxidant activities for the first time. The influence of various physico-chemical parameters such as dielectric constant (ε), donor number (DN), acceptor number (AN), hydrogen bond donor (HBD), hydrogen bond acceptor (HBA), and solubilizing power of the solvents on Meldrum’s acid anion generation and thus on promoting the Knoevenagel condensation of Meldrum’s acid with aryl aldehydes has been discussed. Five compounds 9l, 9m, 9n, 9r, and 9s were found to be most active against Plasmodium falciparum with IC50 values in the range of 9.68–16.11 μM. Compound 9l exhibited the most potent antimalarial activity (IC50 9.68 μM). The compounds were also found to possess antioxidant activity when tested against DPPH and ABTS free radicals. 相似文献
997.
Walter P. Suza Carlos A. Avila Kelly Carruthers Shashank Kulkarni Fiona L. Goggin Argelia Lorence 《Plant Physiology and Biochemistry》2010,48(5):337-350
Vitamin C (ascorbate, AsA) is the most abundant water-soluble antioxidant in plants. Ascorbate provides the first line of defense against damaging reactive oxygen species (ROS), and helps protect plant cells from many factors that induce oxidative stress, including wounding, ozone, high salinity, and pathogen attack. Plant defenses against these stresses are also dependent upon jasmonates (JAs), a class of plant hormones that promote ROS accumulation. Here, we review evidence showing that wounding and JAs influence AsA accumulation in various plant species, and we report new data from Arabidopsis and tomato testing the influence of JAs on AsA levels in wounded and unwounded plants. In both species, certain mutations that impair JA metabolism and signaling influence foliar AsA levels, suggesting that endogenous JAs may regulate steady-state AsA. However, the impact of wounding on AsA accumulation was similar in JA mutants and wild type controls, indicating that this wound response does not require JAs. Our findings also indicate that the effects of wounding and JAs on AsA accumulation differ between species; these factors both enhanced AsA accumulation in Arabidopsis, but depressed AsA levels in tomato. These results underscore the importance of obtaining data from more than one model species, and demonstrate the complexity of AsA regulation. 相似文献
998.
999.
Abhinav Choubey Khyati Girdhar Aditya K. Kar Shaivya Kushwaha Manoj Kumar Yadav Debabrata Ghosh Prosenjit Mondal 《The Journal of biological chemistry》2020,295(48):16359
The incidence of diabetes, obesity, and metabolic diseases has reached an epidemic status worldwide. Insulin resistance is a common link in the development of these conditions, and hyperinsulinemia is a central hallmark of peripheral insulin resistance. However, how hyperinsulinemia leads to systemic insulin resistance is less clear. We now provide evidence that hyperinsulinemia promotes the release of soluble pro-inflammatory mediators from macrophages that lead to systemic insulin resistance. Our observations suggest that hyperinsulinemia induces sirtuin1 (SIRT1) repression and stimulates NF-κB p65 nuclear translocation and transactivation of NF-κB to promote the extracellular release of pro-inflammatory mediators. We further showed that low-dose naltrexone (LDN) abrogates hyperinsulinemia-mediated SIRT1 repression and prevents NF-κB p65 nuclear translocation. This, in turn, attenuates the hyperinsulinemia-induced release of pro-inflammatory cytokines and reinstates insulin sensitivity both in in vitro and in vivo diet-induced hyperinsulinemic mouse model. Notably, our data indicate that Sirt1 knockdown or inhibition blunts the anti-inflammatory properties of LDN in vitro. Using numerous complementary in silico and in vitro experimental approaches, we demonstrated that LDN can bind to SIRT1 and increase its deacetylase activity. Together, these data support a critical role of SIRT1 in inflammation and insulin resistance in hyperinsulinemia. LDN improves hyperinsulinemia-induced insulin resistance by reorienting macrophages toward anti-inflammation. Thus, LDN treatment may provide a novel therapeutic approach against hyperinsulinemia-associated insulin resistance. 相似文献
1000.
Sheelavanta M. Shivaraj Sanskriti Vats Javaid A. Bhat Priyanka Dhakte Vinod Goyal Praveen Khatri Surbhi Kumawat Akshay Singh Manoj Prasad Humira Sonah Tilak R. Sharma Rupesh Deshmukh 《Physiologia plantarum》2020,168(2):437-455
Gases such as ethylene, hydrogen peroxide (H2O2), nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) have been recognized as vital signaling molecules in plants and animals. Of these gasotransmitters, NO and H2S have recently gained momentum mainly because of their involvement in numerous cellular processes. It is therefore important to study their various attributes including their biosynthetic and signaling pathways. The present review provides an insight into various routes for the biosynthesis of NO and H2S as well as their signaling role in plant cells under different conditions, more particularly under heavy metal stress. Their beneficial roles in the plant's protection against abiotic and biotic stresses as well as their adverse effects have been addressed. This review describes how H2S and NO, being very small-sized molecules, can quickly pass through the cell membranes and trigger a multitude of responses to various factors, notably to various stress conditions such as drought, heat, osmotic, heavy metal and multiple biotic stresses. The versatile interactions between H2S and NO involved in the different molecular pathways have been discussed. In addition to the signaling role of H2S and NO, their direct role in posttranslational modifications is also considered. The information provided here will be helpful to better understand the multifaceted roles of H2S and NO in plants, particularly under stress conditions. 相似文献