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21.
Inducible NOS inhibition reverses tobacco-smoke-induced emphysema and pulmonary hypertension in mice
Seimetz M Parajuli N Pichl A Veit F Kwapiszewska G Weisel FC Milger K Egemnazarov B Turowska A Fuchs B Nikam S Roth M Sydykov A Medebach T Klepetko W Jaksch P Dumitrascu R Garn H Voswinckel R Kostin S Seeger W Schermuly RT Grimminger F Ghofrani HA Weissmann N 《Cell》2011,147(2):293-305
Chronic obstructive pulmonary disease (COPD) is one of the most common causes of death worldwide. We report in an emphysema model of mice chronically exposed to tobacco smoke that pulmonary vascular dysfunction, vascular remodeling, and pulmonary hypertension (PH) precede development of alveolar destruction. We provide evidence for a causative role of inducible nitric oxide synthase (iNOS) and peroxynitrite in this context. Mice lacking iNOS were protected against emphysema and PH. Treatment of wild-type mice with the iNOS inhibitor N(6)-(1-iminoethyl)-L-lysine (L-NIL) prevented structural and functional alterations of both the lung vasculature and alveoli and also reversed established disease. In chimeric mice lacking iNOS in bone marrow (BM)-derived cells, PH was dependent on iNOS from BM-derived cells, whereas emphysema development was dependent on iNOS from non-BM-derived cells. Similar regulatory and structural alterations as seen in mouse lungs were found in lung tissue from humans with end-stage COPD. 相似文献
22.
Vinayak H. Lokhande Tukaram D. Nikam Vikas Y. Patade Mahendra L. Ahire P. Suprasanna 《Plant Cell, Tissue and Organ Culture》2011,104(1):41-49
The effect of optimal and supra-optimal concentrations (0, 200, 400 or 600 mM) of NaCl on the growth, osmotic adjustment and
antioxidant enzyme defence was studied in the in vitro cultures of Sesuvium portulacastrum. A significant increase in growth, tissue water content (TWC) and fresh to dry weight ratio (FW/DW) was observed in the shoots
exposed to 200 mM salt. Minimum damage to the membrane in terms of low relative electrolytic leakage (REL) and malondialdehyde
(MDA) content and better osmotic adjustment at 200 mM salt stress was coupled with the higher accumulation of sodium ions
and total soluble sugars as against low proline and glycine betaine contents. A fine tuning of antioxidant enzyme activities
(superoxide dismutase, catalase and ascorbate peroxidase) was also found to be responsible for the optimum growth of shoots.
In contrast, sub-optimal (0 mM) and supra-optimal concentrations (400–600 mM) of NaCl significantly affected the growth, water
status and increased the REL as well as MDA content of the shoots due to the accumulation of toxic concentrations of saline
ions. The highest accumulation of proline and glycine betaine in addition to antioxidant enzyme activities exhibited higher
osmotic adjustment and survival of the shoots under sub- or supra-optimal concentrations of NaCl as a penalty to reduced growth. 相似文献
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24.
