scholarly journals Natural variation in the histone demethylase, KDM4C, influences expression levels of specific genes including those that affect cell growth

2013 ◽  
Vol 24 (1) ◽  
pp. 52-63 ◽  
Author(s):  
B. L. Gregory ◽  
V. G. Cheung
Keyword(s):  
Cell Growth ◽  
Natural Variation ◽  
Histone Demethylase ◽  
Expression Levels ◽  
Affect Cell Growth

scholarly journals Prohibitins Regulate Membrane Protein Degradation by the m-AAA Protease in Mitochondria

1999 ◽  
Vol 19 (5) ◽  
pp. 3435-3442 ◽  
Author(s):  
Gregor Steglich ◽  
Walter Neupert ◽  
Thomas Langer
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Growth ◽  
Membrane Proteins ◽  
Eukaryotic Cells ◽  
Mitochondrial Morphology ◽  
Regulatory Effect ◽  
Inner Membrane ◽  
Functional Activities ◽  
Native Molecular Mass ◽  
Affect Cell Growth

ABSTRACT Prohibitins comprise a protein family in eukaryotic cells with potential roles in senescence and tumor suppression. Phb1p and Phb2p, members of the prohibitin family in Saccharomyces cerevisiae, have been implicated in the regulation of the replicative life span of the cells and in the maintenance of mitochondrial morphology. The functional activities of these proteins, however, have not been elucidated. We demonstrate here that prohibitins regulate the turnover of membrane proteins by the m-AAA protease, a conserved ATP-dependent protease in the inner membrane of mitochondria. The m-AAA protease is composed of the homologous subunits Yta10p (Afg3p) and Yta12p (Rca1p). Deletion ofPHB1 or PHB2 impairs growth of Δyta10 or Δyta12 cells but does not affect cell growth in the presence of the m-AAA protease. A prohibitin complex with a native molecular mass of approximately 2 MDa containing Phb1p and Phb2p forms a supercomplex with them-AAA protease. Proteolysis of nonassembled inner membrane proteins by the m-AAA protease is accelerated in mitochondria lacking Phb1p or Phb2p, indicating a negative regulatory effect of prohibitins on m-AAA protease activity. These results functionally link members of two conserved protein families in eukaryotes to the degradation of membrane proteins in mitochondria.

How Plant Hormones and Their Interactions Affect Cell Growth

2016 ◽  
pp. 174-195 ◽  
Author(s):  
Stephen Depuydt ◽  
Stan Van Praet ◽  
Hilde Nelissen ◽  
Bartel Vanholme ◽  
Danny Vereecke
Keyword(s):  
Cell Growth ◽  
Plant Hormones ◽  
Affect Cell Growth

190 SUPPRESSION OF A TRANSCRIPTION FACTOR MSX1 GENE IN BOVINE PREIMPLANTATION EMBRYOS AND ITS EFFECT ON mRNA, PROTEIN, AND EXPRESSION OF DOWNSTREAM GENES

2008 ◽  
Vol 20 (1) ◽  
pp. 174
Author(s):  
D. Tesfaye ◽  
A. Regassa ◽  
M. Hoelker ◽  
F. Rings ◽  
C. Phatsara ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Growth ◽  
Protein Expression ◽  
Cdna Array ◽  
Blastocyst Stage ◽  
Preimplantation Embryos ◽  
Bovine Embryos ◽  
Expression Levels ◽  
Treatment Groups ◽  
Zygote Stage

