Cause Of Growth Inhibition Research Articles

Overexpression of peptide-methionine sulfoxide reductase in Saccharomyces cerevisiae and human T cells provides them with high resistance to oxidative stress.

The yeast peptide-methionine sulfoxide reductase (MsrA) was overexpressed in a Saccharomyces cerevisiae null mutant of msrA by using a high-copy plasmid harboring the msrA gene and its promoter. The resulting strain had about 25-fold higher MsrA activity than its parent strain. When exposed to either hydrogen peroxide, paraquat, or 2,2'-azobis-(2-amidinopropane) dihydrochloride treatment, the MsrA overexpressed strain grew better, had lower free and protein-bound methionine sulfoxide and had a better survival rate under these conditions than did the msrA mutant and its parent strain. Substitution of methionine with methionine sulfoxide in a medium lacking hydrogen peroxide had little effect on the growth pattern, which suggests that the oxidation of free methionine in the growth medium was not the main cause of growth inhibition of the msrA mutant. Ultraviolet A radiation did not result in obvious differences in survival rates among the three strains. An enhanced resistance to hydrogen peroxide treatment was shown in human T lymphocyte cells (Molt-4) that were stably transfected with the bovine msrA and exposed to hydrogen peroxide. The survival rate of the transfected strain was much better than its parent strain when grown in the presence of hydrogen peroxide. These results support the proposition that the msrA gene is involved in the resistance of yeast and mammalian cells to oxidative stress.

Growth inhibition of Rhodococcus sp. strain RHA1 in the course of PCB transformation

Growth of a PCB degrader Rhodococcus sp. RHA1 on biphenyl and ethylbenzene was inhibited by 100 μg/ml PCB 48. A PCB tolerant derivative of RHA1 designated RCD1 was deficient in growth on biphenyl. Southern hybridization experiments suggested that RCD1 has the bphDE gene deletion in a 390-kb linear plasmid of RHA1. The bphD gene complementation restored growth deficiency on biphenyl and growth inhibition on ethylbenzene by PCB 48, indicating that PCB metabolites are the cause of growth inhibition.

キュウリの初期生長と無機栄養に及ぼす高気温と高地温の影響

Relative contributions of supraoptimal air and root-zone temperatures on the growth inhibition of cucumber (Cucumis sativus L.) during hot seasons were evaluated. Seedlings of a Chinese cultivar, Sangoh (Ji huang gua 3) and a Japanese cultivar, Sharp I were grown in water culture for 8 days in controlled environment rooms. The environmental conditions were : 26/26 °C, 26/37 °C, 37/26 °C or 37/37 °C daytime air/root-zone temperature regimes (air temperature in the night was 5 °C lower than that in the day), 80/90 % relative air humidity, and a 15-hr photoperiod of ca. 480 μmol•m-2•s-1 PPFD.Temperature of leaves was approximately equal to air temperature during the daytime. Although plants thrived best at 26/26 °C and worst at 37/37 °C combinations, when growth at 26/37 °C and 37/26 °C regimes was compared, high air temperature was more inhibitory than high root-zone temperature. Root growth, leaf expansion rate, leaf water content, photosynthetic rate and leaf mineral concentrations were reduced more severely by high root-zone temperature. Seedlings of 'Sangoh' were significantly more tolerant to high root-zone temperature than were those of 'Sharp I'. Possible causes of growth inhibition by high air temperature compared to that by high root-zone temperature and the mechanisms of the cultivarietal difference in thermotolerance of cucumber plants are discussed.

