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PubMed1989

Cell enlargement: one possible mechanism underlying cellular senescence.

We previously demonstrated an inverse relationship between the G1 volume of human diploid fibroblast-like (HDFL) cells obtained from foreskin tissue and clonal replicative potential. On the basis of these results, we suggested that one process underlying in vitro senescence is a progressive increase in the mean cell volume of successive progeny within clonal lineages. We now report that the size of HDFL cells, as well as of chick embryo fibroblasts, can be increased in the virtual absence of cell division by culturing at low density and at low serum concentration (0.1-1.0%). Consequent to an increase in cell size, the replicative potential of the cells is reduced to the level of later-passage cells of similar size. By clonal analysis, the populations of enlarged cells contain up to three times as many nondividing cells as do controls. In the enlarged populations, the proportion of cells producing attenuated clones (four or fewer progeny) increases by about 30%, whereas the proportion of cells yielding greater than 32 cells declines by a similar percentage. These observations lead us to propose that replicative potential may be limited by cell size, which in turn may be regulated by a kinetic relationship between cellular growth and cell division cycles.

Animals↗
PubMed2005

Low temperature stimulates cell enlargement and intracellular calcification of coccolithophorids.

Temperature effect on growth, cell size, calcium uptake activity, coccolith production was studied in coccolith-producing haptophytes, Emiliania huxleyi (Lohmann) Hay & Mohler (strain EH2) and Gephyrocapsa oceanica Kamptner (strain GO1) (Coccolithophorales, Prymnesiophyceae). E. huxleyi grew at a wider temperature range (10 degrees-25 degrees C), while G. oceanica growth was limited to warmer temperatures (20 degrees-25 degrees C). Cell size was inversely correlated with temperature. At low temperature, the enlargement of chloroplasts and cells and the stimulation of coccolith production were morphologically confirmed under fluorescent and polarization microscopes, respectively. 45Ca uptake by E. huxleyi at 10 degrees C was greatly increased after a 5-day lag and exceeded that at 20 degrees C. These results clearly showed that low temperature suppressed coccolithophorid growth but induced cell enlargement and as stimulated the intracellular calcification that produces coccoliths.

Calcification, Physiologic↗
PubMed2006

The impact of cell division and cell enlargement on the evolution of fruit size in Pyrus pyrifolia.

BACKGROUND AND AIMS: Dramatic increases in fruit size have accompanied the domestication of Pyrus pyrifolia. To evaluate the contribution of cell division and cell enlargement in the evolution of fruit size, the following study was conducted. METHODS: Three wild Pyrus and 46 cultivated Pyrus pyrifolia cultivars were selected to examine cell number/size at time of pollination and at time of fruit harvest. The period of cell division was estimated by logarithmic curve of the increasing pattern of cell number, and its correlations with maturation period and final fruit size were analysed. KEY RESULTS: Final fruit size is directly related to the number of cells produced in the period immediately following pollination. Late-maturing cultivars are larger than earlier-maturing cultivars and this is due to an extended period of cell division. CONCLUSIONS: The evolution of fruit size in P. pyrifolia has mainly resulted from shifts in the ability of cells to divide rather than to enlarge.

Biological Evolution↗
PubMed2000

CHO cell enlargement oscillates with a temperature-compensated period of 24 min.

The rate of increase in cell area of CHO cells when measured at intervals of 1 min using a light microscope equipped with a video measurement system, oscillated with a minimum period of about 24 min. The pattern of oscillations paralleled those of the 24 min period observed with the oxidation of NADH by an external cell surface or plasma membrane NADH oxidase. The increase in cell area was non-linear. Intervals of rapid increase in area alternated with intervals of rapid decrease in area. The length of the 24 min period was temperature-compensated (approximately the same when measured at 14 degrees C, 24 degrees C or 34 degrees C) while the rate of cell enlargement increased with temperature over this same range of temperatures.

Animals↗
PubMed2007

Fat cell enlargement is an independent marker of insulin resistance and 'hyperleptinaemia'.

