scholarly journals Effect of arsenic exposure on human telomerase reverse transcriptase (hTERT) gene expression: Risk of cardiovascular diseases

2019 ◽  
Vol 45 (1) ◽  
pp. 3-10
Author(s):  
Laila Khaleda ◽  
Mohammad Al Forkan ◽  
Fahmida Binta Wali ◽  
Md Jibran Alam ◽  
Amit Datta ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Mrna Expression ◽  
Cardiac Tissue ◽  
Open Heart Surgery ◽  
Arsenic Exposure ◽  
Mrna Levels ◽  
Strong Positive Correlation ◽  
Telomere Dysfunction ◽  
Htert Mrna ◽  
Htert Mrna Expression

Background: Exposure to inorganic arsenic (iAs) through drinking water is currently a serious threat to public health of millions of people worldwide including Bangladesh. Some recent studies have shown that telomere dysfunction is emerging as an important factor in the pathogenesis of different cardiovascular diseases. Arsenic plays significant role on telomere dysfunction by altering the expression of telomere-related genes. The study was aimed to investigate the effects of arsenic on hTERT mRNA levels and their combined role in increasing CVD susceptibility. Methods: In  this cross sectional study, total of 50 CVD patients who underwent open heart surgery were recruited for this study. Urine, nail and cardiac tissue samples were collected and analyzed for As. Blood samples were quantified for hTERT expression analysis using real-time polymerase chain reaction. Results: The hTERT mRNA expression was found approx. 10 fold higher in the As-exposed patients than the As-unexposed patients (p<0.01). A strong positive correlation (p<0.01, R>0.3) was found between the hTERT mRNA levels and As contents in the cardiac tissue, nail and urine samples of the study subjects. The significant increase (approx. 4 fold) in the hTERT mRNA expression was found in the patients with coronary artery disease (CAD) than the non-CAD patients. Conclusions: The results of the study suggest that arsenic exposure increases hTERT mRNA expression which may in turn modify As-induced cardiovascular outcomes. The findings of this study will help to look deep into the association of As exposure in cardiovascular disease pathogenesis to open a new window in the diagnosis and treatment procedure of CVD. Bangladesh Med Res Counc Bull 2019; 45: 03-10

scholarly journals EGFR and hTERT Expression as a Diagnostic Approach for Non-small Cell Lung Cancer in High Risk Groups

2010 ◽  
Vol 2 ◽  
pp. BIC.S3383 ◽  
Author(s):  
Radostina Cherneva ◽  
Ognian Georgiev ◽  
Ivanka Dimova ◽  
Blaga Rukova ◽  
Danail Petrov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
High Risk ◽  
Small Cell Lung Cancer ◽  
Mrna Expression ◽  
Small Cell ◽  
Htert Mrna ◽  
Small Cell Lung ◽  
The Mean ◽  
Htert Mrna Expression

Objective The early detection of NSCLC is of importance because it provides chances for better outcomes. The aim of the study was to explore the clinical utility of EGFR and hTERT mRNA expression as markers for diagnosis of NSCLC. Methods EGFR and hTERT mRNA were quantified by quantative reverse transcription real time polymerase chain reaction in plasma of 45 non-small cell lung cancer (NSCLC) and 40 chronic obstructive pulmonary disease (COPD) patients, selected by certain spirometric characteristics that made them at high risk of developing lung cancer in future. Results The gene expression level of each gene was calculated and given as a relative quantity–-RQ. EGFR gene expression was found in all lung cancer patients. The mean level of expression was RQ = 29.39. hTERT mRNA could be detected in 88% of patients. The mean expression ratio in them was RQ = 17.31. Only 50% of the high risk patients turned to be positive for EGFR. The level of their expression was RQ = 2.09. The plasma levels of hTERT could be detected in 17 (42.5%) patients of the high risk COPD group. Their mean level of expression was RQ = 1.02. A statistically significant difference in EGFR and hTERT mRNA expression could be observed between the two groups of patients–-p = 0.0001. Conclusion EGFR and hTERT mRNA are potential markers for lung cancer diagnosis, whose clinical importance should be replicated in a larger cohort of patients.

scholarly journals miR-19b regulates hTERT mRNA expression through targeting PITX1 mRNA in melanoma cells

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Takahito Ohira ◽  
Sunamura Naohiro ◽  
Yuji Nakayama ◽  
Mitsuhiko Osaki ◽  
Futoshi Okada ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Melanoma Cells ◽  
Htert Mrna ◽  
Htert Mrna Expression