MSX1 is a transcription factor gene that orchestrates gene expression and regulates cell growth, proliferation, differentiation, cell-to-cell communication, and the apoptotic pathway during pattern formation in vertebrate embryogenesis. However, its role in bovine preimplantation embryo is not known. Here we aim to investigate the effects of suppressing MSX1 transcript on the development of in vitro-produced bovine embryos, study the expression of mRNA and protein products of the gene, and identify downstream genes using microarray analysis. In the first experiment, IVP zygotes were injected with 341 bp-long dsRNA (LdsRNA) (n = 384), 19 bp small interfering RNA (siRNA) (n = 374), and scrambled sequence RNA (scRNA) (n = 388). Uninjected zygotes (n = 313) were used as control. Developmental phenotype data were collected during culture until Day 8. The mRNA and protein expression levels of the different treatment groups were validated at the 8-cell and blastocyst stages using quantitative real-time PCR and immunohistochemistry, respectively. Developmental phenotype and mRNA data were analyzed using ANOVA under statistical package SPSS (SPSS, Inc., Chicago, IL, USA). In the second experiment, custom SMARTpool siRNA (Dharmacon Inc., Chicago, IL, USA) targeting bovine MSX1 (NM_174798) was used for microinjection together with siRNA and uninjected control. Following treatment at zygote stage, 8-cell embryos were used for mRNA isolation and subsequent array hybridization using bovine cDNA array containing 2000 clones. Array data analysis was performed using statistical analysis of microarray (SAM) procedure. While 33% and 29% of the zygotes from the control and scRNA treatment groups, respectively, reached blastocyst stage, only 20% and 19% of the zygotes from the LdsRNA and siRNA treatment groups, respectively, reached the same stage. Injection of LdsRNA and siRNA at the zygote stage reduced the mRNA expression level by 52% and 33% at the 8-cell stage and by 77% and 87%, respectively, at the blastocyst stage as compared to the control. Similarly, cellular protein expression levels in LdsRNA- and siRNA-injected treatment groups were found to be lower than the control groups at each stage. In all cases, injection of scRNA had no effect on mRNA and protein levels. SAM analysis revealed that, of the total 2000 clones, 3.5% and 5.4% were found to be differentially expressed in embryos injected with SMARTpool and siRNA, respectively, compared to the control. Genes involved in various activities including transcription factors (ALF), cell growth (BMP-15), metabolism (RIOK3), and cytokinasis (AURKA) were found to be down-regulated in 8-cell embryos treated with SMARTpool siRNA compared to the controls. On the other hand, genes involved in protein synthesis (RPL23), energy metabolism (COQ1), cell growth (MNS1) and skeletal development (LGALS3) were found to be upregulated in the same samples. In conclusion, suppression of MSX1 at the mRNA and protein level significantly affected the development of bovine embryos, and our study revealed list of downstream genes regulated by the activity of MSX1.

scholarly journals Flavored e-liquids increase cytoplasmic Ca2+ levels in airway epithelia

2020 ◽  
Vol 318 (2) ◽  
pp. L226-L241 ◽  
Author(s):  
Temperance R. Rowell ◽  
James E. Keating ◽  
Bryan T. Zorn ◽  
Gary L. Glish ◽  
Stephen B. Shears ◽  
...  
Keyword(s):  
Cell Growth ◽  
Biological Effects ◽  
Potential Toxicity ◽  
Airway Epithelia ◽  
Unknown Mechanism ◽  
Kinase C ◽  
Short And Long Term ◽  
Cellular Ca ◽  
Affect Cell Growth

E-cigarettes are noncombustible, electronic nicotine-delivery devices that aerosolize an e-liquid, i.e., nicotine, in a propylene glycol-vegetable glycerin vehicle that also contains flavors. While the effects of nicotine are relatively well understood, more information regarding the potential biological effects of the other e-liquid constituents is needed. This is a serious concern, because e-liquids are available in >7,000 distinct flavors. We previously demonstrated that many e-liquids affect cell growth/viability through an unknown mechanism. Since Ca2+ is a ubiquitous second messenger that regulates cell growth, we characterized the effects of e-liquids on cellular Ca2+ homeostasis. To better understand the extent of this effect, we screened e-liquids for their ability to alter cytosolic Ca2+ levels and found that 42 of 100 flavored e-liquids elicited a cellular Ca2+ response. Banana Pudding (BP) e-liquid, a representative e-liquid from this group, caused phospholipase C activation, endoplasmic reticulum (ER) Ca2+ release, store-operated Ca2+ entry (SOCE), and protein kinase C (PKCα) phosphorylation. However, longer exposures to BP e-liquid depleted ER Ca2+ stores and inhibited SOCE, suggesting that this e-liquid may alter Ca2+ homeostasis by short- and long-term mechanisms. Since dysregulation of Ca2+ signaling can cause chronic inflammation, ER stress, and abnormal cell growth, flavored e-cigarette products that can elicit cell Ca2+ responses should be further screened for potential toxicity.

