scholarly journals Myogenic protein expression before and after resistance loading in 26- and 64-yr-old men and women

2004 ◽  
Vol 97 (4) ◽  
pp. 1329-1337 ◽  
Author(s):  
Marcas M. Bamman ◽  
Ronald C. Ragan ◽  
Jeong-su Kim ◽  
James M. Cross ◽  
Vernishia J. Hill ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cyclin D1 ◽  
Muscle Biopsy ◽  
Repeated Measures ◽  
Kinase Inhibitor ◽  
Mechanical Load ◽  
Cyclin B1 ◽  
Inhibitory Influence ◽  
Vastus Lateralis Muscle ◽  
Cyclin Dependent Kinase

Based on the growing body of evidence implicating an important role for myogenic regulatory factors (MRFs) in the adaptive responses of skeletal muscle to mechanical load, we tested the hypothesis that protein concentrations of MRFs as well as cell cycle proteins (i.e., cyclins and cyclin-dependent kinase inhibitors) would be altered after heavy leg resistance exercise (RE). Because we and others, however, have shown a blunted adaptive response to long-term resistance training in older (O) women [females (F)] compared with men (M), we also tested the hypothesis that these myogenic responses to RE would be influenced by age and gender. Twenty-two younger (Y) adults (20–35 yr, 11 YF, 11 YM) and 20 O adults (60–75 yr, 9 OF, 11 OM) consented to vastus lateralis muscle biopsy before and 24 h after a bout of RE using a regimen known to induce myofiber hypertrophy when performed 2–3 days/wk for several weeks (3 sets of 80% one-repetition maximum for squat, leg press, and knee extension). Protein concentrations of MRFs (MyoD, myogenin, myf-6), cyclin D1, cyclin B1, α-actin, and the cyclin-dependent kinase inhibitor p27kip were determined by immunoblotting. Data were analyzed by using age × gender × load repeated-measures ANOVA. Myogenin expression was 44% higher ( P < 0.05) in O compared with Y, and myf-6 tended to be higher in OF compared with YF (95%, P = 0.059). A significant gender × load interaction indicated that, in F, RE led to a reduction in p27kip (20%; P < 0.05), which was driven mainly by a 27% drop in OF. Levels of cyclin D1, cyclin B1, MyoD, myf-6, and α-actin were not influenced by age, gender, or loading. We report a novel finding in humans of markedly higher myogenin protein content in older sedentary muscle. The results do not, however, support the hypothesis that myogenic protein expression is altered 24 h after RE, irrespective of age or gender. Although the time point of postexercise muscle biopsy could be viewed as too early to capture maximal effects for most of these proteins, the significant decline in p27kip concentration found in OF suggests that mechanical load may provide one means of overcoming the inhibitory influence of p27kip.

scholarly journals Frequency of polymorphisms and protein expression of cyclin-dependent kinase inhibitor 1A (CDKN1A) in central nervous system tumors

2009 ◽  
Vol 127 (5) ◽  
pp. 288-294 ◽  
Author(s):  
Mev Dominguez Valentin ◽  
Renata Canalle ◽  
Rosane de Paula Queiroz ◽  
Luiz Gonzaga Tone
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Protein Expression ◽  
Kinase Inhibitor ◽  
Expression Patterns ◽  
Cns Tumors ◽  
Control Group ◽  
Cyclin Dependent Kinase ◽  
Cross Sectional ◽  
Cyclin Dependent Kinase Inhibitor