AIMS/HYPOTHESIS: The aim of this study was to explore whether fat cell size in human subcutaneous and omental adipose tissue is independently related to insulin action and adipokine levels. MATERIALS AND METHODS: Fat cells were prepared from abdominal subcutaneous biopsies obtained from 49 type 2 diabetic and 83 non-diabetic subjects and from omental biopsies obtained from 37 non-diabetic subjects. Cell size and insulin action on glucose uptake capacity in vitro were assessed in isolated fat cells. Insulin sensitivity in vivo was assessed with euglycaemic-hyperinsulinaemic clamps. Fasting blood samples were collected and adipokines and NEFA were measured. RESULTS: Negative correlations were found between subcutaneous fat cell size and insulin sensitivity assessed as M-value during clamp and as insulin action on glucose uptake in fat cells in vitro. This was seen in non-diabetic subjects after including age, sex and BMI in the analyses. No such relationship was found in type 2 diabetic subjects. In both groups, subcutaneous fat cell size correlated positively and independently with plasma levels of leptin but not to any of the other assessed adipokines. In non-diabetic subjects, omental fat cell size was independently and negatively correlated with insulin action in subcutaneous, but not omental, fat cells in vitro. CONCLUSIONS/INTERPRETATION: Fat cell enlargement is associated with insulin resistance in non-diabetic individuals independently of BMI. This was not seen in type 2 diabetic subjects, suggesting that after development of type 2 diabetes other factors, not related to fat cell size, become more important for the modulation of insulin resistance.

Adipose Tissue↗
PubMed1981

Light or ethylene treatments induce transverse cell enlargement in etiolated maize mesocotyls.

Dark-grown maize seedlings (hybrid WF-9 x 38-11) exposed for 1 or more hours to white light and then returned to darkness developed mesocotyls with enlarged apical diameters. This swelling response was an all-or-none response, and the fraction of the seedling population that showed the response depended on seedling age at irradiation. Irradiation of the coleoptile alone was nearly as effective in causing this response as was irradiation of the nodal region of the epicotyl, but irradiation of the mesocotyl base was ineffective. Removal of the coleoptile prior to irradiation did not prevent the formation of the light-induced swelling. Exogenously applied C(2)H(4) (10 microliters per liter) for 24 hours in dark also induced swelling of the mesocotyl. The swelling induced in the intact seedlings was localized in the apical mesocotyl tissues with either light or C(2)H(4) treatment, and maximal response to both treatments occurred with 3- to 4-day-old seedlings. Swelling of the mesocotyl was the result of transverse cell enlargement, not increase of cell numbers. The evidence suggests that light and C(2)H(4) induce mesocotyl swelling in intact maize shoots by a common mechanism.

Journal Article↗
PubMed1993

Role of Expansin in Cell Enlargement of Oat Coleoptiles (Analysis of Developmental Gradients and Photocontrol).

Expansins are wall proteins that mediate a type of acid-induced extension in isolated plant cell walls (S. McQueen-Mason, D.M. Durachko, D.J. Cosgrove [1992] Plant Cell 4: 1425-1433). To assess the role of these proteins in the process of cell enlargement in living tissues, we compared the spatial and temporal growth patterns of oat (Avena sativa L.) coleoptiles with four wall properties related to expansin action. These properties were (a) the ability of isolated walls and living segments to extend in acidic buffer, (b) the ability of heat-inactivated walls to extend upon application of expansins, (c) the amount of immunologically detectable expansin in wall protein extracts, and (d) the extractable expansin activity of walls. Growth rate was maximal in the apical half of dark-grown coleoptiles and negligible in the basal region. This growth pattern correlated with properties a and b; in contrast, the amount and activity of extractable expansin (properties c and d) were reduced only in the most basal region. Upon exposure to white light, coleoptiles abruptly ceased elongation at 8 to 10 h after start of irradiation, and this cessation correlated with reductions in properties a to c. The growth cessation at 8 to 10 h also coincided with the loss of growth response to exogenous auxin and fusicoccin in excised coleoptile segments. These results lend correlative support to the hypothesis that expansin action is important for growth responses of living oat coleoptiles (e.g. responses to acidic buffers, auxin, fusicoccin, aging, and light). Our results suggest that changes in the susceptibility of the wall to expansin action, rather than changes in expansin activity, may be a key determinant of the growth patterns in oat coleoptiles.

Journal Article↗
PubMed2004

Human cytomegalovirus-induced host cell enlargement is iron dependent.

