PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Monensin”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1994

Mechanisms involved in serum-dependent inactivation of the immunotoxin enhancers monensin and carrier-protein-monensin.

The immunotoxin-enhancing properties of monensin and of human-serum-albumin-monensin conjugates are severely impaired in the presence of human serum. In this study we have therefore investigated the interaction between serum proteins and monensin leading to the inactivation of monensin function as immunotoxin potentiator. We found that the binding of monensin-specific mAb to thioether-cross-linked or disulfide-cross-linked protein-monensin conjugates is negatively affected by serum, as indicated by immunoenzymic (ELISA) and radioimmunobinding analysis. Size-exclusion chromatography of serum samples indicated that the greatest blocking effect is due to protein components of 40-90 kDa eluting as a broad peak (peak 4). Analysis of the proteins contained within peak 4 by ion-exchange chromatography followed by microsequencing revealed that the major components of peak no. 4 were transferrin, human serum albumin and immunoglobulin fragments. Investigations on the nature of the interactions between serum proteins and monensin leading to monensin inactivation were conducted by affinity chromatography of serum on immobilized human-serum-albumin-monensin conjugates, size-exclusion chromatography, SDS/PAGE analysis of serum-treated human-serum-albumin-monensin conjugates, and evaluation of the stability of immobilized human-serum-albumin-bound 125I-monensin following treatment with serum. Addition of esterase inhibitors (e.g. EDTA, 4-nitrophenyl phosphate) or prior treatment of the serum at 56 degrees C partially reversed the serum effects observed. We conclude that serum proteins block the immunotoxin-enhancing effect of monensin and of human-serum-albumin-monensin conjugates by multiple mechanisms involving hydrophobic and covalent interactions and enzyme-mediated cleavage of protein-bound monensin.

Amino Acid Sequence↗
PubMed1992

Some growth and metabolic characteristics of monensin-sensitive and monensin-resistant strains of Prevotella (Bacteroides) ruminicola.

New strains with enhanced resistance to monensin were developed from Prevotella (Bacteroides) ruminicola subsp. ruminicola 23 and P. ruminicola subsp. brevis GA33 by stepwise exposure to increasing concentrations of monensin. The resulting resistant strains (23MR2 and GA33MR) could initiate growth in concentrations of monensin which were 4 to 40 times greater than those which inhibited the parental strains. Resistant strains also showed enhanced resistance to nigericin and combinations of monensin and nigericin but retained sensitivity to lasalocid. Glucose utilization in cultures of the monensin-sensitive strains (23 and GA33) and one monensin-resistant strain (23MR2) was retarded but not completely inhibited when logarithmic cultures were challenged with monensin (10 mg/liter). Monensin challenge of cultures of the two monensin-sensitive strains (23 and GA33) was characterized by 78 and 51% decreases in protein yield (milligrams of protein per mole of glucose utilized), respectively. Protein yields in cultures of resistant strain 23MR2 were decreased by only 21% following monensin challenge. Cell yields and rates of glucose utilization by resistant strains GA33MR were not decreased by challenge with 10 mg of monensin per liter. Resistant strains produced greater relative proportions of propionate and less acetate than the corresponding sensitive strains. The relative amounts of succinate produced were greater in cultures of strains 23, GA33, and 23MR2 following monensin challenge. However, only minor changes in end product formation were associate with monensin challenge of resistant strain GA33MR. These results suggest that monensin has significant effects on both the growth characteristics and metabolic activities of these predominant, gram-negative ruminal bacteria.

Bacterial Proteins↗
PubMed1983

Monensin-resistant bacteria in the rumens of calves on monensin-containing and unmedicated diets.

Total and monensin-resistant anaerobic bacterial populations and volatile fatty acid concentrations were examined in the rumens of steers fed monensin-containing (33 mg/kg) and unmedicated diets. Total anaerobic counts on a habitat-simulating medium ranged from 7.1 X 10(8) to 7.1 X 10(9) CFU/g of rumen ingesta and were not significantly different in animals fed the two diets. The mean percentage of the anaerobic population resistant to monensin (10 micrograms/ml) was significantly greater in animals receiving the monensin-supplemented diet for 33 days than in those receiving the unmedicated diet (63.6 and 32.8%, respectively). Treatment group differences in monensin resistance tended to develop later than characteristic differences in acetate/propionate ratios. Relative proportions of resistant organisms in monensin-fed animals remained significantly greater for at least 18 days after monensin was deleted from the ration, whereas acetate/propionate ratios increased to values comparable to those in the control within 10 days. These data suggest that monensin-resistant bacteria may be present in greater numbers in the rumens of animals fed monensin-supplemented diets. However, greater proportions of monensin-resistant organisms were not necessarily associated with altered fermentation patterns.