CONTEXT AND OBJECTIVE: Genetic investigation of central nervous system (CNS) tumors provides valuable information about the genes regulating proliferation, differentiation, angiogenesis, migration and apoptosis in the CNS. The aim of our study was to determine the prevalence of genetic polymorphisms (codon 31 and 3' untranslated region, 3'UTR) and protein expression of the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene in patients with and without CNS tumors. DESIGN AND SETTING: Analytical cross-sectional study with a control group, at the Molecular Biology Laboratory, Pediatric Oncology Department, Hospital das Clínicas de Ribeirão Preto. METHODS: 41 patients with CNS tumors and a control group of 161 subjects without cancer and paires for sex, age and ethnicity were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Protein analysis was performed on 36 patients with CNS tumors, using the Western Blotting technique. RESULTS: The frequencies of the heterozygote (Ser/Arg) and polymorphic homozygote (Arg/Arg) genotypes of codon 31 in the control subjects were 28.0% and 1.2%, respectively. However, the 3'UTR site presented frequencies of 24.2% (C/T) and 0.6% (T/T). These frequencies were not statistically different (P > 0.05) from those seen in the patients with CNS tumors (19.4% and 0.0%, codon 31; 15.8% and 2.6%, 3'UTR site). Regarding the protein expression in ependymomas, 66.67% did not express the protein CDKN1A. The results for medulloblastomas and astrocytomas were similar: neither of them expressed the protein (57.14% and 61.54%, respectively). CONCLUSION: No significant differences in protein expression patterns or polymorphisms of CDKN1A in relation to the three types of CNS tumors were observed among Brazilian subjects.

scholarly journals Comparison of Acute Gene Expression Profiles of Islet Cells Obtained via Laser Capture Microdissection between Alloxan- and Streptozotocin-treated Rats

2018 ◽  
Vol 46 (6) ◽  
pp. 660-670 ◽  
Author(s):  
Yuki Kato ◽  
Yusaku Masago ◽  
Chiaki Kondo ◽  
Erika Yogo ◽  
Mikinori Torii ◽  
...  
Keyword(s):  
Gene Expression ◽  
Laser Capture Microdissection ◽  
Kinase Inhibitor ◽  
Expression Profiles ◽  
Cyclin B1 ◽  
Histopathological Analysis ◽  
G1 Arrest ◽  
Cyclin Dependent Kinase ◽  
Apoptotic Pathway ◽  
Laser Capture

To identify the molecular profiles of islets from alloxan (ALX)- and streptozotocin (STZ)-treated rats, a microarray-based global gene expression analysis was performed on frozen islets isolated via laser capture microdissection. At 6 weeks old, rats were injected with ALX (40 mg/kg) or STZ (50 or 100 mg/kg) and then euthanized 24 hr later. Histopathological analysis showed β-cell necrosis, macrophage infiltration, and islet atrophy. The extent of these changes was more notable in the STZ groups than in the ALX group. Transcriptome analysis demonstrated a significant up- or downregulation of cell cycle arrest–related genes in the p53 signaling pathway. Cyclin D2 and cyclin-dependent kinase inhibitor 1A, mediators of G1 arrest, were remarkably altered in STZ-treated rats. In contrast, cyclin-B1 and cyclin-dependent kinase 1, mediators of G2 arrest, were remarkably changed in ALX-treated rats. Genes involved in the intrinsic mitochondria-mediated apoptotic pathway were upregulated in the ALX and STZ groups. Moreover, heat-shock 70 kDA protein 1A ( Hspa1a), Hsp90ab1, and Hsph1 were upregulated in ALX-treated rats, suggesting that ALX treatment injures β cells via endoplasmic reticulum stress. These results contribute to a better understanding of gene expression in the pathogenesis of islet toxicity.

scholarly journals Differences in Protein Expression and Gene Amplification of Cyclins between Colon and Rectal Adenocarcinomas

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Rolf Aamodt ◽  
Kristin Jonsdottir ◽  
Solveig Norheim Andersen ◽  
Johan Bondi ◽  
Geir Bukholm ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cyclin D1 ◽  
Gene Amplification ◽  
Cyclin E ◽  
Cyclin B1 ◽  
University Hospital ◽  
Cyclin D3 ◽  
Colon Cancers ◽  
Rectal Cancers ◽  
Cyclin A2