The Role of Cell Wall Adjustments in Plant Resistance to Water Deficits

Reductions in rates of cell and tissue growth are a commonly observed response to water deficits resulting from drought or soil salinity. These can lead to reductions in plant size and yields. More severe stress can lead to accelerated death and complete loss of yields. This review deals with the final biophysical links in the chain of events underlying inhibition of growth in crop plants exposed to water deficits. It first examines and rejects the notion that a stress‐induced reduction in cellular turgor pressure is necessarily a primary cause of growth inhibition. Data supporting the involvement of an additional and often overlooked biophysical response to water deficits are then reviewed: This response involves changes in tissue extension capacity, as a result of hardening (or softening) of expanding cell walls, and is termed cell wall adjustment. Wall hardening should increase the capacity of expanding cells to maintain turgor pressure but also acts to inhibit rates of cell expansion growth. The inhibition of cell expansion can lead to reductions in leaf area that limit rates of transpirational loss of soil water reserves; in nonirrigated crops exposed to terminal drought environments, this adaptation may prolong survival and allow time for completion of reproductive development. Conversely, wall hardening responses to intermittent water deficit episodes, e.g., in irrigated crops, could be undesirable. The survival of irrigated crops is largely assured and induction of wall hardening in the intervals between irrigation could unnecessarily reduce growth and yields. Appropriate manipulation of cell wall adjustments, via selection, breeding, or genetic engineering, could prove useful for the development of more stress‐resistant crop plants suited to irrigated or nonirrigated environments.

In vivo growth inhibition of L1210 leukemia by 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A), a new inhibitor of S-adenosylmethionine decarboxylase.

We studied the in vivo growth-inhibitory effect of the new S-adenosylmethionine decarboxylase inhibitor 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A). L1210-bearing DBA-2 mice were treated with increasing CGP 48664A doses from 1 day after i.p. L1210 cell inoculation. Treatment was continued for 4 days, after which all mice were killed. CGP 48664A caused dose-related exponential decreases of L1210 cell numbers and spermidine and spermine contents. Putrescine contents increased exponentially. Polyamine changes in spleen and liver were less profound. L1210 growth inhibition was not accompanied by changes in cell cycle phase distribution. It is concluded that CGP 48664A is an effective inhibitor of S-adenosylmethionine decarboxylase but that CGP 48664A-induced changes in intracellular polyamine compositions are not necessarily the cause of growth inhibition.

Growth and development of sorghum leaves under conditions of NaCl stress: possible role of some mineral elements in growth inhibition

Elongating leaf tissue, which in monocotyledonous species is a small region located near the leaf base, requires a continuous supply of nutrients to maintain cell expansion and is, therefore, highly susceptible to nutrient disturbances. The objective of this work was to investigate the effects of salinity on the availability of nutrient elements within the elongating region of sorghum (Sorghum bicolor [L.] Moench, cv. ‘NK 265’) leaves, in order to assess their possible role in salt-induced growth inhibition. Plants grown in complete nutrient solution were exposed to 1 or 100 mol·m−3 NaCl salinity. Spatial distributions of biomass and bulk tissue K, Na, Ca, and Mg were determined on a millimeter scale in the growth zone of leaf 6, while it was growing rapidly just after emergence from the encircling whorl of older leaf sheaths. Spatial patterns of net rates of element deposition were also calculated. Potassium, Ca, Mg, and Na exhibit along the leaf growing zone, distinct spatial concentration patterns which are changed by exposure to saline stress. Salinity induces a decrease in K concentration and deposition rate throughout the elongation zone. The inhibition of K deposition rate due to salinity increases with distance from the leaf base, as did the inhibition of growth. Salinity induces a dramatic decrease in Ca that could also be responsible for leaf growth inhibition. The concentration of Mg is lower under salt stress in the basal part of the growing region, where Na is preferentially accumulated. Since the base of the growth zone is where growth is least affected by salinity, high levels of Na are not the cause of growth inhibition in this salt-affected leaf tissue.

Ammonium ion inhibition of Pinus strobus L. callus growth

Effects of NO 3 − and NH 4 + oons on growth of Pinus strobus L. callus were studied. Callus tissue was obtained from hypocotyl segments of P. strobus seedlings and was maintained on a modified Murashige and Skoog's medium supplemented with 0.2 mg/l α-napthaleneacetic acid (NAA). The tissue could be repeatedly subcultured on a medium containing KNO 3 as the sole nitrogen source in the medium. However, the callus growth was totally inhibited when NH 4Cl was used as the nitrogen source. The inhibitory effect of NH 4Cl could be eliminated by providing appropriate amounts of KNO 3 in the medium in addition to NH 4Cl. The inhibitory effect on callus growth was found to be due to NH 4 + and not Cl −ions; good callus growth occurred on media containing KCl. Experiments suggested that acidification of the medium due to NH 4 + ions was not the cause of growth inhibition. Growth of P. strobus callus seems to be inhibited due to its inability to utilize NH 4 + as a source of nitrogen, which results in accumulation of toxic levels of NH 4 + in the tissue. Experimental evidence also suggests involvement of glutamine synthetase in NH 4 +-induced inhibition of P. Strobus callus growth.

