Abstract
The glycolytic modulator TP53-Inducible Glycolysis and Apoptosis Regulator (TIGAR) is overexpressed in several types of cancer and has a role in metabolic rewiring during tumor development. However, little is known about the role of this enzyme in proliferative tissues under physiological conditions. In the current work, we analysed the role of TIGAR in primary human lymphocytes stimulated with the mitotic agent Concanavalin A (ConA). We found that TIGAR expression was induced in stimulated lymphocytes through the PI3K/AKT pathway, since Akti-1/2 and LY294002 inhibitors prevented the upregulation of TIGAR in response to ConA. In addition, suppression of TIGAR expression by siRNA decreased the levels of the proliferative marker PCNA and increased cellular ROS levels. In this model, TIGAR was found to support the activity of glucose 6-phosphate dehydrogenase (G6PDH), the first enzyme of the pentose phosphate pathway (PPP), since the inhibition of TIGAR reduced G6PDH activity and increased autophagy. In conclusion, we demonstrate here that TIGAR is upregulated in stimulated human lymphocytes through the PI3K/AKT signaling pathway, which contributes to the redirection of the carbon flux to the PPP.
Highlights
T lymphocytes, known as T cells, are key players in the adaptative immune system.They participate in cellular immunity by targeting infected or cancerous cells, and in humoral immunity by recruiting and activating other immune cells such as macrophages orB lymphocytes [1,2]
We showed that PFKFB3 mRNA and protein levels were increased upon treatment of human T-lymphocytes with mitogenic stimuli that induced activation and proliferation of these cells, concomitantly with GLUT-1 and HK-II expression
TP53-Inducible Glycolysis and Apoptosis Regulator (TIGAR) Is Induced in Concanavalin A (ConA)-Activated Human Lymphocytes
Summary
T lymphocytes, known as T cells, are key players in the adaptative immune system.They participate in cellular immunity by targeting infected or cancerous cells, and in humoral immunity by recruiting and activating other immune cells such as macrophages orB lymphocytes [1,2]. T lymphocytes, known as T cells, are key players in the adaptative immune system. They participate in cellular immunity by targeting infected or cancerous cells, and in humoral immunity by recruiting and activating other immune cells such as macrophages or. T lymphocytes are produced in the bone marrow and continue their development in the thymus, where they mature into naïve T cells. Once they enter circulation, naïve T cells are maintained in a resting or quiescent state by T cell receptor (TCR). Upon encountering an external antigen, which generally occurs in lymphoid tissues, naïve T cells differentiate into effector
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