Adenocarcinomas of rectum and colon may be different with regard to the cellular biological basis for cancer development. A material of 246 rectal cancers removed surgically at Akershus University Hospital in the years 1992–2000 was investigated and was compared to a material of 219 colon cancers operated on at Akershus University Hospital during the years 1988, 1990 and 1997–2000. There were highly significant differences between the rectal and the colon cancers in the protein expression of cyclin D1, cyclin D3, cyclin E, nuclearβ-catenin, and c-Myc and in gene amplification of cyclin A2, cyclin B1, cyclin D1, and cyclin E. Gene amplification and protein expression in the rectal cancers correlated significantly for the cyclins B1, D3, and E. A statistically significant relation was observed between overexpression of cyclin A2 and local relapse of rectal carcinomas, as higher expression of cyclin A2 was associated with lower local recurrence rate.

The Ubiquitin-Ligase APC-Cdh1 Is Required for Maintaining Genomic Stability and Is Transcriptional Repressed by AML1/ETO.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1609-1609
Author(s):  
Ralph Waesch ◽  
Dirk Engelbert ◽  
Dominik Schnerch
Keyword(s):  
Ubiquitin Ligase ◽  
Transcriptional Repression ◽  
Genetic Instability ◽  
Kinase Inhibitor ◽  
Cell Cycle Control ◽  
Genomic Stability ◽  
Cyclin B1 ◽  
Cyclin Dependent Kinase ◽  
Anaphase Promoting Complex ◽  
Cyclin Dependent Kinase Inhibitor

Abstract Accurate DNA replication and chromosome segregation is essential during cell division in order to provide genomic stability and avoid malignant growth. We found that ubiquitin-dependent proteolytic cell cycle control by the E3-ubiquitin-ligase anaphase-promoting complex (APC) activated by Cdh1 (APC-Cdh1) is required for maintaining genomic integrity and viability in proliferating human cells. Lentiviral-delivered stable expression of short hairpins targeted against Cdh1 causes an apoptotic phenotype associated with p53-stabilization and p53-dependent transcriptional up-regulation of the cyclin-dependent kinase inhibitor p21. Cdh1-depleted cells enter mitosis delayed compared to controls suggesting the activation of a DNA-damage checkpoint in S- and G2-phase. Depletion of Cdh1 leads to premature accumulation of cyclin A2 and cyclin B1 in G1- and S-phase. This may interfere with loading of pre-replication-complexes onto origins of replication in G1 and cause chromosomal instability when cells progress into mitosis. In addition, stabilization of the Cdh1 target Aurora A at physiological levels is sufficient to cause centrosome overduplication and subsequent polyploidization in Cdh1 and p53 deficient cells. Genetic instability is a hallmark of cancer cells and deregulation of APC-Cdh1 may be involved, since we observe downregulation of Cdh1 in t(8;21) acute myeloid leukemia. Moreover, expression of AML1/ETO in an inducible system leads to downregulation of Cdh1 indicating transcriptional repression of Cdh1 by AML1/ETO. Consistent with these data AML1/ETO positive cell lines show numerical chromosomal aberrations. Thus, disruption of the central mitotic control machinery leads to genetic instability by several mechanisms and the APC may be an important suppressor of tumor progression in AML1/ETO positive leukemia.

scholarly journals MIB-1 (KI-67) Proliferation Index and Cyclin-Dependent Kinase Inhibitor p27Kip1 Protein Expression in Nephroblastoma

2004 ◽  
Vol 10 (2) ◽  
pp. 591-597 ◽  
Author(s):  
Mazen A. Ghanem ◽  
Theo H. Van der Kwast ◽  
Mondastri K. Sudaryo ◽  
Rejiv B. Mathoera ◽  
Marry M. van den Heuvel ◽  
...  
Keyword(s):  
Protein Expression ◽  
Kinase Inhibitor ◽  
Proliferation Index ◽  
Cyclin Dependent Kinase ◽  
Ki 67 ◽  
P27kip1 Protein ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Mib 1

