scholarly journals Effects of the human papilloma virus HPV-16 E7 oncoprotein on glycolysis and glutaminolysis: role of pyruvate kinase type M2 and the glycolytic-enzyme complex

2001 ◽  
Vol 356 (1) ◽  
pp. 247 ◽  
Author(s):  
Sybille MAZUREK ◽  
Werner ZWERSCHKE ◽  
Pidder JANSEN-DÜRR ◽  
Erich EIGENBRODT
2001 ◽  
Vol 356 (1) ◽  
pp. 247-256 ◽  
Author(s):  
Sybille MAZUREK ◽  
Werner ZWERSCHKE ◽  
Pidder JANSEN-DÜRR ◽  
Erich EIGENBRODT

Proliferating and tumour cells express the glycolytic isoenzyme, pyruvate kinase type M2 (M2-PK), which occurs in a highly active tetrameric form and in a dimeric form with low affinity for phosphoenolpyruvate. The switch between the two forms regulates glycolytic phosphometabolite pools and the interaction between glycolysis and glutaminolysis. In the present study, we show the effects of oncoprotein E7 of the human papilloma virus (HPV)-16 (E7)-transformation on two NIH 3T3 cell strains with different metabolic characteristics. E7-transformation of the high glycolytic NIH 3T3 cell strain led to a shift of M2-PK to the dimeric form and, in consequence, to a decrease in the cellular pyruvate kinase mass-action ratio, the glycolytic flux rate and the (ATP+GTP)/(UTP+CTP) ratio, as well as to an increase in fructose 1,6-bisphosphate (FBP) levels, glutamine consumption and cell proliferation. The low glycolytic NIH 3T3 cell strain is characterized by high pyruvate and glutamine consumption rates and by an intrinsically large amount of the dimeric form of M2-PK, which is correlated with high FBP levels, a low (ATP+GTP)/(CTP+UTP) ratio and a high proliferation rate. E7-transformation of this cell strain led to an alteration in the glycolytic-enzyme complex that correlates with an increase in pyruvate and glutamine consumption and a slight increase in the flow of glucose to lactate. The association of phosphoglyceromutase within the glycolytic-enzyme complex led to an increase of glucose and serine consumption and a disruption of the linkage between glucose consumption and glutaminolysis. In both NIH 3T3 cell lines, transformation increased glutaminolysis and the positive correlation between alanine and lactate production.


Author(s):  
Asma Shabbir

Background: Oral cancer is a major problem globally. The strong causal association with tobacco, prevalent in Pakistan makes it imperative to know the role of molecular events in oral oncogenesis. We aim to evaluate high risk HPV 16/18 and p16 in oral premalignant lesions (OPL) and oral squamous cell carcinoma (OSCC). We further analyze the association between high risk human papilloma virus (HR-HPV16/18) and p16 in OPL and OSCC. Methods: A total of 100 OSCC and 50 OPL cases were included. Demographic data along with habitual exposure to smoked and chewable tobacco, betel and gutka etc., was noted. We evaluated p16 in OPL and OSCC by immunohistochemistry, HPV was detected by polymerase chain reaction. Data was entered and analyzed using SPSS 21. Chi square and Fisher exact were applied to determine the association of HPV and p16 with different variables. Results: Out of 50 OPL, 14% were positive and 86% were negative for p16 whereas out of 100 OSCC, 18% were positive and 82% were negative. Out of 50 OPL, HPV was detected in 6% whereas out of 100 OSCC, 15% were positive. Highly significant co expression of HPV with p16 was observed in all 15 (100%) HPV positive OSCC cases (p = 0.001). However, 3 out of 18 cases, which showed p16 expression, did not show HPV infection. Conclusion: Role of p16 as a surrogate marker for HPV in OSCC can be supported in the present study. Moreover a Chemical carcinogen like tobacco is considered as major associative risk factor with p16 and HPV in concert.


2018 ◽  
Vol 19 (9) ◽  
pp. 798-805 ◽  
Author(s):  
Mohd Saeed ◽  
Fawaz D. Alshammari ◽  
Md. Jahoor Alam ◽  
Khan Mohd Sarim ◽  
Khurshid Ahmad ◽  
...  

Author(s):  
Naomi Morka ◽  
Joseph M. Norris ◽  
Mark Emberton ◽  
Daniel Kelly

AbstractProstate cancer affects a significant proportion of men worldwide. Evidence from genetic and clinical studies suggests that there may be a causal association between prostate cancer and the human papilloma virus (HPV). As HPV is a vaccine-preventable pathogen, the possibility of a role in prostate cancer causation may reinforce the importance of effective HPV vaccination campaigns. This is of particular relevance in light of the COVID-19 pandemic, which may have considerable effects on HPV vaccine uptake and distribution.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Martin Fischer ◽  
Sigrid Uxa ◽  
Clara Stanko ◽  
Thomas M. Magin ◽  
Kurt Engeland

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Luca Fiorillo ◽  
Gabriele Cervino ◽  
Giovanni Surace ◽  
Rosa De Stefano ◽  
Luigi Laino ◽  
...  