Anaerobiosis↗
PubMed1993

Effect of monensin on plant Golgi: re-examination of the monensin-induced changes in cisternal architecture and functional activities of the Golgi apparatus of sycamore suspension-cultured cells.

We have re-examined the effects of the ionophore monensin on the Golgi apparatus of sycamore maple suspension-cultured cells using a combination of high pressure freezing, immunocytochemical and biochemical techniques. Exposure of the cells to 10 microM monensin, which reduces protein secretion by approximately 90%, resulted first in the swelling of the trans-Golgi network, then of the trans-most trans-cisterna, the remaining trans-cisternae, and finally of the cis and medial cisternae. We postulate that these different rates of swelling reflect an underlying hierarchy of compartmental acidification with the trans-Golgi network being the most acidic compartment. Recovery occurred in the reverse sequence. Previous studies have suggested that the large swollen vesicles that accumulate in the cytoplasm of monensin-treated cells arise from the swelling and detachment of entire trans-cisternae. However, based on the many membrane blebbing configurations seen in association with the trans-Golgi network and the trans-Golgi cisternae of monensin-treated cells, and the fact that the surface area of the trans-Golgi cisternae is about five times greater than the surface area of the swollen vesicles, it appears that the swollen vesicles are produced by a budding mechanism. After 35-40 min of monensin treatment, cells with smaller, non-swollen, compact Golgi stacks began to appear and rapidly increased in number, contributing > 60% of the cell population after 60 min and > 80% after 100 min. In contrast, large numbers of swollen vesicles persisted in the cytoplasm of all cells for over 100 min. Since azide treatment of monensin-treated cells can prematurely induce the unswelling response and cellular ATP levels drop substantially after 45 min of monensin treatment, we propose that un-swelling of the Golgi stacks is due to a monensin-induced decline in ATP levels in the cells. Immunocytochemical labeling of the high pressure frozen cells with anti-xyloglucan antibodies demonstrated that the concentration of xyloglucan, a hemicellulose, in the swollen vesicles increased with time. This increase in vesicle contents may explain why these swollen vesicles do not contract in parallel with the Golgi stacks. In vivo labeling experiments with [3H]fucose, [3H]UDP-glucose and [3H]leucine demonstrated that monensin-treatment not only inhibited protein secretion, but also cellulose synthesis. Protein synthesis, on the other hand, was reduced only slightly during the first 30 min of treatment, but quite strongly between 30 and 60 min, consistent with the observed drop in ATP levels after > 40 min of exposure to monensin.(ABSTRACT TRUNCATED AT 400 WORDS)

Cells, Cultured↗
PubMed1999

Effects of different concentrations of monensin and monensin withdrawal upon the control of coccidiosis in the turkey.

The efficacy of different concentrations of monensin in turkeys exposed to field isolates of Eimeria and the effect of the withdrawal of monensin from their diet were investigated. Results of a battery study indicated that 66 ppm monensin was effective against three species of Eimeria in the turkey. In floor pens in which poults were exposed to infection, use of 59.5, 79.4, and 99.2 ppm monensin resulted in reduced mortality and improved feed conversion at 3 wk of age compared with birds that had received no medication. Poults given 59.5 ppm monensin weighed more and had a better feed conversion at 3 wk than poults given 79.4 or 99.2 ppm monensin, but at 10 wk no differences in the body weight or feed conversion of poults given different concentrations of drug were apparent. At 14 wk (and from 10 to 14 wk), poults that had been given 99.2 ppm monensin had a lower feed intake and weighed less than birds that had been given 59.5 ppm of the drug but there were no significant differences in feed conversion. There was no significant difference in the weight gain or feed conversion of poults from 10 to 14 wk of age whether monensin was present in the feed or had been withdrawn. No evidence of compensatory growth was found in the present study.

