scholarly journals Vitamin D regulation of a SOD1-to-SOD2 antioxidative switch to prevent osteosarcoma transformation

2020 ◽  
Author(s):  
Thomas S. Lisse
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Proliferating Cell Nuclear Antigen ◽  
Fold Increase ◽  
Nuclear Antigen ◽  
Pcr Analysis ◽  
Oxygen Species ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Complex Iv ◽  
Proliferating Cell

AbstractSuperoxide, a form of reactive oxygen species (ROS), is catabolized by superoxide dismutase (SOD) and contributes to carcinogenesis via the oxidative damage it inflicts on cells. The aim of this research was to analyze the potential vitamin D-mediated regulation of the antioxidative “SOD1-to-SOD2 switch” within the human MG-63 osteosarcoma model. For this study, real-time PCR analysis was performed using MG-63 cells exposed to metabolically active 1,25(OH)2D3. Frist, a sustained statistically significant >2-fold suppression of proliferating cell nuclear antigen (PCNA) transcripts was observed after 10nM but not at 100nM of 1,25(OH)2D3 treatment, suggesting a cytostatic effect. In order to assess regulators of mitochondrial oxidative phosphorylation, gene expression of COX2 and COX4l1 of the mitochondrial complex IV and antioxidative enzymes (SOD1, SOD2 and Catalase (CAT)) were monitored. For COX2 and COX4l1, no changes in gene expression were observed. However, a concomitant decrease in CAT and SOD1 mRNA, and increase in SOD2 mRNA after 24 hours of 10nM 1,25(OH)2D3 treatment were observed. A ~8-fold increase in SOD2 mRNA was apparent after 48 hours. The significant increase in SOD2 activity in the presence of vitamin D indicates an antioxidant potential and sensitization of vitamin D during osteosarcoma transformation and mitochondrial detoxification over time.

scholarly journals Vitamin D Regulation of a SOD1-to-SOD2 Antioxidative Switch to Prevent Osteosarcoma Transformation

2020 ◽  
Author(s):  
Thomas S. Lisse
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Proliferating Cell Nuclear Antigen ◽  
Fold Increase ◽  
Nuclear Antigen ◽  
Pcr Analysis ◽  
Oxygen Species ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Complex Iv ◽  
Proliferating Cell

Superoxide, a form of reactive oxygen species (ROS), is catabolized by superoxide dismutase (SOD) and contributes to carcinogenesis via the oxidative damage it inflicts on cells. The aim of this research was to analyze the potential vitamin D-mediated regulation of the antioxidative “SOD1-to-SOD2 switch” within the human MG-63 osteosarcoma model. For this study; real-time PCR analysis was performed using MG-63 cells exposed to metabolically active 1,25(OH)2D3. Frist; a sustained statistically significant >2-fold suppression of proliferating cell nuclear antigen (PCNA) transcripts was observed after 10nM but not at 100nM of 1,25(OH)2D3 treatment; suggesting a cytostatic effect. In order to assess regulators of mitochondrial oxidative phosphorylation; gene expression of COX2 and COX4l1 of the mitochondrial complex IV and antioxidative enzymes (SOD1; SOD2 and Catalase (CAT)) were monitored. For COX2 and COX4l1; no changes in gene expression were observed. However; a concomitant decrease in CAT and SOD1 mRNA; and increase in SOD2 mRNA after 24 hours of 10nM 1,25(OH)2D3 treatment were observed. A ~8-fold increase in SOD2 mRNA was apparent after 48 hours. The significant increase in SOD2 activity in the presence of vitamin D indicates an antioxidant potential and sensitization of vitamin D during osteosarcoma transformation and mitochondrial detoxification over time.

scholarly journals Vitamin D Regulation of a SOD1-to-SOD2 Antioxidative Switch to Prevent Bone Cancer

2020 ◽  
Vol 10 (7) ◽  
pp. 2554
Author(s):  
Thomas S. Lisse
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Proliferating Cell Nuclear Antigen ◽  
Bone Cancer ◽  
Fold Increase ◽  
Nuclear Antigen ◽  
Pcr Analysis ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Complex Iv ◽  
Proliferating Cell

Superoxide, a form of reactive oxygen species (ROS), is catabolized by superoxide dismutase (SOD) and contributes to carcinogenesis via the oxidative damage it inflicts on cells. The aim of this research was to analyze the potential vitamin D-mediated regulation of the antioxidative “SOD1-to-SOD2 switch” within the human MG-63 osteosarcoma model. For this study, real-time PCR analysis was performed using MG-63 cells exposed to metabolically active 1,25(OH)2D3. First, a sustained statistically significant >2-fold suppression of proliferating cell nuclear antigen (PCNA) transcripts was observed after 10 nM but not at 100 nM of 1,25(OH)2D3 treatment, suggesting a cytostatic effect. In order to assess regulators of mitochondrial oxidative phosphorylation, gene expression of COX2 and COX4l1 of the mitochondrial complex IV and antioxidative enzymes (SOD1, SOD2 and Catalase (CAT)) were monitored. For COX2 and COX4l1, no changes in gene expression were observed. However, a concomitant decrease in CAT and SOD1 mRNA, and increase in SOD2 mRNA after 24 h of 10 nM 1,25(OH)2D3 treatment were observed. A ~8-fold increase in SOD2 mRNA was apparent after 48 ours. The significant increase in SOD2 activity in the presence of vitamin D indicates an antioxidant potential and sensitization of vitamin D during osteosarcoma transformation and mitochondrial detoxification over time.