The Regulation of Telomere Binding Proteins on Telomerase during Differentiation of ATRA Responsive and Resistant NB4 Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3390-3390
Author(s):  
He Huang ◽  
Jie Sun ◽  
Yuan Yuan Zhu ◽  
Jian Ping Lan ◽  
Xiao Yu Lai
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Peak Level ◽  
Telomerase Activity ◽  
Expression Level ◽  
Htert Mrna ◽  
Down Regulation ◽  
Nb4 Cells ◽  
Significant Change ◽  
Htert Mrna Expression

Abstract It has been reported that the down-regulation of telomerase activity associated with maturation of APL cells is not mechanistically linked to cell maturation, and requires only a RAR, but not a RXR-dependent pathway. However, it is not clear whether and how telomeric proteins respond to the retinoid treatment. Using maturation-sensitive and resistant APL cell lines NB4, NB4-R1 and NB4-R2 cells, we analyzed a panel of telomeric proteins using western blotting analyses in addition to temporal profile of corresponding mRNA during the course of retinoid-induced differentiation. Our analyses show hTERTmRNA expression decreased rapidly during differentiation of NB4 and NB4-R1 cells, telomerase activity also declined. But in NB4-R2 cells, hTERT mRNA was initially decreased to 38.2% on day1 (P<0.05) and then increased to 80.0% on day 3 (P<0.05). Telomerase activity remained unchanged overtime (P>0.05), which may be caused by the increasing of hTERT mRNA expression during its later period of differentiation. TRF1 mRNA and protein expression have no significant change during differentiation in NB4 and NB4-R1 cells but has a small increase in NB4-R2 cells. The TRF1 mRNA expression level has no significant change during differentiation of NB4 and NB4-R1 cell line cells. However, it was increased to 235% on day 2 (P<0.05) and remains at this level until day 3 during the differentiation of NB4-R2 cells. TRF1 protein expression level also remains stable during differentiation of NB4 and NB4-R1 cells, but has a little increase in NB4-R2 cells. This indicates TRF1 has different regulation in RARα dependent or RXRα dependent pathways. Pinx1 mRNA expression decreased during the differentiation of NB4 and NB4-R1. But during the differentiation of NB4-R2, Pinx1mRNA expressions level was initially decreased to 34.3% (P<0.05) on day 1 then increased to 64.5% (P<0.05 compared to day1) on day2. The change of Pinx1 mRNA expression and hTERT mRNA expression in NB4(r=0.902, P=0.036), NB4-R1(r=1.00, P<0.001), and NB4-R2(r=0.880, P=0.049) cells are positive correlated. Pinx1 is the only telomere binding protein that can bind to hTERT directly, it might be responsible for the different regulation of telomerase activity through RARα dependent or RXRα dependent pathways. During NB4 cell differentiation, TANK1 mRNA expression decreased gradually to 31.6% (P<0.05) on day1, and remained this level until day3. In NB4-R1 cells, TANK1 mRNA expression increased initially to 197% at 12h(P<0.05), and then decreased gradually to 111% (P<0.05) on day 3. During the differentiation of NB4-R2 cells, TANK1 mRNA expression was initially increased to 204% at 12h(P<0.01), and then decreased gradually to 96.9% on day3 (P<0.01). Its protein expression initially increased and reached a peak level at day 1 and then decreased in the later period of differentiation of all three NB4 cells. Both TANK1 mRNA expression and its protein expression were down-regulated at the later period of differentiation in all three NB4 cells. It seems that TANK1 may act as a positive regulator on telomerase activity during differentiation. TANK2 mRNA expression remained no change during differentiation of three NB4 cells. As results show, Pinx1 and TANK1 may interfere in the regulation of telomerase. The decrease of TANK1 may be the cause of the down-regulation of telomerase activity. Further studies will focus on the mechanism of their regulation on telomerase.