Inhibition of Homoserine Dehydrogenase I by L-Serine in Escherichia coli1

We have reported that a major cause of growth inhibition of Escherichia coli by L-serine is its inhibition of homoserine dehydrogenase I (HDH I), which is involved in the biosyntheses of threonine and isoleucine [Hama, H., Sumita, Y., Kakutani, Y., Tsuda, M., & Tsuchiya, T. (1990) Biochem. Biophys. Res. Commun. 168, 1211-1216]. However, Patte et al. reported that L-serine does not inhibit HDH I [Patte, J.-C., Truffa-Bachi, P., & Cohen, G.N. (1966) Biochim. Biophys. Acta 128, 426-439]. In studies on the reason for these discrepant results, we found that the concentration of K+ and the pH in the assay mixture strongly influenced the inhibitory effect of L-serine. L-Serine strongly inhibited the HDH I activities in both the forward and reverse reactions between aspartate semialdehyde and homoserine at a physiological K+ concentration (100 to 200 mM) and physiological pH (7.5) for E. coli cells. On the other hand, two well-known inhibitors of HDH I, L-threonine and L-cysteine, strongly inhibited the activity regardless of the K+ concentration and pH.

Sites of action of pyridazinone herbicides (SANDOZ 9785 and 9789) onChlorella protothecoides

WhenChlorella protothecoides cells were grown in the presence of 30, 100 and 300 μM of SANDOZ 9785 and 9789, there was a significant decrease in cell number and packed cell volume as compared to control. SANDOZ 9789 seems to be a stronger inhibitor of growth than SANDOZ 9785. The immediate effect of pyridazinone herbicides on photosynthesis showed that SANDOZ 9789 is a weaker inhibitor than SANDOZ 9785. There was no direct correlation between the inhibition of growth and photosynthesis by the herbicide treatment suggesting that the inhibition of photosynthesis is not the primary cause of growth inhibition. Experiments on growth, carried out with non-photosynthetic and non green cells also support this suggestion. The observed increase in cell size when the cells grown with SANDOZ 9785 suggests that cell division was inhibited by SANDOZ 9785.

Role of red cells in preventing the growth of platelet aggregation

Using high-resolution real-time two-dimensional ultrasound, we have investigated the role of red cells in the growth of already established platelet aggregates under controlled flow conditions. Platelet rich plasma (PRP) was circulated in vitro in horizontally and vertically arranged tubing at mean shear rate ranging from 60 to 0 sec- , and adenosine diphosphate (ADP) was used to induce platelet aggregation. ADP-induced platelet aggregates grew in size and tende to sediment ps shear rate decreased, in particular, below 10 sec. At 0 sec −1 (stasis), large clusters of platelet aggregates formed. The addition of washed red cells to produce a hematocrit of only 2% significantly interfered with the growth and sedimentation of platelet aggregates as shear rate was reduced. Formaldehyde-hardened erythrocytes had a similar effect in preventing the growth of platelet aggregates, suggesting that mechanical collision of red cells with platelet aggregates may be the cause of growth inhibition. Therefore, the thrombotic process may be enhanced in red cell poor zones in circulation resulting from flow disturbances associated with vascular stenosis or within artificial organs and extracorporeal systems. The present study also suggested that red cell free PRP should be carefully administered therapeutically.

The effects of fluoride on cell growth of two human cell lines and on DNA and protein synthesis in HeLa cells.

