Sphingolipid synthesis and role in uterine epithelia proliferation

Abstract

Sphingolipids are involved in the regulation of cell proliferation. It has been reported that diacylglycerol and sphingosine-1-phosphate generation, during the synthesis of phospho-sphingolipids, is necessary for both, G1-S transition of cell cycle during the sustained activation of protein kinase C in various cell models (MDCK, and) and AKT pathway activation. During the estrous cycle of the rat, AKT signaling is the main pathway involved in the regulation of uterine cell proliferation. The aim of the present study was to investigate the role of sphingolipid synthesis during proliferation of uterine cells in the estrous cycle of the rat. On metestrus day, when both luminal and glandular uterine epithelia present the maximal BrdU-labeled cells (S phase cells), there was an increase in the relative abundance of total sphingomyelins, as compared to estrus day. Myriocin, a sphingolipid synthesis inhibitor administered on estrus day, before the new cell cycle of epithelial cells is initiated, decreased the abundance of sphingomyelin, accompanied by proliferation arrest in uterine epithelial cells on metestrus day. In order to study the sphingolipid signaling pathway affected by myriocin, we evaluated the activation of the PKC-AKT-GSK3b-Cyclin D3 pathway. We observed that total and phosphorylated protein kinase C diminished in uterine epithelial cells of myriocin treated animals. Interestingly, cyclin D3 nuclear localization was blocked by myriocin, concomitantly with a decrease in nuclear pRb expression. In conclusion, we demonstrate that sphingolipid synthesis and signaling are involved in uterine epithelial cell proliferation during the estrous cycle of the rat.

Dietary Supplementation of Lauric Acid Alleviates the Irregular Estrous Cycle and the Impaired Metabolism and Thermogenesis in Female Mice Fed with High-Fat Diet (HFD)

“…The conflicting data might be due to the species or experimental processing time. Similar to our result, many research results found that the LPC decreased in HFD mice , and obese humans. , In addition, it has been demonstrated that SM synthesis increased during proliferation of uterine cells in the estrous cycle of the rat . Furthermore, endometrial PE increased late in the oestrous cycle in the ewe, and the concentrations of the SM, phospholipids, and LPC increased at different stages of the estrous cycle of bovine .…”

Simulated microgravity significantly altered metabolism in epidermal stem cells

“…Several SPL metabolites, especially ceramide (Cer) and sphingomyelin (SM), act as key bioactive molecules to control critical cellular functions, such as cell cycle, aging, apoptosis, cell migration, and inflammation (Hannun and Obeid 2008). Cerbón et al (2018) reported that, myriocin, an inhibitor of sphingolipid synthesis, is used during estrus, before the start of the new cell cycle in epithelial cells. The results showed that the abundance of sphingomyelin was reduced, accompanied by the stagnation of the proliferation of uterine epithelial cells on metestrus day.…”

Overexpression of LASS2 inhibits proliferation and causes G0/G1 cell cycle arrest in papillary thyroid cancer

“…However, p21 was also known to be regulated by p53-independent signaling pathway [ 35 , 36 ]. During the synthesis of phospho-sphingolipids, the generation of diacylglycerol and sphingosine-1-phosphate is necessary for the G1-S transition of cell cycle [ 37 ]. Sphingolipid pathway-mediated the activation of the NF-κB [ 38 ].…”