4/10/2023 0 Comments 118 overloop 12550In addition, C1P plays an important role in phagocytosis, and we have recently demonstrated that is a key factor in the regulation of macrophage chemotaxis. There is increasing evidence suggesting that C1P can regulate cell proliferation and apoptosis, and Chalfant and co-workers have elegantly demonstrated that C1P is a potent pro-inflammatory agent (Reviewed in ). Formation of ceramide is also relevant because it is the precursor of important bioactive sphingolipids that can also regulate cellular functions, as discussed below.Ī major metabolite of ceramide is ceramide-1-phosphate (C1P), which is generated through direct phosphorylation of ceramide by ceramide kinase (CerK) (Fig. However, in many studies short-chain analogs (N-acetylsphingosine, or C 2-ceramide, N-hexanoylsphingosine, or C6-ceramide, and N-octanoylsphingosine, or C8-ceramide) have been used in experiments because these are more water soluble than long-chain ceramides. Cell ceramides typically have long N-acyl chains ranging from 16 to 26 carbons in length. Also, ceramides play important roles in the regulation of autophagy, cell differentiation, survival, and inflammatory responses, and have been associated with insulin resistance through activation of protein phosphatase 2A and the subsequent dephosphorylation and inactivation of Akt (also known as protein kinase B (PKB)). Specifically, ceramides induce cell cycle arrest and promote apoptosis, a form of programmed cell death. In particular, ceramide is the central core in sphingolipid metabolism, but has also been involved in the regulation of signal transduction processes. Sphingolipids play essential roles in normal cell and tissue homeostasis as well as in the establishment and progression of numerous diseases. Hence, it can be concluded that C1P has dual actions in cells, as it can act as an intracellular second messenger to promote cell survival, or as an extracellular receptor agonist to stimulate cell migration. However, the recent observation that C1P stimulates macrophage chemotaxis implicates specific plasma membrane receptors that are coupled to Gi proteins. All of the former actions are thought to be mediated by intracellularly generated C1P. In addition, C1P is an important mediator of inflammatory responses, an action that takes place through stimulation of cytosolic phospholipase A2, and the subsequent release of arachidonic acid and prostaglandin formation. C1P is mitogenic and has prosurvival properties. ![]() Phosphorylation of ceramide produces ceramide 1-phosphate (C1P), which has opposite effects to ceramide. Two major actions of ceramides are the promotion of cell cycle arrest and the induction of apoptosis. In particular, ceramide plays crucial roles in cell signaling processes. ![]() Sphingolipids are essential components of cell membranes, and many of them regulate vital cell functions.
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