A hallmark of human cytomegalovirus (HCMV) infection is the characteristic enlargement of the host cells (i.e., cytomegaly). Because iron (Fe) is required for cell growth and Fe chelators inhibit viral replication, we investigated the effects of HCMV infection on Fe homeostasis in MRC-5 fibroblasts. Using the metallosensitive fluorophore calcein and the Fe chelator salicylaldehyde isonicotinoyl hydrazone (SIH), the labile iron pool (LIP) in mock-infected cells was determined to be 1.04 +/- 0.05 microM. Twenty-four hours postinfection (hpi), the size of the LIP had nearly doubled. Because cytomegaly occurs between 24 and 96 hpi, access to this larger LIP could be expected to facilitate enlargement to approximately 375% of the initial cell size. The ability of Fe chelation by 100 microM SIH to limit enlargement to approximately 180% confirms that the LIP plays a major role in cytomegaly. The effect of SIH chelation on the mitochondrial membrane potential (DeltaPsi(M)) and morphology was studied using the mitochondrial voltage-sensitive dye JC-1. The mitochondria in mock-infected cells were heterogeneous with a broad distribution of DeltaPsi(M) and were threadlike. In contrast, the mitochondria of HCMV-infected cells had a more depolarized DeltaPsi(M) distributed over a narrow range and were grainlike in appearance. However, the HCMV-induced alteration in DeltaPsi(M) was not affected by SIH chelation. We conclude that the development of cytomegaly is inhibited by Fe chelation and may be facilitated by an HCMV-induced increase in the LIP.

Animals↗
PubMed2002

Bone marrow fat cell enlargement and a rise in intraosseous pressure in steroid-treated rabbits with osteonecrosis.

The etiology of steroid-induced osteonecrosis (ON) is unclear. This study was designed to determine whether bone marrow fat cell size, intraosseous pressure, and blood flow rate differed between steroid-treated rabbits with ON and those without. Twenty-nine rabbits were intramuscularly injected once with 20 mg/kg of methylprednisolone acetate (MPSL), and five rabbits were injected once with physiologic saline (PS) as a control. Intraosseous pressure and blood flow rate in the proximal femur were determined before and at 2 weeks after the injection. After these measurements, both femora and humeri were histopathologically examined for the presence of ON, and size of bone marrow fat cells were morphologically examined. At 2 weeks after steroid injection, the intraosseous pressure was significantly higher in rabbits with ON than in those without (p = 0.0251), and the blood flow rate had decreased significantly more in rabbits with ON than in those without (p = 0.0051). The size of the bone marrow fat cells was significantly (p = 0.0004) larger in rabbits with ON (diameter, 63.5 +/- 5.8 microm) than in those without (diameter, 53.3 +/- 6.9 microm). Injection of PS (5 rabbits), 1 (10 rabbits), 5 (10 rabbits), and 20 (10 rabbits) mg/kg of body weight of MPSL showed that a larger dose of steroid increased both fat cell size and prevalence of ON. These results suggest that bone marrow fat cell enlargement and a rise in intraosseous pressure may be important when considering the pathophysiology of steroid-induced ON in rabbits.

Adipocytes↗
PubMed1996

Plant cell enlargement and the action of expansins.

Plant cells are caged within a distended polymeric network (the cell wall), which enlarges by a process of stress relaxation and slippage (creep) of the polysaccharides that make up the load-bearing network of the wall. Protein mediators of wall creep have recently been isolated and characterized. These proteins, called expansins, appear to disrupt the noncovalent adhesion of matrix polysaccharides to cellulose microfibrils, thereby permitting turgor-driven wall enlargement. Expansin activity is specifically expressed in the growing tissues of dicotyledons and monocotyledons. Sequence analysis of cDNAs indicates that expansins are novel proteins, without previously known functional motifs. Comparison of expansin cDNAs from cucumber, pea, Arabidopsis and rice shows that the proteins are highly conserved in size and amino acid sequence. Phylogenetic analysis of expansin sequences suggests that this multigene family diverged before the evolution of angiosperms. Speculation is presented about the role of this gene family in plant development and evolution.

Amino Acid Sequence↗
PubMed2005

Bone marrow fat-cell enlargement in early steroid-induced osteonecrosis--a histomorphometric study of autopsy cases.