Jitendra Gopichand Patil Mahendra Laxman Ahire Kirti Manik Nitnaware Sayantan Panda Vijay P. Bhatt Polavarapu B. Kavi Kishor Tukaram Dayaram Nikam 《Applied microbiology and biotechnology》2013,97(6):2379-2393
Digitalis purpurea L. (Scrophulariaceae; Foxglove) is a source of cardiotonic glycosides such as digitoxin and digoxin which are commercially applied in the treatment to strengthen cardiac diffusion and to regulate heart rhythm. This investigation deals with in vitro propagation and elicited production of cardiotonic glycosides digitoxin and digoxin in shoot cultures of D. purpurea L. In vitro germinated seedlings were used as a primary source of explants. Multiple shoot formation was achieved for three explant types (nodal, internodal, and leaf) cultured on Murashige and Skoog (MS) medium with several treatments of cytokinins (6-benzyladenine—BA; kinetin—Kin; and thidiazuron—TDZ) and auxins (indole-3-acetic acid—IAA; α-naphthaleneacetic acid—NAA; and 2,4-dichlorophenoxy acetic acid—2,4-D). Maximum multiple shoots (12.7?±?0.6) were produced from nodal explants on MS?+?7.5 μM BA. Shoots were rooted in vitro on MS containing 15 μM IAA. Rooted plantlets were successfully acclimatized. To further maintain the multiple shoot induction, mother tissue was cut into four equal parts and repeatedly sub-cultured on fresh shoot induction liquid medium after each harvest. On adaptation of this strategy, an average of 18 shoots per explant could be produced. This strategy was applied for the production of biomass and glycosides digitoxin and digoxin in shoot cultures on MS medium supplemented with 7.5 μM BA and several treatments with plant growth regulators, incubation period, abiotic (salicylic acid, mannitol, sorbitol, PEG-6000, NaCl, and KCl), biotic (Aspergillus niger, Helminthosporium sp., Alternaria sp., chitin, and yeast extract) elicitors, and precursors (progesterone, cholesterol, and squalene). The treatment of KCl, mycelial mass of Helminthosporium sp., and progesterone were highly effective for the production of cardenolides. In the presence of progesterone (200 to 300 mg/l), digitoxin and digoxin accumulation was enhanced by 9.1- and 11.9-folds respectively. 相似文献
25.
Vinayak Haribhau Lokhande Tukaram Dayaram Nikam Suprasanna Penna 《Plant Cell, Tissue and Organ Culture》2010,102(1):17-25
In vitro-grown cells of Sesuvium portulacastrum L., an important ‘salt accumulator’ mangrove associate, were incubated on a medium containing different levels of salt, including
0, 100, 200, or 400 mM NaCl, in order to evaluate biochemical, physiological, and growth responses. A significant decrease
in callus growth, water status, and cell membrane damage was observed under salt stress. Osmotic adjustment was revealed by
the accumulation of inorganic ions, such as sodium (Na+), and organic osmolytes (proline, glycine betaine, and total soluble sugars) in NaCl-treated calli compared to control. However,
accretion of osmolytes and inorganic ions did not support growth of calli under NaCl stress conditions. The observed reduced
growth rate in calli subjected to stress, up to 200 mM NaCl, was coupled with lower catalase and ascorbate peroxidase activities
and with a significantly higher superoxide dismutase activity. These findings suggested that S. portulacastrum cell cultures exhibited higher osmotic adjustment to salt stress. 相似文献
26.
Callus induction and in vitro plantlet regeneration systems for safflower (Carthamus tinctorius L.) cv. Bhima using root,
hypocotyl, cotyledon and leaf explants were optimized by studying the influence on organogenesis of seedling age, media factors,
growth regulators and excision orientation. Supplementation of the medium with an auxin: cytokinin ratio < 1 enhanced the
growth rate of callus cultures; however, for 2,4-D the ratio was > 1.34–11.41 μM concentrations of growth regulators (IAA,
NAA, BA and Kinetin) in the medium were found effective for callus induction and regeneration in all explants. The calli could
be maintained over 32 months. BA (4.43 μM) combined with casein hydrolysate (10 mg l-1) yielded the highest rate of shoot
production on hypocotyl (3–6) and cotyledon (5–7) explants and cotyledonary derived callus (4–8). More shoots were produced
on explants cut from the most basal region of cotyledons from 5 to 7-day-old seedlings than from older seedlings or more distal
cut sites. Apolar placement of explants, inhibited shoot regeneration. The shoot regeneration potential remained upto 7 months
in calli developed on NAA + BA. Of three media tested, MS was superior to SH-M and B5. Rooting of shoots was not efficient;
42% of the shoots were rooted on MS medium containing sucrose (7–8%) + IAA (2.8–5.7 μM). Capitula induction was observed in
both callus mediated shoots on cotyledons and shoots on rooting medium with sucrose, IAA, NAA and IBA. Well developed plantlets
were transferred to the field with a 34% success rate.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
27.
