碱性鞘磷脂酶与脂类代谢相关疾病的研究进展
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摘要
碱性鞘磷脂酶(Alk-SMase)存在于肠道和人的胆汁中,是消化道中水解鞘磷脂的关键酶。鞘磷脂的消化水解作用减弱,代谢活性产物减少,将导致细胞增生、凋亡、炎症等失去调控,最终导致癌症的发生。脂类代谢是人类体内重要的代谢过程,Alk-SMase及其代谢产物也能影响肠道中磷脂、胆固醇和三酰甘油等脂类的代谢,最终导致肝胆疾病、肠道炎症以及结肠肿瘤的发生。本文将重点讨论Alk-SMase与脂类代谢的关系,对近年来AlkSMase与脂类代谢相关疾病的研究进展作一简要综述。
Alkaline sphingomyelinase(Alk-SMase) is the key enzyme for the hydrolysis of sphingomyelin in the digestive tract, which exists in the intestine and human bile. Decreased sphingomyelin hydrolysis and metabolic active products will cause cell proliferation, apoptosis, inflammation and ultimately leading to cancer. Lipid metabolism is an important metabolic process in humans. Alk-SMase and its metabolites can affect the metabolism of phospholipids,cholesterol and triglycerides in the intestine, leading to hepatobiliary diseases, intestinal inflammation and colon tumors. This article will focus on the relationship between Alk-SMase and lipid metabolism, and make a brief review of the research progress of Alk-SMase and lipid metabolism related diseases.
Alkaline sphingomyelinase(Alk-SMase) is the key enzyme for the hydrolysis of sphingomyelin in the digestive tract, which exists in the intestine and human bile. Decreased sphingomyelin hydrolysis and metabolic active products will cause cell proliferation, apoptosis, inflammation and ultimately leading to cancer. Lipid metabolism is an important metabolic process in humans. Alk-SMase and its metabolites can affect the metabolism of phospholipids,cholesterol and triglycerides in the intestine, leading to hepatobiliary diseases, intestinal inflammation and colon tumors. This article will focus on the relationship between Alk-SMase and lipid metabolism, and make a brief review of the research progress of Alk-SMase and lipid metabolism related diseases.
引文
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[14]Zhang P,Chen Y,Cheng Y,et al.Alkaline sphingomyelinase(NPP7)promotes cholesterol absorption by affecting sphingomyelin levels in the gut:A study with NPP7knockout mice[J].Am J Physiol Gastrointest Liver Physiol,2014,306(10):G903-908.
[15]Venuti E,Shishmarev D,Kuchel PW,et al.Bile salt stimulated lipase:Inhibition by phospholipids and relief by phospholipase A2[J].J Cyst Fibros,2017,16(6):763-770.
[16]Rezhdo O,Di Maio S,Le,P,et al.Characterization of colloidal structures during intestinal lipolysis using smallangle neutron scattering[J].J Colloid Interface Sci,2017,499:189-201.
[17]Duan RD.Alkaline sphingomyelinase:an old enzyme with novel implications[J].Biochim Biophys Acta,2006,1761(3):281-291.
[18]Duan RD,Hindorf U,Cheng Y,et al.Changes of activity and isoforms of alkaline sphingomyelinase(nucleotide pyrophosphatase phosphodiesterase 7)in bile from patients undergoing endoscopic retrograde cholangiopancreatography[J].BMC Gastroenterol,2014,14:138.
[19]Khan SA,Thomas HC,Davidson BR.et al.Cholangiocarcinoma[J].Lancet,2005,366(9493):1303-1314.
[20]Reddy SB,Patel T.Current approaches to the diagnosis and treatment of cholangiocarcinoma[J].Curr Gastroenterol Rep,2006,8(1):30-37.
[21]Liu JJ,Nilsson A,Duan RD.In vitro effects of fat,FA,and cholesterol on sphingomyelin hydrolysis induced by rat intestinal alkaline sphingomyelinase[J].Lipids,2002,37(5):469-474.
