The Role of p38 MAPK in Triacylglycerol Accumulation during Apoptosis

Abstract

Lipids are emerging as key regulators of apoptosis. Specific lipid species are associated with apoptosis with important functional roles, but the understanding of the regulation of these lipid species is still limited. It has been previously shown by our laboratory that polyunsaturated triacylglycerols accumulate and get stored within lipid droplets during apoptosis via activated glycerolipid biosynthesis. In this work, the biochemical mechanisms that result in the activation of glycerolipid biosynthesis and, consequently, triacylglycerol and lipid droplet accumulation during apoptosis are investigated. The transcriptomes of control and apoptotic HCT‐116 cells are compared and gene enrichment analysis revealed the upregulation of p38 mitogen‐activated protein kinase (MAPK). It is shown that p38 MAPK regulates triacylglycerol biosynthesis through diacylglycerol acyltransferase1 during apoptosis. Perilipin 2 and cytosolic phospholipase A2delta are also shown to be involved in lipid droplet and polyunsaturated triacylglycerol accumulation in this process. Overall, the results provide new insights into the upregulation of glycerolipid synthesis during apoptosis.

Icariin alleviates high-fat diet-induced nonalcoholic fatty liver disease by up-regulating miR-206 to mediate the NF-κB and MAPK pathways

“…At present, it has been confirmed that NF-κB and MAPK, which widely exist in various cells of the body, are closely related to inflammation, liver fibrosis and liver failure in the development of NAFLD and NASH, and play an important role (24). Additionally, MAPK has been shown to regulate triacylglycerol biosynthesis through diacylglycerol acyltransferase during apoptosis and to be involved in the accumulation of cellular lipid droplets and polyunsaturated fatty acids (25). Furthermore, Kong et al discovered that ICA inhibited tumor necrosis factor-α (TNF-α)/interferon (IFN)-γ-induced inflammatory responses via inhibiting the substance P and p38-MAPK signaling pathways in human keratinocytes (26).…”

Icariin alleviates high‐fat diet‐induced nonalcoholic fatty liver disease via up‐regulating miR‐206 to mediate NF‐κB and MAPK pathways

“…Additionally, a study has demonstrated that MAPK regulated triacylglycerol biosynthesis through diacylglycerol acyltransferase during apoptosis; also, MAPK was involved in lipid droplet and polyunsaturated fatty acid accumulation in this process. [ 29 ] In addition, Kong et al discovered that ICA inhibited TNF‐α/IFN‐γ‐induced inflammatory responses via inhibiting substance P and p38‐MAPK signaling pathways in human keratinocytes. [ 30 ] In our research, ICA could regulate lipid droplet formation and inflammatory response in cells through regulating NF‐κB and MAPK signaling, consistent with the findings of previous studies.…”

Pyrimidine TAT TAC Kinases Promote B- Arrestins And Rac1 For Adopting Myocardial Constrictions And GPCRs Ratio By Ang2-AT2 Synthesis And Anti-Inflammatory Growth

“…That, beta-arrestin-1-dependent signaling pathway for p38 mitogen-activated protein kinase activation by beta2-adrenergic receptors [27]. That the rich Proline in activate hydrophobic acids synthesis (regulated by pyrimidine TAT TAC kinases) which activate IFN-beta and GC-beta ( mediated by MAPK function and by synthase for Acyl-COA-beta synthesis) that activate B-arrestins synthesis which adopt the glycoprotein ratio through binding to GPCR-B for stimulating ACE for Ang2-AT2 synthesis (from Ang1-AT1) which protect and adopt heart layers function , and also promote VEGF-A synthesis for adopting microvascular functions.…”