The human papilloma virus (HPV) is responsible for different pathological manifestations in humans. This agent gives rise to lesions of different types and in different areas of the organism, including the oral cavity. The aim of this study is to show which are the main diseases for which HPV is responsible and to bring to light some of the interceptive and therapeutic strategies. The analysis was conducted by consulting the major scientific databases with the aim of obtaining information on the characteristics of oral HPV and its management; furthermore, the literature was supported by some clinical cases proposed by the authors. The role of dentistry is essential in the early diagnosis of this type of pathologies and above all in knowing how to direct patients towards a path that can lead to patient management, especially in the event that these lesions have a malignant potential. Enhancing the knowledge and role of dentistry can lead to early diagnosis of this type of injury, intercepting a pathology that could have multiorgan implications.


2018 ◽  
Vol 18 (1) ◽  
pp. 215
Author(s):  
Nia Nurzia

Abnormal cervical is still  in high levels of  which marked by the outbreak of the Human Papilloma Virus, It is not offset by the use of vaccination (HPV) Human Papilloma Virus which as the primary prevention of the spread of Human Papilloma Virus . recorded in Dara Jingga clinic in  2015, there were 226 people in the state of the cervix abnormal while those who making vaccination extremely low at only 40 people. Likewise, in 2016 there were 301 people in a state of abnormal cervical and vaccinated only 16 people . Based on it, this research is the research which aimed to determine the relationship between knowledge, economic status, family role and the role of health personnel  against the Human Papilloma Virus vaccination in Dara Jingga Clinic  Jambi City. This research is descriptive analytic with cross sectional design, the data collected through questionnaires, with a population was 321 people. using  acidental sampling technique with  sample was 32 people, research has been conducted on 22 to 24 August 2016 using univariate  and bivariate analysis assisted by a computer program. The results of the univariate analysis of vaccination picture were 10 respondents (31.3%) take advantage of HPV vaccination and 22 respondents (68,8%) did not take advantage of the HPV vaccination, an overview of knowledge were five respondents (15,6%) have sufficient knowledge, 15 respondents (46,9%) had a good knowledge,12 respondents (37,5%) had poor knowledge, an overview of economic status,  13 respondents (40,6%) had high economic status and  19 respondents (59,4% ) have lower economic status, description of the role of health workers13 respondents (40,6%) have a good role of health personnel and  19 respondents (59,4%) has the role of health personnel is not good. Overview of the role of the family, 11 respondents (34,4%) has the role of a good family and  21 respondents (65,6%) had a family roles goodles. the result of these studies show a relationship between the mother's knowledge by vaccination with HPV (Human Papilloma Virus ) with a p value of 0,035, the relationship between economic status with vaccination HPV (Human Papilloma Virus with p value 0,002, their relationship with the role of HPV vaccination of health workers with p value 0,002, their relationship with the family role of HPV vaccination with a p value of 0,004.Keywords: Knowledge, Economic Status, Role of health personnel, Role of Family,HPV Vaccination (Human Papilloma Virus)


2018 ◽  
Author(s):  
Jamie A. Macpherson ◽  
Alina Theisen ◽  
Laura Masino ◽  
Louise Fets ◽  
Paul C. Driscoll ◽  
...  

ABSTRACTAllosteric regulation is central to the role of the glycolytic enzyme pyruvate kinase M2 (PKM2) in cellular metabolism. Multiple activating and inhibitory allosteric ligands regulate PKM2 activity by controlling the equilibrium between high activity tetramers and low activity dimers and monomers. However, it remains elusive how allosteric inputs upon simultaneous binding of different ligands are integrated to regulate PKM2 activity. Here, we show that, in the presence of the allosteric inhibitor L-phenylalanine (Phe), the activator fructose 1,6-bisphosphate (FBP) can induce PKM2 tetramerisation, but fails to maximally increase enzymatic activity. Guided by a new computational framework we developed to identify residues that mediate FBP-induced allostery, we generated two PKM2 mutants, A327S and C358A, in which activation by FBP remains intact but cannot be attenuated by Phe. Our findings demonstrate a role for residues involved in FBP-induced allostery in enabling the integration of allosteric input from Phe and reveal a mechanism that underlies the co-ordinate regulation of PKM2 activity by multiple allosteric ligands.


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