scholarly journals Cadmium Impairs p53 Activity in HepG2 Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
C. Urani ◽  
P. Melchioretto ◽  
M. Fabbri ◽  
G. Bowe ◽  
E. Maserati ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Conformational Changes ◽  
Protein Level ◽  
Cell Cycle Progression ◽  
Hepatoma Cell ◽  
Hepatoma Cell Line ◽  
Cycle Arrest ◽  
Promote Cell Cycle Progression ◽  
Cycle Regulation ◽  
P53 Network

Cadmium and cadmium compounds are contaminants of the environment, food, and drinking water and are important constituents of cigarette smoke. Cd exposure has also been associated with airborne particulate CdO and with Cd-containing quantum dots in medical therapy. Adverse cadmium effects reported in the literature have stimulated during recent years an ongoing discussion to better elucidate cadmium outcomes at cell and molecular level. The present work is designed to gain an insight into the mechanism of p53 impairment at gene and protein level to understand Cd-induced resistance to apoptosis. We used a hepatoma cell line (HepG2) derived from liver, known to be metal responsive. At genotoxic cadmium concentrations no cell cycle arrest was observed. The p53 at gene and protein level was not regulated. Fluorescence images showed that p53 was correctly translocated into the nucleus but that the p21Cip1/WAF-1, a downstream protein of p53 network involved in cell cycle regulation, was not activated at the highest cadmium concentrations used. The miRNAs analysis revealed an upregulation of mir-372, an miRNA able to affect p21Cip1/WAF-1 expression and promote cell cycle progression and proliferation. The role of metallothioneins and possible conformational changes of p53 are discussed.

Abstract W P198: Sphingomyelin Synthases Regulate Neuronal Cell Proliferation and Cell Cycle Progression

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Umadevi V Wesley ◽  
Daniel Tremmel ◽  
Robert Dempsey
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Neuronal Cell ◽  
Artery Occlusion ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
Cycle Regulation ◽  
Cerebral Artery Occlusion

Introduction: The molecular mechanisms of cerebral ischemia damage and protection are not completely understood, but a number of reports implicate the contribution of lipid metabolism and cell-cycle regulating proteins in stroke out come. We have previously shown that tricyclodecan-9-yl-xanthogenate (D609) resulted in increased ceramide levels after transient middle cerebral artery occlusion (tMCAO) in spontaneously hypertensive rat (SHR). We hypothesized that D609 induced cell cycle arrest probably by inhibiting sphingomyelin synthase (SMS). In this study, we examined the direct effects of SMS on cell cycle progression and proliferation of neuroblast cells. Methods: Ischemia was induced by middle cerebral artery occlusion (MCAO) and reperfusion. Expression levels were measured by western blot analysis, RT-PCR, and Immunofluorescence staining. SMS1 and 2 expressions were silenced by stable transfection with SMS1/2-targeted shRNA. Cell cycle analysis was performed using Flow cytometry. Data were analyzed using MODFIT cell cycle analysis program. Cell proliferation rate was measured by MTT assay. Results: We have identified that the expression of SMS1is significantly up-regulated in the ischemic hemisphere following MCAO. Neuro-2a cells transfected with SMS specific ShRNA acquired more neuronal like phenotype and exhibited decreased proliferation rate. Also, silencing of both SMS1 and 2 induced cell-cycle arrest as shown by significantly increased percentage of cells in G0/G1 and decreased proportion of cells in S-phase as compared to control cells. This was accompanied by up-regulation of cyclin-dependent kinase (Cdk) inhibitors p21 and decreased levels of phophorylated AKT levels. Furthermore, loss of SMS inhibited the migratory potential of Neuro 2a cells. Summary: Up-regulation of SMS under ischemic/reperfusion conditions suggests that this enzyme potentially contributes to cell cycle regulation and may contribute to maintaining neuronal cell population. Further studies may open up a new direction for identifying the molecular mechanisms of cell cycle regulation and protection following ischemic stroke

scholarly journals A role for ATP Citrate Lyase in cell cycle regulation during myeloid differentiation

2019 ◽  
Author(s):  
Jess Rhee ◽  
Lauren A. Solomon ◽  
Rodney P. DeKoter
Keyword(s):  
Cell Cycle ◽  
Fatty Acid ◽  
Cell Cycle Regulation ◽  
Cell Cycle Progression ◽  
Acid Synthesis ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Cycle Arrest ◽  
Citrate Lyase ◽  
Cycle Regulation