Animals↗
PubMed1985

Effect of monensin on the synthesis, maturation and secretion of vesicular stomatitis virus proteins in a monensin-resistant Chinese hamster ovary cell line.

We compared the effects of the cationic ionophore, monensin, on the synthesis, maturation and release of vesicular stomatitis virus (VSV) in cultures of Chinese hamster ovary (CHO) cells and the monensin-resistant clone, MonR-31. Our results depended on the dose and time of the addition of monensin to the infected cells, from 1 h prior to VSV infection to 1 h after infection. VSV production was more resistant in MonR-31 than in CHO cells when the ionophore was added 1 h prior to VSV infection. Monensin added 1 h after VSV infection showed the opposite phenomenon; release of virus particles into the medium was 10- to 10(5)-fold less in MonR-31 cells than in CHO cells, and the intracellular virus number in the resistant cells was one-third to one-fourth of that in the parental CHO cells. Syntheses of all virus-associated G, N and M proteins were inhibited in both cell lines by monensin, but especially so in the MonR-31 cells. There were no marked qualitative changes in the biochemical properties of viral glycoprotein G in virus-infected CHO and MonR-31 cells treated with monensin after virus infection. An endoglycosidase H-resistant G with a molecular weight smaller than that of normal G and attachments of palmitate or fucose on the truncated G protein appeared. Alteration of the secretion of as well as the synthesis of the enveloped virus is discussed in relation to the monensin susceptibility of the resistant MonR-31 clone.

Animals↗
PubMed1995

Effect of monensin and monensin and tylosin combination on feed intake variation of feedlot steers.

A trial involving four commercial feedlots and an individual feeding trial evaluated the effect of monensin and monensin/tylosin on intake variation and deaths from digestive disorders. Four commercial feedlots in Texas and Colorado fed 2,904 yearling crossbred steers (340 kg) high-grain diets containing approximately 82% grain, 8% silage and alfalfa hay, 4% fat, and 6% supplement (DM basis). Steers were allotted randomly to one of three monensin/tylosin levels: 1) no monensin or tylosin (control); 2) 22 mg/kg of monensin and 11 mg/kg of tylosin; or 3) 33 mg/kg of monensin and 11 mg/kg of tylosin. Monensin/tylosin reduced DMI (P < .05) and improved ADG (P < .05) and feed efficiency (P < .01). Intake variation associated with dry matter offered per pen was not different among treatments. In the individual feeding trial, feeding 27 mg/kg of monensin reduced (P < .10) DMI variation during grain adaptation and during d 57 to 70 and d 97 to 110 compared with the control (no monensin) diet. The magnitude of intake variance was 5 to 10 times greater with individually fed steers than with steers fed in the commercial feedlot pens. When the DMI of the individually fed steers were averaged and treated as a pen of steers, DMI variance was reduced drastically and was not different between treatments. We interpret these data to indicate that monensin and monensin/tylosin reduce feed intake variation among individual steers within a pen of steers. Pen means mask individual animal variation to the point that it is difficult to detect treatment differences.

Animals↗
PubMed2002

Monensin mediates a rapid and selective transport of Pb(2+). Possible application of monensin for the treatment of Pb(2+) intoxication.

The carboxylic acid ionophore monensin, known as an electroneutral Na(+) ionophore, an anticoccidial agent, and a growth-promoting feed additive in agriculture, is shown to be highly efficient as an ionophore for Pb(2+) and to be highly selective for Pb(2+) compared with other divalent cations. Monensin transports Pb(2+) by an electroneutral mechanism in which the complex PbMonOH is the transporting species. Electrogenic transport via the species PbMon(+) may also be possible. Monensin catalyzed Pb(2+) transport is little affected by Ca(2+), Mg(2+), or K(+) concentrations that are encountered in living systems. Na(+) is inhibitory, but its effectiveness at 100 mm does not exceed approximately 50%. The poor activity of monensin as an ionophore for divalent cations other than Pb(2+) is consistent with the pattern of complex formation constants observed in the mixed solvent 80% methanol/water. This pattern also explains why Ca(2+), Mg(2+), and K(+) are ineffective as inhibitors of Pb(2+) transport, but it does not fully explain the actions of Na(+), where kinetic features of the transport mechanism may also be important. When given to rats at 100 ppm in feed together with Pb(2+) at 100 ppm in drinking water, monensin reduces Pb accumulation in several organs and tissues. It also accelerates the excretion of Pb that was accumulated previously and produces this effect without depleting the organs of zinc or copper. Monensin, used alone or in combination with other agents, may be useful for the treatment of Pb intoxication.