PU.1 Is Downregulated in a Subset of Multiple Myeloma by the Methylation of Its -17 kb Upstream Regulatory Region and the Promoter.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3417-3417
Author(s):  
Yutaka Okuno ◽  
Hiro Tatetsu ◽  
Shikiko Ueno ◽  
Hiroyuki Hata ◽  
Yasuhiro Yamada ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Growth ◽  
Cell Lines ◽  
Promoter Region ◽  
Growth Arrest ◽  
Myeloma Cell ◽  
Upstream Region ◽  
Cell Growth Arrest ◽  
Myeloma Cells ◽  
Expression Levels

Abstract It has been reported that disruption of transcription factors critical for hematopoiesis, such as C/EBPa and AML1, is involved in leukemogenesis. PU.1 is a transcription factor important for both myeloid and lymphoid development. We reported that mice in which the levels of PU.1 were 20% of that of wild-type developed acute myeloid leukemia, T cell lymphoma, and a CLL-like disease. These findings strongly suggest that PU.1 has tumor suppressive activity in multiple hematopoietic lineages. Last year, we reported that PU.1 is downregulated in a majority of multiple myeloma cell lines and and freshly isolated CD138 positive myeloma cells from certain number of myeloma patients, and that tet-off inducible exogenous expression of PU.1 in PU.1 negative myeloma cell lines induced cell growth arrest and apoptosis. Based on their PU.1 expression levels, we divided the myeloma patients into two groups, namely PU.1 high and PU.1 low-to-negative, (cutoff index of 25th percentile of the PU.1 expression level distribution among all patients). The PU.1 low-to-negative patients had a significantly poorer prognosis than the PU.1 high patients. To elucidate the mechanisms of downregulation of PU.1, we performed sequence and epigenetic analysis of the promoter region and the -17 kb upstream region that is conserved among mammalians and important for proper expression of PU.1. There are no mutations in these regions of all five myeloma cell lines. In contrast, the -17 kb upstream region was highly methylated in 3 of 4 PU.1 negative myeloma cell lines, while the promoter region was also methylated to various levels in all five myeloma cell lines including one PU.1 positive cell line. These data suggested that the downregulation of PU.1 in myeloma cell lines might be dependent on the methylation of both regulatory regions of PU.1 gene, especially the -17 kb upstream region. We also evaluated the mechanisms of cell growth arrest and apoptosis of myeloma cell lines induced by PU.1. Among apoptosis-related genes, we identified that TRAIL was upregulated after PU.1 induction. To evaluate the effect of upregulation of TRAIL, we stably introduced siRNA for TRAIL into myeloma cell lines expressing PU.1, and we found that apoptosis of these cells was partially suppressed by siRNA for TRAIL, suggesting that apoptosis of myeloma cells induced by PU.1 might be at least partially due to TRAIL upregulation. We are currently performing DNA microarray analysis to compare the expression levels of genes between before and after PU.1 induction, in order to further elucidate the mechanisms of cell growth arrest and apoptosis.

scholarly journals Concerning the localization of steroids in centrioles and basal bodies by immunofluorescence.

1978 ◽  
Vol 76 (2) ◽  
pp. 255-260 ◽  
Author(s):  
I Nenci ◽  
E Marchetti
Keyword(s):  
Cell Growth ◽  
Basal Bodies ◽  
Immunofluorescence Technique ◽  
Cell Growth And Differentiation ◽  
Affect Cell Growth

Specific steroid antibodies, by the immunofluorescence technique, regularly reveal fluorescent centrioles and cilia-bearing basal bodies in target and nontarget cells. Although the precise identity of the immunoreactive steroid substance has not yet been established, it seems noteworthy that exogenous steroids can be vitally concentrated by centrioles, perhaps by exchange with steroids already present at this level. This unexpected localization suggests that steroids may affect cell growth and differentiation in some way different from the two-step receptor mechanism.

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