Lactate and pyruvate promote cellular stress resistance and longevity through ROS signaling

Abstract

Enriched Pathways (ranked by p-value) a b PI3K/AKT pathway Diff. UP-regulated Diff. DOWN-regulated Pyruvate L-lactate 958 640 720 Pyruvate L-lactate 621 958 561

HCAR1/MCT1 Regulates Tumor Ferroptosis through the Lactate-Mediated AMPK-SCD1 Activity and Its Therapeutic Implications

“…A common feature among various cancer cells is that their metabolic pathways are rewired to aerobic glycolysis to facilitate cancer cell survival and growth (Kim and DeBerardinis, 2019), whereas lactate is the main metabolic product. Nevertheless, increasing evidence reveals that lactate is not a mere metabolic waste but a nutrient (Faubert et al, 2017;Hui et al, 2017) that has many regulatory roles in the tumor microenvironment, and it demonstrates particular relevance to oxidative stress resistance (Tasdogan et al, 2020;Tauffenberger et al, 2019) and lipid biosynthesis (Chen et al, 2016b). For instance, it has been confirmed that extracellular lactate is not only one of the major carbon sources for lipid biosynthesis but also could regulate the production of various lipid substances via AMP-activated protein kinase (AMPK) or signal transducer and activator of transcription 3 (STAT3) signaling (Pucino et al, 2019).…”

Nrf2 in TIME: The Emerging Role of Nuclear Factor Erythroid 2-Related Factor 2 in the Tumor Immune Microenvironment

“…Exposure to lactate increased the intracellular ROS and activated Nrf2 in neuroblastoma cells (SH-SY5Y) and Caenorhabditis elegans (Tauffenberger et al, 2019). Interestingly, the same study showed that lactate also caused activation of PI3K/AKT, but the possible involvement of AKT in the mechanism of Nrf2 activation by lactate has not been investigated.…”