Neuroblastoma
Neuroblastoma, a term commonly used to refer to a spectrum of specific tumors that arise from primitive sympathetic ganglion cells, accounts for 97% of all neuroblastic tumors. They are clinically heterogeneous, varying in location, appearance and other characteristics. They also display a broad spectrum of clinical behavior, with some making for more difficult targets for treatment. Our work on TRPM2 aims to further our understanding and look for potential treatment targets by focusing on the role of TRPM2 in cell survival through modulation of oxidative stress.
TRPM2
Transient Receptor Potential Melastatin 2 (TRPM2) ion channel has an essential function in maintaining cell survival following oxidant injury. TRPM2 protects the viability of many cell types, including neuroblastoma, by maintaining mitochondrial function. When TRPM2 function is inhibited, mitochondria are dysfunctional, ROS production is increased, and cell viability is reduced, particularly after oxidative stress.
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TRPM2 in Neuroblastoma Proliferation and Survival
Transient Receptor Potential Melastatin 2 (TRPM2) ion channel plays an essential role in maintaining cell survival following oxidant injury, and thus protects the viability of many cell types, including neuroblastoma, by maintaining mitochondrial function. When TRPM2 function is inhibited, mitochondria are dysfunctional, ROS production is increased, and cell viability is reduced, particularly after oxidative stress. Our research is currently exploring the role of NF-E2-related factor (Nrf2) in TRPM2-mediated suppression of oxidant stress. We are exploring our findings that TRPM2 regulates levels of antioxidant cofactors glutathione (GSH), NADPH, and NADH through modulation of antioxidant enzymes which are transcriptionally regulated by Nrf2. Nrf2 was significantly decreased in TRPM2 depleted cells. Through multiple approaches we are pursing the pathways through which TRPM2 regulates cell viability via ROS levels including maintenance of antioxidant defenses regulated by Nrf2.