The evaluation of hTERT mRNA expression in acute leukemia children and 2 years follow-up of 40 cases

2008 ◽  
Vol 87 (3) ◽  
pp. 276-283 ◽  
Author(s):  
Ozgur Cogulu ◽  
Buket Kosova ◽  
Cumhur Gunduz ◽  
Emin Karaca ◽  
Serap Aksoylar ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Mrna Expression ◽  
Htert Mrna ◽  
Htert Mrna Expression

Effect of indomethacin on the growth response, c-myc mRNA expression, and hTERT mRNA expression in colon cancer cells

2001 ◽  
Vol 120 (5) ◽  
pp. A165-A165
Author(s):  
T SHIMADA ◽  
T KUNIYOSHI ◽  
K KOJIMA ◽  
Y MITOBE ◽  
T MITSUHASHI ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Growth Response ◽  
Htert Mrna ◽  
Colon Cancer Cells ◽  
Htert Mrna Expression

Study on Expression of Telomerase Inhibitor Pinx1 in Leukemia Cells and Its Correlation with Telomerase Activity.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4375-4375
Author(s):  
Jie Sun ◽  
He Huang ◽  
Yuanyuan Zhu ◽  
Jianping Lan ◽  
Xiaoyu Lai
Keyword(s):  
Acute Leukemia ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Telomerase Activity ◽  
Leukemia Cells ◽  
Htert Mrna ◽  
Normal Bone ◽  
Telomerase Inhibitor ◽  
Telomere Binding Protein ◽  
Htert Mrna Expression

Abstract Telomere shortens and telomerase activation was found both in malignant hematological cell line cells and leukemia samples. However, the mechanism of telomerase activation is unclear. The regulation of telomerase activity could be explained by many aspects, telomere binding protein is one of the new one. Pinx1 is an inhibitor of telomerase activity. Overexpression of Pinx1 inhibits telomerase activity, shortens telomeres, and induces crisis, whereas depletion of endogenous Pinx1 increases telomerase activity and elongates telomeres. However, how does Pinx1 act on telomerase in malignant tumor cells is not clear. In this study, we detected the expression of telomerase inhibitor Pinx1 in acute leukemia cells and during the differentiation of acute promyelocytic leukemia cells to realize its effect on telomerase activity and the probable mechanism inside. 30 acute leukemia cases were all enrolled at their first diagnose, 17 samples were of acute non-lymphocytic leukemia (ANLL) while 13 of acute lymphoblastic leukemia (ALL). Realtime quantitative PCR with fluorescence probe hybridization was used to measure expression of Pinx1 and hTERT mRNA in acute leukemia cells and during differentiation of NB4 cells induced by ATRA. NB4 cells at the initial concentration of 1×105/ml were treated with 1uM ATRA. Cells were collected at 5 time points as 0h, 12h, 24h, 48h and 72h. Pinx1 mRNA expression in acute leukemia samples(0.00312, 5.42×10−4~0.024)is significantly higher than that in normal bone marrow mononuclear cells(7.89×10−4, 0~0.00863)(P<0.01=. Both its expression in ANLL cells(0.00296, 0.00103~0.0182)( P<0.05=and ALL cells(0.00327, 5.42×10−4~0.024) (P<0.05= were higher than that in normal bone marrow mononuclear cells. The expression of Pinx1 mRNA had significant positive correlation with hTERT mRNA expression (r=0.296, P<0.05=. Pinx1 mRNA expression decreased during NB4 cell differentiation, its expression was positive correlated with hTERT mRNA expression (r=0.900, P<0.05=. Why telomerase was activated in malignant tumor cells is unclear yet. It was considered to be activated after telomere length shortened to an extent. So telomere binding proteins may play an important role in telomerase activation. Pinx1 was regarded as a negative regulator of telomerase. It was reported that Pinx1 expression was significantly reduced in many human tumor samples including liver, prostate, colon and lung carcinoma. But some studies showed Pinx1 expression has no significant change in human gastrointestinal tract carcinoma and in human hepatocellular carcinoma. We found Pinx1 expression increased in acute leukemia cells and decreased during NB4 cell differentiation, positive correlated with hTERT mRNA expression As Pinx1 is the only telomere binding protein that can bind to hTERT directly, we hypothesized that the variation of Pinx1 mRNA expression during differentiation acted as a negative feedback to hTERT for stabilization of telomerase activity. When hTERT levels increased, more Pinx1 would be bound with hTERT resulting in reduced free Pinx1 protein in cells. This in turn caused compensate increase in Pinx1 transcription. When hTERT decreased, amount of free Pinx1 protein would increase and result in decrease in Pinx1 mRNA expression. So Pinx1’s variation may be a subsequent reaction induced by that of hTERT during differentiation, though the exact mechanism needs further studies.

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