AbstractDifferentiation of myeloid progenitor cells into macrophages is accompanied by increased PU.1 concentration and increasing cell cycle length, culminating in cell cycle arrest. Induction of PU.1 expression in a cultured myeloid cell line expressing low PU.1 concentration results in decreased levels of mRNA encoding ATP-Citrate Lyase (ACL) and cell cycle arrest. ACL is an essential enzyme for generating acetyl-CoA, a key metabolite for the first step in fatty acid synthesis as well as for histone acetylation. We hypothesized that ACL may play a role in cell cycle regulation in the myeloid lineage. In this study, we found that acetyl-CoA or acetate supplementation was sufficient to rescue cell cycle progression in cultured BN cells treated with an ACL inhibitor or induced for PU.1 expression. Acetyl-CoA supplementation was also sufficient to rescue cell cycle progression in BN cells treated with a fatty acid synthase (FASN) inhibitor. We demonstrated that acetyl-CoA was utilized in both fatty acid synthesis and histone acetylation pathways to promote proliferation. Finally, we found that Acly mRNA transcript levels decrease during normal macrophage differentiation from bone marrow precursors. Our results suggest that regulation of ACL activity is a potentially important point of control for cell cycle regulation in the myeloid lineage.

scholarly journals Human Eukaryotic Release Factor 3a Depletion Causes Cell Cycle Arrest at G1 Phase through Inhibition of the mTOR Pathway

2007 ◽  
Vol 27 (16) ◽  
pp. 5619-5629 ◽  
Author(s):  
Céline Chauvin ◽  
Samia Salhi ◽  
Olivier Jean-Jean
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Translation Termination ◽  
Binding Activity ◽  
Release Factor ◽  
Translation Rate ◽  
Cytoskeleton Organization ◽  
Cycle Arrest ◽  
Cycle Regulation ◽  
Mtor Activity

ABSTRACT Eukaryotic release factor 3 (eRF3) is a GTPase associated with eRF1 in a complex that mediates translation termination in eukaryotes. Studies have related eRF3 with cell cycle regulation, cytoskeleton organization, and tumorigenesis. In mammals, two genes encode two distinct forms of eRF3, eRF3a and eRF3b, which differ in their N-terminal domains. eRF3a is the major factor acting in translation termination, and its expression level controls termination complex formation. Here, we investigate the role of eRF3a in cell cycle progression using short interfering RNAs and flow cytometry. We show that eRF3a depletion induces a G1 arrest and that eRF3a GTP-binding activity, but not the eRF3a N-terminal domain, is required to restore G1-to-S-phase progression. We also show that eRF3a depletion decreases the global translation rate and reduces the polysome charge of mRNA. Finally, we show that two substrates of the mammalian TOR (mTOR) kinase, 4E-BP1 and protein kinase S6K1, are hypophosphorylated in eRF3a-depleted cells. These results strongly suggest that the G1 arrest and the decrease in translation induced by eRF3a depletion are due to the inhibition of mTOR activity and hence that eRF3a belongs to the regulatory pathway of mTOR activity.

scholarly journals Selenium supplementation protects against oxidative stress-induced cardiomyocyte cell cycle arrest through activation of PI3K/AKT

Metallomics ◽  
2020 ◽  
Author(s):  
Wenjuan Sun ◽  
Jiawei Zhu ◽  
Shuang Li ◽  
Chaohua Tang ◽  
Qingyu Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Cycle Progression ◽  
Inhibitory System ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
System P ◽  
M Phase ◽  
Promote Cell Cycle Progression

Selenium alleviates oxidative stress-induced cell cycle arrest in cardiomyocytes mediated by antioxidant capacity of selenoproteins, thus activating PI3K/AKT pathways, which promote cell cycle progression by targeting the G2/M phase inhibitory system.

scholarly journals p16INK4A-independence of Epstein–Barr virus-induced cell proliferation and virus latency

2004 ◽  
Vol 85 (6) ◽  
pp. 1381-1386 ◽  
Author(s):  
Michelle J. Hayes ◽  
Anna Koundouris ◽  
Nelleke Gruis ◽  
Wilma Bergman ◽  
Gordon G. Peters ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Epstein Barr Virus ◽  
Cell Cycle Progression ◽  
Restriction Point ◽  
Barr Virus ◽  
Virus Latency ◽  
Cycle Arrest ◽  
Direct Binding ◽  
Promote Cell Cycle Progression ◽  
Epstein Barr

Epstein–Barr virus (EBV) has the ability to promote cell cycle progression following the initial infection of primary resting B-lymphocytes and to cause cell cycle arrest at the onset of the viral replicative cycle. Various mechanisms have been proposed for the proliferative effects, including the up-regulation of cyclin D2 by the viral EBNA-2 and EBNA-LP proteins, direct binding of EBNA3C to the retinoblastoma protein (pRb), and down-regulation of the p16INK4A tumour suppressor by the viral LMP1 product. To try to gain insight into the relative importance of these mechanisms, the ability of EBV to immortalize lymphocytes from an individual who is genetically deficient for p16INK4A was examined. From detailed analyses of the resultant lymphoblastoid cell lines it is concluded that p16INK4A status has little bearing on EBV's ability to manipulate the cell cycle machinery and a model to accommodate the previously proposed routes taken by EBV to bypass the restriction point is presented.