Animals↗
PubMed1999

Role of crotonyl coenzyme A reductase in determining the ratio of polyketides monensin A and monensin B produced by Streptomyces cinnamonensis.

The ccr gene, encoding crotonyl coenzyme A (CoA) reductase (CCR), was cloned from Streptomyces cinnamonensis C730.1 and shown to encode a protein with 90% amino acid sequence identity to the CCRs of Streptomyces collinus and Streptomyces coelicolor. A ccr-disrupted mutant, S. cinnamonensis L1, was constructed by inserting the hyg resistance gene into a unique BglII site within the ccr coding region. By use of the ermE* promoter, the S. collinus ccr gene was expressed from plasmids in S. cinnamonensis C730. 1/pHL18 and L1/pHL18. CCR activity in mutant L1 was shown to decrease by more than 90% in both yeast extract-malt extract (YEME) medium and a complex fermentation medium, compared to that in wild-type C730.1. Compared to C730.1, mutants C730.1/pHL18 and L1/pHL18 exhibited a huge increase in CCR activity (14- and 13-fold, respectively) in YEME medium and a moderate increase (3.7- and 2. 7-fold, respectively) in the complex fermentation medium. In the complex fermentation medium, S. cinnamonensis L1 produced monensins A and B in a ratio of 12:88, dramatically lower than the 50:50 ratio observed for both C730.1 and C730.1/pHL18. Plasmid (pHL18)-based expression of the S. collinus ccr gene in mutant L1 increased the monensin A/monensin B ratio to 42:58. Labeling experiments with [1, 2-(13)C(2)]acetate demonstrated the same levels of intact incorporation of this material into the butyrate-derived portion of monensin A in both C730.1 and mutant C730.1/pLH18 but a markedly decreased level of such incorporation in mutant L1. The addition of crotonic acid at 15 mM led to significant increases in the monensin A/monensin B ratio in C730.1 and C730.1/pHL18 but had no effect in S. cinnamonensis L1. These results demonstrate that CCR plays a significant role in providing butyryl-CoA for monensin A biosynthesis and is present in wild-type S. cinnamonensis C730.1 at a level sufficient that the availability of the appropriate substrate (crotonyl-CoA) is limiting.

Acetates↗
PubMed1997

Effects of monensin on tropoelastin metabolism in vascular smooth muscle cells: monensin causes intracellular degradation of accumulated tropoelastin.

Treatment with 80 nM monensin for 48 h resulted in impairment of tropoelastin secretion during the initial 6 h and subsequent reduction of tropoelastin synthesis from 18 to 48 h to one-tenth. The steady state level of tropoelastin mRNA started to decrease at 6 h and reached one-fifth of the control level by 48 h. A pulse-chase experiment after 24 h monensin treatment demonstrated that half of the accumulated tropoelastin in the cells was rapidly degraded within 120 min. These results indicate that the marked reduction in tropoelastin synthesis from 6 to 48 h treatment may be caused by both a reduction in the tropoelastin mRNA level and accelerated intracellular degradation of tropoelastin. Thus, monensin modulates tropoelastin expression through pretranslational and posttranslational mechanisms.

Animals↗
PubMed1994

Studies on chemical modification of monensin. V. Synthesis, sodium ion permeability, antibacterial activity, and crystal structure of 7-O-(4-substituted benzyl)monensins.

7-O-(4-Substituted benzyl)monensins (3a-g) were synthesized from monensin (1), and their lipophilicity, antibacterial activity, and Na+ ion permeability were examined. 7-O-(4-Ethylbenzyl)monensin (3e) showed the largest Na+ ion permeability, but 3c,f,g showed smaller Na+ ion permeability than 7-O-benzylmonensin (2) in spite of higher lipophilicity. An X-ray study of the sodium salt of 3e revealed that the benzyl group was located over the position between the D and E rings, and that the ethyl substituent on the benzyl group was close to the C(28) methyl group on the E ring.

Anti-Bacterial Agents↗
PubMed1997

Studies on chemical modification of monensin. VI. Preparation of C-7 modified monensins via protected 7-oxomonensin and evaluation of their ion transport activity.