The effect of sodium fluoride on the growth of two continuous human cell lines, i.e. HeLa cells and human conjunctiva clone 1-5C-4 cells, was studied. The growth of HeLa cells and clone 1-5C-4 cells was arrested nearly completely by the addition of 0.95 and 1,90 mM of sodium fluoride, respectively. DNA synthesis in HeLa cells, determined by incorporation of 3H-thymidine, was not affected appreciably for the first 24-hr period after the addition of sodium fluoride. Markedly reduced incorporation, however, occurred during the next 24-hr period. Thus, there was a discrepancy between the immediate cessation of cell division and the delayed suppression of DNA synthesis. On the other hand, a suppressive effect of sodium fluoride on protein synthesis determined by 14C-leucine incorporation was evident already during the first 24-hr period. The results indicate that the inhibition of protein synthesis is the main cause of growth inhibition.

Effects of retinoic acid on protein synthesis in cultured melanoma cells.

Retinoic acid reduces the growth rate of mouse S91 melanoma cells in culture and increases the proportion of cells in the G1 phase of the cell cycle. Because of the integral role protein synthesis has been shown to play in growth control we studied the effect of retinoic acid on the protein synthesis machinery with a cell-free system developed from the melanoma cells. This system was capable of translating endogenous mRNA, exogenous globin mRNA, and the synthetic template poly(U). Of the above activities of the protein synthesis system only the translation of endogenous mRNA was reduced significantly in the cell-free system prepared from retinoic acid-treated cells. Analyses of the amount and function of RNA revealed that treatment with retinoic acid leads to reductions in total RNA content, in the proportion of ribosomes in polysomes, in the amount of poly(A)RNA, and in the amount of polysome-associated mRNA. All these effects of retinoic acid contribute to the decrease in protein synthesis activity of treated cells. Two-dimensional electrophoresis analysis of L-[35S]methionine-labeled proteins produced by untreated and treated cells revealed only a few quantitative differences. We suggest that retinoic acid-induced suppression of protein synthesis activity may be the cause for growth inhibition.

Specific ion effect as a probable cause of growth inhibition under saline conditions

The replacement of carboxy-proton of IAA, plays an important role in the process of growth under saline conditions. Appreciable changes in pH have ben observed in the presence of CO3 −2 and HCO3 −, and increase in pH appears to be caused owing to the formation of unstable complex of IAA, which soon hydrolyzes and gives alkalinity. The pH change thus achieved favours IAA oxidase activity; therefore, suppression of growth is resulted in CO3 −2 and HCO3 − medium. In the presence of SO4 −2 and Cl− salts slight lowering of pH takes place which does not favour IAA oxidase activity. It is therefore, presumed that anion (CO3 −2, HCO3 −, SO4 −2 and Cl−) controls the process of growth and development through the alteration of pH of the medium.

ATP concentration in Escherichia coli during oxygen toxicity

Escherichia coli, strain E-26, grown in defined salts medium with glucose as the sole carbon and energy source, contained 1.50 ± 0.16 · 10 6 molecules of ATP/cell. ATP was extracted with HClO 4 and assayed with a Dupont Luminescence Biometer using the luciferin-luciferase assay. Exposure during exponential growth at 37°C to 4.2 atm of oxygen resulted in complete growth cessation within 5 min, and to cyclic changes in cellular ATP concentration over a 2 h period. However, significant decrease in cellular ATP concentration occurred after growth inhibition in hyperbaric oxygen; hence, lack of ATP was not the cause of growth inhibition from oxygen toxicity.

Mis-regulation of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthetase does not account for growth inhibition by phenylalanine in Agmenellum quadruplicatum.