In an attempt to define pharmacophoric differences between 5-HT1, 5-HT1A and 5-HT2 recognition sites, a number of rigid analogs were studied and compared to analogous free chain tryptamines. Racemic partial ergolines RU 27849 and RU 28306 showed reduced potency at all 5-HT1 sites, but were at least equipotent to analogous tryptamines at the 5-HT2 site. A nonergoline-like constrained analog of tryptamine was similar in potency to RU 27849 at all 5-HT1 sites, but showed a 4-fold enhancement in potency over RU 27849 and tryptamine at the 5-HT2 site. At all 3 sites, 3-(tetrahydropyridyl) indoles (unless substituted at the indole 2-position) were the most potent rigid analogs studied and represent the most promising class for the development of selective compounds. 相似文献
28.
L Y Hu T R Ryder S S Nikam E Millerman B G Szoke M F Rafferty 《Bioorganic & medicinal chemistry letters》1999,9(8):1121-1126
Selective N-type Voltage Activated Calcium Channel (VACC) blockers have shown utility in several models of stroke and pain. In the process of searching for small molecules as N-type calcium channel blockers, we have identified a series of N,N-dialkylpeptidylamines (e.g., PD 175069) with potent functional activity at N-type VACC. Further modification of the leucine moiety of PD 175069 with a cyclized ring structure provides a series of novel molecules. Syntheses and pharmacological evaluation of the series are presented. 相似文献
29.
Vinayak H. Lokhande Ashish K. Srivastava Sudhakar Srivastava Tukaram D. Nikam Penna Suprasanna 《Plant Growth Regulation》2011,65(2):287-298
The present work addresses the importance of antioxidant, redox and energetic parameters in regulating salt-tolerance in Sesuvium portulacastrum. Experiments were conducted on 45 days old plants subjected to 250 and 1,000 mM NaCl stress for 2–8 days. Plants showed no
significant change in growth parameters (shoot length, dry weight, and water content) at 250 mM NaCl as compared to control.
However, growth of plants was significantly affected at 1,000 mM NaCl. The differential growth behaviour could be attributed
to a greater decline in the energetic parameters (in terms of ratios of NADP/NADPH and ATP/ADP) at 1,000 mM NaCl than at 250 mM
NaCl. The osmotic stress imposed to plants at 250 mM NaCl was presumably balanced by the accumulation of sodium ions (Na+), an energetically favorable process, and did not require an increased synthesis of proline. In contrast, to counter osmotic
stress at 1,000 mM NaCl, plants accumulated Na+ as well as proline and were, therefore, energetically stressed. Further, the response of enzymatic and molecular antioxidants
at 1,000 mM was either close to or even lower than that at 250 mM, which resulted in oxidative damage at 1,000 mM, particularly
on longer durations. In conclusion, it is suggested that altered redox and energetic status of the plants could play a key
role in mediating the tolerance of Sesuvium under salinity stress. 相似文献
30.
Callus cultures from nodal and leaf explants of Phyllanthus amarus were established on Murashige and Skoog (MS) medium with various combinations of auxins and cytokinins. The leaf-derived
callus induced on 2.26 μM 2,4-dichlorophenoxyacetic acid (2, 4-D) + 2.32 μM Kinetin (Kin) upon transfer to medium containing
thidiazuron (TDZ) exhibited higher shoot regeneration (32.4 ± 1.3 shoots per culture). Four-week-old shoots rooted readily
on 1.5 μM Indol acetic acid (IAA)-containing medium and were successfully acclimatized with 98% survival. The lignans, Phyllanthin
(PH) and Hypohyllanthin (HPH), of leaf extracts from naturally grown plants were identified by using TLC, HPLC and H1-NMR.
The PH and HPH production in the regenerated shoots was compared to their production in callus cultures, plants under field
conditions and in naturally grown plants. The regenerated shoots on MS + 2.27 μM TDZ produced about two times higher PH and
HPH than the leaves of naturally grown plant. The present study provides a useful system for further studies on in vitro morphogenesis,
elicitor-assisted production of PH and HPH and A. rhizogenes-mediated genetic transformation in Phyllanthus amarus. 相似文献