Revealing the essentiality of multiple archaeal pcna genes using a mutant propagation assay based on an improved knockout method

Microbiology ◽  
2010 ◽  
Vol 156 (11) ◽  
pp. 3386-3397 ◽  
Author(s):  
Changyi Zhang ◽  
Li Guo ◽  
Ling Deng ◽  
Yuanxin Wu ◽  
Yunxiang Liang ◽  
...  
Keyword(s):  
Proliferating Cell Nuclear Antigen ◽  
Target Gene ◽  
Gene Deletion ◽  
Nuclear Antigen ◽  
Pcr Analysis ◽  
Sulfolobus Islandicus ◽  
Counter Selection ◽  
Micro Organisms ◽  
Proliferating Cell ◽  
Mutant Cells

Organisms belonging to the Crenarchaeota lineage contain three proliferating cell nuclear antigen (PCNA) subunits, while those in the Euryarchaeota have only one, as for Eukarya. To study the mechanism of archaeal sliding clamps, we sought to generate knockouts for each pcna gene in Sulfolobus islandicus, a hyperthermophilic crenarchaeon, but failed with two conventional knockout methods. Then, a new knockout scheme, known as marker insertion and target gene deletion (MID), was developed, with which transformants were obtained for each pMID-pcna plasmid. We found that mutant cells persisted in transformant cultures during incubation of pMID-pcna3 and pMID-araS-pcna1 transformants under counter selection. Studying the propagation of mutant cells by semiquantitative PCR analysis of the deleted target gene allele (Δpcna1 or Δpcna3) revealed that mutant cells could no longer be propagated, demonstrating that these pcna genes are absolutely required for host cell viability. Because the only prerequisite for this assay is the generation of a MID transformant, this approach can be applied generally to any micro-organisms proficient in homologous recombination.

scholarly journals The role of HER2/neu, BCL2, p53 genes and proliferating cell nuclear protein as molecular prognostic parameters in localized prostate carcinoma

2004 ◽  
Vol 122 (3) ◽  
pp. 124-127 ◽  
Author(s):  
Gilvan Neiva Fonseca ◽  
Miguel Srougi ◽  
Katia Ramos Moreira Leite ◽  
Luciano João Nesrallah ◽  
Valdemar Ortiz
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Proliferating Cell Nuclear Antigen ◽  
Proliferative Activity ◽  
Tumor Volume ◽  
Tumor Stage ◽  
Nuclear Antigen ◽  
Prognostic Parameters ◽  
P53 Expression ◽  
Proliferating Cell

CONTEXT: Prostate cancer is the most frequent solid genitourinary neoplasm in men. Involvement of several genes has been described in the promotion and progression of prostate carcinoma. OBJECTIVE: To study the expression of the oncogenes HER2/neu and BCL2, tumor suppressor gene p53 and the tumor proliferation rate in 150 radical prostatectomy specimens, in order to define their role as prognostic parameters in localized prostate cancer. TYPE OF STUDY: Prospective study. SETTING: Universidade Federal de São Paulo and Hospital Sírio Libanês, Sao Paulo PARTICIPANTS: One hundred and fifty men who were submitted to radical prostatectomy between August 1997 and August 1998, for localized prostate cancer. MAIN MEASUREMENTS: All specimens underwent evaluation in their entirety, to determine tumor volume percentage, tumor extent and Gleason score. Immunohistochemistry was performed to determine gene expression using anti- HER2/neu, BCL2 and p53 antibodies, and proliferating cell nuclear antigen. The chi-squared test was used for correlation between gene expression, proliferative activity and histological variables. RESULTS: Thirty percent of the cases were p53 positive. There was positive correlation between p53 expression and tumor stage. The p53 expression was 22.9% and 42.6% for pT2 and pT3 tumors, respectively (p = 0.01). Expression of HER2/neu, BCL2 and proliferating cell nuclear antigen was identified in 66%, 23% and 43% of patients, respectively. There was no correlation between these three parameters and tumor volume, Gleason score or tumor stage. CONCLUSION: One-third of prostate adenocarcinomas express p53 protein, and this characteristic is related to tumor stage. HER2/neu is frequently expressed in prostate carcinomas, with no correlation with histological parameters. BCL2 is rarely expressed, and together with proliferative activity has no relationship with prognostic pathological variables in these neoplasms.

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