The growth of the blue-green bacterium, Agmenellum quadruplicatum, is inhibited in the presence of l-phenylalanine. This species has a single, constitutively synthesized 3-deoxy-d-arabino-heptulosonate 7-phosphate (DAHP) synthetase. l-Phenylalanine inhibits DAHP synthetase non-competitively with respect to both substrate reactants. Other aromatic amino acids do not inhibit the activity of DAHP synthetase. A common expectation for branch-point enzymes such as DAHP synthetase is a balanced pattern of feedback control by all of the ultimate end products. It seemed likely that growth inhibition might equate with defective regulation within the branched aromatic pathway. Accordingly, the possibility was examined that mis-regulation of DAHP synthetase by l-phenylalanine in wild-type cells causes starvation for precursors of the other aromatic end products. However, the molecular basis for growth inhibition cannot be attributed to l-phenylalanine inhibition of DAHP synthetase for the following reasons: (i) DAHP synthetase enzymes from l-phenylalanine-resistant mutants are more, rather than less, sensitive to feedback inhibition by l-phenylalanine. (ii) Shikimate not only fails to antagonize inhibition, but is itself inhibitory. (iii) Neither the sensitivity nor the completeness of l-phenylalanine inhibition of the wild-type enzyme in vitro appears sufficient to account for the potent inhibition of growth in vivo by l-phenylalanine. The dominating effect of l-phenylalanine in the control of DAHP synthetase appears to reflect a mechanism that prevents rather than causes growth inhibition by l-phenylalanine. The alteration of the control of DAHP synthetase in mutants selected for resistance to growth inhibition by l-phenylalanine did indicate that the cause for this metabolite vulnerability can be localized within the aromatic amino acid pathway. Apparently, an aromatic intermediate (between shikimate and the end products) accumulates in the presence of l-phenylalanine, causing toxicity by some unknown mechanism. It is concluded that phenylpyruvate, potentially formed by transamination of l-phenylalanine, is an unlikely cause of growth inhibition. Although several significant questions remain unanswered, our results suggest that single-effector control of DAHP synthetase, the first regulatory enzyme activity of a branched pathway, may be more appropriate than it would seem a priori.

A Correlation between Growth Inhibition of the First Leaf and Mitotic Delay after Irradiation of Soaking Barley Seeds

After low dose irradiation during early soaking of barley seeds, the cause of growth inhibition of the first leaf was cytologically investigated. It was suggested that the growth inhibition was attributable to division delay of the meristem cells owing to temporal G2-block.

Inhibitory effects of anticellular antibodies on colony formation of mouse leukemia L5178YR cells in soft agar.

Heat-inactivated antiserum in the absence of complement inhibits colony formation of mouse leukemia L5178YR cells in soft agar. Cells derived from resistant clones in these plates showed the same sensitivity to antiserum as the parent population. Agglutination of the cells was prevented by placing the antiserum dilutions over the cell-containing agar layer. This clearly indicates that cell agglutination by antiserum is not necessarily the essential cause of growth inhibition.

2-thiouridine 5′-phosphate and its inhibition of aspartate transcarbamylase

2-Thioridine 5′-phosphate (2-Thio-UMP) has been synthetized and its inhibitory effect on aspartate transcarbamylase (carbamoylphosphate: l-aspartate carbamoyltransferase, EC 2.1.3.2) investigated. 2-Thio-UMP was enzymatically synthetized from 2-thiouracil and 5-phosphoribosyl 1-pyrophosphate ( P- P-ribose- P) in a reaction catalyzed by nucleotide pyrophosphorylase obtained from Escherichia coli W. The product was isolated by thin-layer chromatography on cellulose developed with butanol-HCl. 2-Thio-UMP had a chromatographic mobility slightly greater than UMP. The ultraviolet spectrum of 2-thio-UMP was different from that of 2-thiouracil and it contained both sulfur and phosphorus. Inhibition of E. coli asparate transcarbamylase by 2-thio-UMP appears to be similar to the inhibition of this enzyme by CTP. These results support the hypothesis that inhibition of aspartate transcarbamylase by nucleotides of 2-thiouracil is the major cause of growth inhibition of E. coli in medium containing 2-thiouracil. It is proposed that 2-thiouracil, following entrance into the cell, is converted to nucleotide(s) which cannot be incorporated into nucleic acids but are able to inhibit cell growth by a reduction of the catalytic activity of aspartate transcarbamylase.

Decreased ribonucleic acid levels: a possible cause of growth inhibition in zinc deficiency

Decreased ribonucleic acid levels: a possible cause of growth inhibition in zinc deficiency

Decreased ribonucleic acid levels: a possible cause of growth inhibition in zinc deficiency

Decreased ribonucleic acid levels: a possible cause of growth inhibition in zinc deficiency