Application of Proteomics in the Search for Novel Proteins Associated with the Anti-cancer Effect of the Synthetic Cyclin-dependent Kinases Inhibitor, Bohemine

2002 ◽  
Vol 1 (4) ◽  
pp. 247-256 ◽  
Author(s):  
Hana Kovarova ◽  
Petr Halada ◽  
Petr Man ◽  
Petr Dzubak ◽  
Marian Hajduch
Keyword(s):  
Mass Spectrometry ◽  
Cell Cycle ◽  
Protein Expression ◽  
Cell Line ◽  
Metabolic Pathways ◽  
Kinase Inhibitor ◽  
A549 Cells ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Anti Cancer

The purpose of this study was to use the proteomics approach, which is based on high resolution two-dimensional electrophoresis coupled with multivariate correspondence analysis and mass spectrometry, to classify objectively the biochemical basis of the anti-cancer activity of the synthetic cyclin-dependent kinase inhibitor, bohemine (BOH). The changes in the cell cycle and corresponding protein composition of the A549 human lung adenocarcinoma cell line after treatment with BOH were evaluated and proteins differentially expressed in the BOH treated A549 cells, compared to the untreated A549 counterparts, were selected. Thirteen of these candidate proteins associated with the drug effects in vitro were identified by mass spectrometry. Many of these proteins fall into one of three functional categories: i) metabolic pathways (glycolysis, nucleic acid synthesis and NADPH production), ii) stress response and protein folding, and iii) cytoskeleton and exocytosis. Changes in protein expression patterns corresponded to a higher resistance of A549 lung carcinoma cells to BOH when compared to the CEM leukaemia cell line. These protein changes reflect a fine balance of the resistant versus the susceptible phenotype in response to the drug. Since BOH is a selective cyclin-dependent kinase inhibitor, changes in the protein expression pattern can be more generally associated with cell cycle regulation as evidenced by inhibition of cell cycling in A549 cells. Our conclusions further underline the importance of cell cycle control in both the cellular signalling and metabolic pathways.

scholarly journals Anti-Cancer Potential of Oxialis obtriangulata in Pancreatic Cancer Cell through Regulation of the ERK/Src/STAT3-Mediated Pathway

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2301 ◽  
Author(s):  
Eun-Jin An ◽  
Yumi Kim ◽  
Seung-Hyeon Lee ◽  
Hyun Min Ko ◽  
Won-Seok Chung ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Kinase Inhibitor ◽  
Cyclin B1 ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Plant Medicine ◽  
Anti Cancer ◽  
M Phase

As a plant medicine, Oxalidaceae has been used to treat various diseases in Korea. However, there is little data on the anti-cancer efficacy of Oxalidaceae, particularly O. obtriangulata. This study aimed to investigate the anti-cancer effect of O. obtriangulata methanol extract (OOE) and its regulatory actions on pancreatic carcinoma. OOE showed anti-proliferative effects and induced cell death in the colony formation and cell viability assays, respectively. The Fluorescence-activated cell sorting (FACS) data confirmed that OOE significantly induced cell cycle accumulation at the G2/M phase and apoptotic effects. Additionally, OOE inhibited the activated ERK (extracellular-signal-regulated kinase)/Src (Proto-oncogene tyrosine-protein kinase Src)/STAT3 (signal transducers and activators of transcription 3) pathways including nuclear translocation of STAT3. Furthermore, suppression of Ki67, PARP(Poly ADP-ribose polymerase), caspase-3, P27(Cyclin-dependent kinase inhibitor 1B), and c-Myc as well as the STAT3 target genes CDK(cyclin-dependent kinase)1, CDK2, Cyclin B1, VEGF-1(vascular endothelial growth factor-1), MMP-9(Matrix metallopeptidase 9), and Survivin by OOE was observed in BxPC3. We speculate that these molecular actions might support an anti-cancer effect of OOE. In this study, we demonstrated that OOE may be a promising anti-cancer material and may serve as a natural therapy and alternative remedy for pancreatic cancer treatment.

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