Some animal studies and magnetic resonance imaging studies suggest that there may exist a relationship between abnormal lipid metabolisms and osteonecrosis. The purpose of this study was to examine the size of bone marrow fat cells in the early osteonecrosis femoral head using autopsy specimens. We compared the size of bone marrow fat cells in the viable areas in the following three autopsy groups: the early osteonecrosis group (4 femoral heads); the steroid-administered group (without osteonecrosis) (n = 10), and the normal group (n = 19). In addition, after adjusting for age and sex, the size of bone marrow fat cells was compared using multiple regression analysis. The size of bone marrow fat cells was significantly larger in the early osteonecrosis group (84.7+/-5.5 microm) than in both the steroid-administered group (75.3+/-4.3 microm) and the normal group (76.3+/-4.9 microm) (p<0.01 and p<0.05, respectively). After adjusting for age and sex, the size of bone marrow fat cells in the early osteonecrosis group was significantly larger as compared with the other groups. This study suggests that in steroid-induced osteonecrosis, the size of bone marrow fat cells increases significantly at an early stage.

Adipocytes↗
PubMed2004

Roles of uroplakins in plaque formation, umbrella cell enlargement, and urinary tract diseases.

The apical surface of mouse urothelium is covered by two-dimensional crystals (plaques) of uroplakin (UP) particles. To study uroplakin function, we ablated the mouse UPII gene. A comparison of the phenotypes of UPII- and UPIII-deficient mice yielded new insights into the mechanism of plaque formation and some fundamental features of urothelial differentiation. Although UPIII knockout yielded small plaques, UPII knockout abolished plaque formation, indicating that both uroplakin heterodimers (UPIa/II and UPIb/III or IIIb) are required for plaque assembly. Both knockouts had elevated UPIb gene expression, suggesting that this is a general response to defective plaque assembly. Both knockouts also had small superficial cells, suggesting that continued fusion of uroplakin-delivering vesicles with the apical surface may contribute to umbrella cell enlargement. Both knockouts experienced vesicoureteral reflux, hydronephrosis, renal dysfunction, and, in the offspring of some breeding pairs, renal failure and neonatal death. These results highlight the functional importance of uroplakins and establish uroplakin defects as a possible cause of major urinary tract anomalies and death.

Animals↗
PubMed1992

The Expression Pattern of the Tonoplast Intrinsic Protein gamma-TIP in Arabidopsis thaliana Is Correlated with Cell Enlargement.

The vacuolar membrane (tonoplast) contains an abundant intrinsic protein with six membrane-spanning domains that is encoded by a small gene family. Different isoforms of tonoplast intrinsic protein (TIP) are expressed in different tissues or as a result of specific signals. Using promoter-beta-glucuronidase (GUS) fusions and in situ hybridization, we have examined the expression of gamma-TIP in Arabidopsis thaliana. GUS staining of plants transformed with promoter-GUS fusions showed that gamma-TIP gene expression is high in recently formed tissues of young roots. In the shoot, gamma-TIP gene expression was highest in the vascular bundles of stems and petioles, as well as in the stipules and in the receptacle of the flower. No GUS activity was detected in root or shoot meristems or in older tissues, suggesting temporal control of gamma-TIP gene expression associated with cell elongation and/or differentiation. In situ hybridization carried out with whole seedlings confirmed that in root tips, gamma-TIP mRNA was present only in the zone of cell elongation just behind the apical meristem. In seedling shoots, mRNA abundance was also found to be correlated with cell expansion. These results indicate that gamma-TIP may be expressed primarily at the time when the large central vacuoles are being formed during cell enlargement.

Journal Article↗
PubMed1998

Correlated long-term increase of brain-derived neurotrophic factor and Trk B proteins in enlarged granule cells of mouse hippocampus after kainic acid injection.

