S1P and plasmalogen derived fatty aldehydes in cellular signaling and functions

• Published in: Biochimica et biophysica acta. Molecular and cell biology of lipids 2020-07, Vol.1865 (7), p.158681-158681, Article 158681
• Main Authors: Ebenezer, David L., Fu, Panfeng, Ramchandran, Ramaswamy, Ha, Alison W., Putherickal, Vijay, Sudhadevi, Tara, Harijith, Anantha, Schumacher, Fabian, Kleuser, Burkhard, Natarajan, Viswanathan
• Format: Article
• Language: English
• Subjects: Hexadecenal; Long-chain fatty aldehydes; Lysoplasmalogenase; Plasmalogenase; S1P; S1P Lyase
• ISSN: 1388-1981; 1879-2618
• DOI: 10.1016/j.bbalip.2020.158681

Long-chain fatty aldehydes are present in low concentrations in mammalian cells and serve as intermediates in the interconversion between fatty acids and fatty alcohols. The long-chain fatty aldehydes are generated by enzymatic hydrolysis of 1-alkyl-, and 1-alkenyl-glycerophospholipids by alkylglycerol monooxygenase, plasmalogenase or lysoplasmalogenase while hydrolysis of sphingosine-1-phosphate (S1P) by S1P lyase generates trans ∆2-hexadecenal (∆2-HDE). Additionally, 2-chloro-, and 2-bromo- fatty aldehydes are produced from plasmalogens or lysoplasmalogens by hypochlorous, and hypobromous acid generated by activated neutrophils and eosinophils, respectively while 2-iodofatty aldehydes are produced by excess iodine in thyroid glands. The 2-halofatty aldehydes and ∆2-HDE activated JNK signaling, BAX, cytoskeletal reorganization and apoptosis in mammalian cells. Further, 2-chloro- and 2-bromo-fatty aldehydes formed GSH and protein adducts while ∆2-HDE formed adducts with GSH, deoxyguanosine in DNA and proteins such as HDAC1 in vitro. ∆2-HDE also modulated HDAC activity and stimulated H3 and H4 histone acetylation in vitro with lung epithelial cell nuclear preparations. The α-halo fatty aldehydes elicited endothelial dysfunction, cellular toxicity and tissue damage. Taken together, these investigations suggest a new role for long-chain fatty aldehydes as signaling lipids, ability to form adducts with GSH, proteins such as HDACs and regulate cellular functions. •Enzymatic or non-enzymatic reactions on membrane lipids generate highly reactive long-chain fatty aldehydes.•Long-chain fatty aldehydes, ∆2-hexadecenal and 2-chlorofatty aldehydes form adducts with proteins, glutathione and DNA.•∆2-Hexadecenal stimulates mitochondrial ROS via JNK, induces cytoskeletal reorganization and endothelial permeability.•Nuclear generation of ∆2-hexadecenal by sphingosine-1-phosphate lyase modulates HDAC1/2 activity.•∆2-Hexadecenal forms protein adducts with HDACs in vitro.