Expression profiles of miRNAs and involvement of miR-100 and miR-34 in regulation of cell cycle arrest in Artemia

2015 ◽  
Vol 470 (2) ◽  
pp. 223-231 ◽  
Author(s):  
Ling-Ling Zhao ◽  
Feng Jin ◽  
Xiang Ye ◽  
Lin Zhu ◽  
Jin-Shu Yang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Cycle Regulation ◽  
Cell Cycle Progression ◽  
Expression Profiles ◽  
Regulatory Mechanisms ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
Regulation Of Cell Cycle ◽  
Cycle Regulation

We established an expression profile of miRNA for cell cycle arrest in Artemia and found that miR-100 and miR-34 promote and prevent cell cycle progression respectively. The regulatory mechanisms of these two miRNAs provide insights into cell cycle regulation.

scholarly journals Inhibition of G2/M progression in Schizosaccharomyces pombe by a mutant calmodulin kinase II with constitutive activity.

1994 ◽  
Vol 5 (7) ◽  
pp. 785-795 ◽  
Author(s):  
C Rasmussen ◽  
G Rasmussen
Keyword(s):  
Cell Cycle ◽  
Schizosaccharomyces Pombe ◽  
Intracellular Signaling ◽  
Cell Cycle Progression ◽  
Cell Function ◽  
Cycle Arrest ◽  
Calmodulin Kinase ◽  
Cycle Regulation ◽  
Kinase Expression ◽  
P34 Cdc2

Intracellular signaling by the second messenger Ca2+ through its receptor calmodulin (CaM) regulates cell function via the activation of CaM-dependent enzymes. Previous studies have shown that cell cycle progression at G1/S and G2/M is sensitive to intracellular CaM levels. However, little is known about the CaM-regulated enzymes involved. Protein phosphorylation has been shown to be important for cell-cycle regulation. Because CaM regulates several protein kinases, and at least one protein phosphatase, our studies are focusing on the roles of these enzymes within the cell cycle. As an initial approach to this problem, cDNAs encoding either normal or mutant calcium/calmodulin kinase II (CaMKII) have been expressed in Schizosaccharomyces pombe. The results show that overexpression of a constitutively active mutant CaMKII caused cell-cycle arrest in G2. Arrest was associated with a failure to activate the p34/cdc2 protein kinase. Expression of the mutant CaMKII in strains of S. pombe with altered timing of mitosis revealed that this effect is not mediated either by cdc25+ or wee1+, suggesting that CaMKII may regulate G2/M progression by another mechanism.

scholarly journals Histone Deacetylase 10 Regulates the Cell Cycle G2/M Phase Transition via a Novel Let-7–HMGA2–Cyclin A2 Pathway

2015 ◽  
Vol 35 (20) ◽  
pp. 3547-3565 ◽  
Author(s):  
Yixuan Li ◽  
Lirong Peng ◽  
Edward Seto
Keyword(s):  
Cell Cycle ◽  
Histone Deacetylase ◽  
Cell Cycle Progression ◽  
Transcriptional Repressors ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
M Phase ◽  
Cyclin A2 ◽  
Cell Growth And Proliferation ◽  
Cycle Regulation

Histone deacetylase (HDAC) inhibition leads to cell cycle arrest in G1and G2, suggesting HDACs as therapeutic targets for cancer and diseases linked to abnormal cell growth and proliferation. Many HDACs are transcriptional repressors. Some may alter cell cycle progression by deacetylating histones and repressing transcription of key cell cycle regulatory genes. Here, we report that HDAC10 regulates the cell cycle via modulation of cyclin A2 expression, and cyclin A2 overexpression rescues HDAC10 knockdown-induced G2/M transition arrest. HDAC10 regulates cyclin A2 expression by deacetylating histones near thelet-7promoter, thereby repressing transcription. InHDAC10knockdown cells,let-7fand microRNA 98 (miR-98) were upregulated and thelet-7family target,HMGA2, was downregulated. HMGA2 loss resulted in enrichment of the transcriptional repressor E4F at the cyclin A2 promoter. These findings support a role for HDACs in cell cycle regulation, reveal a novel mechanism of HDAC10 action, and extend the potential of HDACs as targets in diseases of cell cycle dysregulation.

Sign in / Sign up

Export Citation Format

Share Document