Crabtree B, Gordon MJ, Christie SL

Crabtree B, Gordon MJ, Christie SL. and a good model to discuss new perspectives around the Warburg effect. Herein we provide new insight on how the somatic SC may be a source of new and exciting information concerning the Warburg effect and cell proliferation. strong class=”kwd-title” Keywords: Warburg effect, Sertoli cell, glycolysis, lactate, testis, spermatogenesis 1. INTRODUCTION Otto Warburg observed that glucose metabolism in cancer cells presents some specific characteristics very distinct from those of cells in normal tissues.1, 2 Warburg reported that cancer cells, unlike most normal cells, convert glucose to lactate even in the presence of sufficient and physiological oxygen levels to support mitochondrial oxidative phosphorylation. That was intriguing since most cells, in the presence of oxygen, metabolize glucose to carbon dioxide through the Krebs cycle by oxidation of pyruvate derived from glycolysis. This reaction produces NADH that is used as fuel to maximize ATP production by mitochondrial oxidative phosphorylation, with minimal lactate production. Thus, there are considerable differences in the metabolic behavior of Warburg cells versus normal cells. Normal CGP 37157 differentiated cells only produce high lactate levels under anaerobic conditions, while cancer cells produce high levels of lactate3 regardless of oxygen availability. Thus, in contrast to normal differentiated cells, which primarily rely on mitochondrial oxidative phosphorylation to generate energy, cancer cells obtain their energy by aerobic glycolysis, a process known as the Warburg effect. Warburg also postulated that glycolytic activity in cancer cells was comparable to that observed in early embryonic cells, illustrating that cancer cells may present a primitive metabolic pattern. 1 Proliferation is undoubtedly related to the unique metabolic CGP 37157 characteristics generally associated with cancer cells. Many unicellular organisms that present high proliferative activity use fermentation, the microbial equivalent of aerobic glycolysis, illustrating that aerobic glycolysis can produce sufficient energy to maintain cell proliferation. A cell that undergoes proliferation must replicate all of its cellular content to produce two viable daughter cells. For that purpose, several factors and special conditions are needed. Among those, large amounts of ATP and energy, nucleotides, amino acids, and lipids are required for biomass replication. Within the testis, biomass replication is usually CGP 37157 a crucial event, essential for the species maintenance and propagation. Thus, spermatogenesis, the process of sperm production and maturation, is usually under rigid control. In that process, the somatic Sertoli cell (SC) is usually a key element since SCs create the blood testis barrier (BTB), and they provide nutritional and structural support for the developing germ cells. SCs also protect spermatogenic cells from the host immune response Rabbit Polyclonal to AKAP13 and block the entry of leukocytes into the seminiferous epithelium (for review4). Thus, these CGP 37157 cells are responsible for the formation of an immune-privileged environment in the testis.5, 6 To accomplish all these functions, the SC presents some distinctive characteristics not always explored by researchers. One of the most important events during spermatogenesis is the metabolic cooperation between the SC and the developing CGP 37157 germ cells. The somatic SC presents a high glycolytic flux to ensure the production of high lactate levels and factors required for the developing germ cells. Indeed, the SC metabolic behavior aligns with Otto Warburg observations in cancer cells. However, besides the Warburg-like metabolism, the SC presents a very important characteristic related to their maturation. It is dependent on the species, but SCs can only proliferate during a specific time period and in all species (including humans) they cease to divide at adulthood..