7-Carboxymethylmonensin (3), 7-aminomonensin (4), and 7-oxomonensin (5) were synthesized via protected 7-oxomonensin (2), which is expected to be a useful intermediate for the preparation of various monensin derivatives. intermediate for the preparation of various monensin derivatives. Compounds 3-5 exhibited smaller ion transport activity than monensin (1).

Calcium↗
PubMed2001

Studies on chemical modification of monensin IX. Synthesis of 26-substituted monensins and their Na+ ion transport activity.

The C-26 modified monensin derivatives, 26-O-benzoylmonensin (3), 26-O-benzylmonensin (4) and 26-phenylaminomonensin (5) were prepared from monensin (1). Na+ ion transport activity through biological membrane and antibacterial activity of 3-5 were evaluated and compared with the activities reported for a 26-phenylurethane derivative (2). Among these compounds, 5 showed the largest Na+ ion transport and antibacterial activities. In these compounds, the formation of head-to-tail hydrogen bonds was suggested to be an important factor for Na+ ion transport and antibacterial activities.

Anti-Infective Agents↗
PubMed1990

Selection for resistance to monensin, nicarbazin, and the monensin plus nicarbazin combination.

Two series of experiments were conducted to assess the relative ability of strains of Eimeria acervulina and Eimeria tenella to develop resistance to monensin (MON), nicarbazin (NIC), and the monensin plus nicarbazin combination (MON plus NIC). The studies were designed so that drug concentrations in the selection experiments were increased whenever possible. During selection, E. acervulina increased its reproductive index in the presence of NIC or MON plus NIC, equivalent selection in the presence of MON resulted in only a slight increase in reproductive ability. Eimeria tenella, however, was unable to increase its reproductive capacity to the respective drugs. Sensitivity tests after 60 generations of selection revealed that patterns of resistance development for E. acervulina and E. tenella corresponded with the changes in reproductive indices established in the selection experiments. Thus, results of these tests indicate that E. acervulina possesses the ability to develop resistance to NIC and MON plus NIC. Under essentially the same conditions of selection, E. tenella developed only partial resistance to the respective drugs.

Animals↗
PubMed1992

Blocking effect of human serum but not of cerebrospinal fluid on ricin A chain immunotoxin potentiation by monensin or carrier protein-monensin conjugates.

The potentiation of monoclonal antibody/ligand toxin (immunotoxin) cytotoxicity by the ionophore monensin (Mo) or by human serum albumin-monensin (HSA-Mo) conjugates was investigated. Since disulfide cross-linked HSA-Mo (HSA-SPDP-Mo) is rapidly inactivated by human serum (M. Colombatti et al., Cancer Res., 50: 1385-1391, 1990), we synthesized thioether cross-linked HSA-Mo conjugates (HSA-SIA-Mo). HSA-SIA-Mo is resistant to treatment with reducing agents (e.g., glutathione, dithiothreitol) and shows potentiating activity identical to that of Mo or of HSA-SPDP-Mo, enhancing immunotoxin (IT) cytotoxicity 45-35,000-fold. Human leukemic and tumor cell lines are highly sensitive to treatment with IT in combination with Mo, HSA-SPDP-Mo, or HSA-SIA-Mo (concentration required to inhibit protein synthesis by 50%, 10(-10)-2.5 x 10(-13) M). IT potentiation by both types of HSA-Mo conjugates, however, is inhibited by whole human serum. In contrast, human cerebrospinal fluid has no effect on the potentiation of IT by Mo or HSA-Mo conjugates. The serum blocking factors reside mostly in a Mr 40,000-90,000 protein fraction. Serum components of low molecular weight (less than 10,000) show no detectable effect upon the stability of HSA-Mo conjugates. The toxicity of HSA-SIA-Mo in vivo was investigated by intrathecal injections in rats. Concentrations of up to 60 micrograms/kg can be injected into the brain with only transient neurological sequelae. We therefore conclude that if the systemic delivery of HSA-Mo conjugates for the potentiation of ricin A chain-IT presents some limitations due to the blocking effect of serum, the application of HSA-Mo conjugates in combination with ricin A chain-IT for regional tumor therapy in the brain appears more promising.

Ammonium Chloride↗