Browsing by Author "Conchinha, Nadine Vasconcelos"
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- Role of fatty acid oxidation in quiescent endothelial cellsPublication . Conchinha, Nadine VasconcelosEndothelial cells (ECs) are located in the innermost layer of blood vessels and are in direct contact with the blood stream. ECs in established, healthy blood vessels are quiescent and most of them can stay in their quiescent state for many years but when stimulated under physiological or pathological conditions, they become proliferative and allow vessel growth (process called angiogenesis). Due to their key localization, ECs are involved in many different functions like fluid filtration, blood vessel tone, homeostasis and oxygen and nutrients supply. Thus, it is not surprising that when ECs become dysfunctional, they contribute to a large range of diseases like hypertension, atherosclerosis, thrombosis, leakage, stroke, tissue ischemia, etc. The host lab already characterized some metabolic features of proliferating ECs that are affecting sprouting and migration of ECs cells. These studies showed that EC metabolism could be a promising target for anti-angiogenesis therapies. However, in spite of recent advances, the metabolism of the quiescent endothelium remains incompletely understood. In this project we sought to study the metabolic changes facilitating the switch from proliferating to quiescent ECs. Our first results showed that during this switch glucose oxidation and glycolytic flux are reduced, whereas fatty acid ß-oxidation (FAO) is increased. As quiescent ECs are exposed to an oxygen-rich microenvironment, we hypothesize that the FAO derived acetyl-CoA fuels the TCA cycle to produce NADPH to preserve the redox homeostasis of the cell. Mechanistically, activation of Notch signaling pathway regulate the induction of the metabolic changes in quiescent ECs.
- The tumorigenic roles of the cellular REDOX regulatory systemsPublication . Castaldo, Stephanie Anais; Freitas, Joana Raquel; Conchinha, Nadine Vasconcelos; Madureira, Patrícia A.The cellular REDOX regulatory systems play a central role in maintaining REDOX homeostasis that is crucial for cell integrity, survival, and proliferation. To date, a substantial amount of data has demonstrated that cancer cells typically undergo increasing oxidative stress as the tumor develops, upregulating these important antioxidant systems in order to survive, proliferate, and metastasize under these extreme oxidative stress conditions. Since a large number of chemotherapeutic agents currently used in the clinic rely on the induction of ROS overload or change of ROS quality to kill the tumor, the cancer cell REDOX adaptation represents a significant obstacle to conventional chemotherapy. In this review we will first examine the different factors that contribute to the enhanced oxidative stress generally observed within the tumor microenvironment. We will then make a comprehensive assessment of the current literature regarding the main antioxidant proteins and systems that have been shown to be positively associated with tumor progression and chemoresistance. Finally we will make an analysis of commonly used chemotherapeutic drugs that induce ROS. The current knowledge of cancer cell REDOX adaptation raises the issue of developing novel and more effective therapies for these tumors that are usually resistant to conventional ROS inducing chemotherapy.
- The tumorigenic roles of the cellular REDOX regulatory systemsPublication . Castaldo, Stéphanie Anais; Freitas, Joana Raquel; Conchinha, Nadine Vasconcelos; Madureira, Patrícia A.The cellular REDOX regulatory systems play a central role in maintaining REDOX homeostasis that is crucial for cell integrity, survival, and proliferation. To date, a substantial amount of data has demonstrated that cancer cells typically undergo increasing oxidative stress as the tumor develops, upregulating these important antioxidant systems in order to survive, proliferate, and metastasize under these extreme oxidative stress conditions. Since a large number of chemotherapeutic agents currently used in the clinic rely on the induction of ROS overload or change of ROS quality to kill the tumor, the cancer cell REDOX adaptation represents a significant obstacle to conventional chemotherapy. In this review we will first examine the different factors that contribute to the enhanced oxidative stress generally observed within the tumor microenvironment. We will then make a comprehensive assessment of the current literature regarding the main antioxidant proteins and systems that have been shown to be positively associated with tumor progression and chemoresistance. Finally we will make an analysis of commonly used chemotherapeutic drugs that induce ROS. The current knowledge of cancer cell REDOX adaptation raises the issue of developing novel and more effective therapies for these tumors that are usually resistant to conventional ROS inducing chemotherapy.