Our previous studies have shown that a single injection of kainic acid into the dorsal hippocampus of adult mice resulted in hypertrophy of the dentate gyrus granule cells. This hypertrophy was correlated with a long-lasting increase of brain-derived neurotrophic factor messenger RNA, and prevented by anti-sense brain-derived neurotrophic factor oligonucleotide treatment. These results suggest that an increase of brain-derived neurotrophic factor messenger RNA may be a major trigger of granule cells enlargement. However, the level of messenger RNA of Trk B, the high-affinity receptor of brain-derived neurotrophic factor, was not increased significantly, raising the question of whether increased brain-derived neurotrophic factor messenger RNA level leads actually to an increased protein production. The objective of the present study was to examine this; changes in contents of brain-derived neurotrophic factor and TrkB protein were monitored by immunohistochemistry during kainic acid-induced hypertrophy. Results show that immunoreactivities of brain-derived neurotrophic factor and Trk B were present in enlarged granule cells. These immunoreactivities increased from two to 16 weeks after kainic acid injection and were maintained up to 12 months. Simultaneous increases of brain-derived neurotrophic factor messenger RNA and protein, and of TrkB protein were coupled tightly to the chronology of granule cell enlargement, suggesting that the action of brain-derived neurotrophic factor in the induction and maintenance of kainic acid-induced granule cells enlargement is likely to be mediated by TrkB. The discrepancy between the previously described lack of increase of TrkB messenger RNA and the herein observed increase of the protein further reveals the existence of translational regulations of the receptor messenger RNA.

Animals↗
PubMed1999

Cell cycling and cell enlargement in developing leaves of Arabidopsis.

Cell cycling plays an important role in plant development, including: (1) organ morphogenesis, (2) cell proliferation within tissues, and (3) cell differentiation. In this study we use a cyclin::beta-glucuronidase reporter construct to characterize spatial and temporal patterns of cell cycling at each of these levels during wild-type development in the model genetic organism Arabidopsis thaliana (Columbia). We show that a key morphogenetic event in leaf development, blade formation, is highly correlated with localized cell cycling at the primordium margin. However, tissue layers are established by a more diffuse distribution of cycling cells that does not directly involve the marginal zone. During leaf expansion, tissue proliferation shows a strong longitudinal gradient, with basiplastic polarity. Tissue layers differ in pattern of proliferative cell divisions: cell cycling of palisade mesophyll precursors is prolonged in comparison to that of pavement cells of the adjacent epidermal layers, and cells exit the cycle at different characteristic sizes. Cell divisions directly related to formation of stomates and of vascular tissue from their respective precursors occur throughout the period of leaf extension, so that differing tissue patterns reflect superposition of cycling related to cell differentiation on more general tissue proliferation. Our results indicate that cell cycling related to leaf morphogenesis, tissue-specific patterns of cell proliferation, and cell differentiation occurs concurrently during leaf development and suggest that unique regulatory pathways may operate at each level.

Arabidopsis↗
PubMed1986

Effect of gamma radiation on resting B lymphocytes. I. Oxygen-dependent damage to the plasma membrane results in increased permeability and cell enlargement.

Although the susceptibility of resting B lymphocytes to radiation-induced interphase death is well known, the mechanism by which this occurs is not understood. In this report, we use three measures of plasma membrane integrity (increase in cell volume, uptake of trypan blue, and release of 51Cr) to assess the effect of radiation on the resting B cell plasma membrane. The delivery of 500 to 1000 rad caused the majority of resting B cells to enlarge slightly, whereas 3000 rad caused virtually all of the cells to approximately double in size within 3 to 4 hr. Measurement of the release of 51Cr from resting B cells revealed a similar relationship between the dose of radiation and the loss of radioactive label. Trypan blue exclusion was also found to diminish as a function of radiation dose. An analysis of a variety of lymphoid cells suggested that sensitivity to the membrane damaging effects of gamma radiation was in the order of resting B cells greater than resting T cells greater than a long-term L3T4+ T cell clone greater than a B cell lymphoma. LPS-induced B cell blasts treated with 3000 rad were equivalent to 1000 rad-treated resting B cells. The effects of the gamma radiation could be ameliorated by excluding oxygen (a diradical molecule that can potentially enhance the generation and propagation of highly reactive free radicals) at the time of irradiation, or by adding the free radical scavenging agent cysteamine. These data are compatible with the hypothesis that gamma radiation results in damage to the plasma membrane of resting lymphocytes via the generation of highly reactive free radical species. This damage is reflected in a rapid increase in plasma membrane permeability and swelling of the cells, and may play a major role in causing interphase death.

Animals↗