[22]Zhang Y,Cheng Y,Hansen GH,et al.Crucial role of alkaline sphingomyelinase in sphingomyelin digestion:a study on enzyme knockout mice[J].J Lipid Res,2010,52(4):771-781.
[23]Maceyka M,Spiegel S.Sphingolipid metabolites in inflammatory disease[J].Nature,2014,510(7503):58-67.
[24]Foersch S,Waldner MJ,Neurath MF.Colitis and colorectal cancer[J].Dig Dis,2012,30(5):469-476.
[25]Chen Y,Zhang P,Xu SC,et al.Enhanced colonic tumorigenesis in alkaline sphingomyelinase(NPP7)knockout mice[J].Mol Cancer Ther,2014,14(1):259-267.
[2]Gorelik A,Liu F,Illes K,et al.Crystal Structure of the Human Alkaline Sphingomyelinase Provides Insights into Substrate Recognition[J].J Biol Chem,2017,292(17):7087-7094.
[3]Parrill AL,Wanjala IW,Pham,TC,et al.Computational identification and experimental characterization of substrate binding determinants of nucleotide pyrophosphatase/phosphodiesterase 7[J].BMC Biochem,2011,12:65.
[4]Maldonado-Valderrama J,Wilde P,Macierzanka A,et al.The role of bile salts in digestion[J].Adv Colloid Interface Sci,2011,165(1):36-46.
[5]Bienias K,Fiedorowicz A,Sadowska A,et al.Regulation of sphingomyelin metabolism[J].Pharmacol Rep,2016,68(3):570-581.
[6]Airola MV,Allen WJ,Pulkoski-Gross MJ,et al.Structural Basis for Ceramide Recognition and Hydrolysis by Human Neutral Ceramidase[J].Structure,2015,23(8):1482-1491.
[7]Duan RD,Nilsson A.Metabolism of sphingolipids in the gut and its relation to inflammation and cancer development[J].Prog Lipid Res,2008,48(1):62-72.
[8]Nilsson A,Duan RD.Absorption and lipoprotein transport of sphingomyelin[J].J Lipid Res,2005,47(1):154-171.
[9]Keune WJ,Hausmann J,Bolier R,et al.Steroid binding to Autotaxin links bile salts and lysophosphatidic acid signaling[J].Nat Commun,2016,7:11248.
[10]NilssonA.Role of Sphingolipids in Infant Gut Health and Immunity[J].J Pediatr,2016,173 Suppl:S53-S59.
[11]Nyberg L,Duan RD,Nilsson A.A mutual inhibitory effect on absorption of sphingomyelin and cholesterol[J].J Nutr Biochem,2000,11(5):244-249.
[12]Ohlsson L,Hertervig E,J?nsson BA,et al.Sphingolipids in human ileostomy content after meals containing milk sphingomyelin[J].Am J Clin Nutr,2010,91(3):672-678.
[13]Feng D,Ohlsson L,Ling W,et al.Generating ceramide from sphingomyelin by alkaline sphingomyelinase in the gut enhances sphingomyelin-induced inhibition of cholesterol uptake in Caco-2 cells[J].Dig Dis Sci,2010,55(12):3377-3383.
[14]Zhang P,Chen Y,Cheng Y,et al.Alkaline sphingomyelinase(NPP7)promotes cholesterol absorption by affecting sphingomyelin levels in the gut:A study with NPP7knockout mice[J].Am J Physiol Gastrointest Liver Physiol,2014,306(10):G903-908.
[15]Venuti E,Shishmarev D,Kuchel PW,et al.Bile salt stimulated lipase:Inhibition by phospholipids and relief by phospholipase A2[J].J Cyst Fibros,2017,16(6):763-770.
[16]Rezhdo O,Di Maio S,Le,P,et al.Characterization of colloidal structures during intestinal lipolysis using smallangle neutron scattering[J].J Colloid Interface Sci,2017,499:189-201.
[17]Duan RD.Alkaline sphingomyelinase:an old enzyme with novel implications[J].Biochim Biophys Acta,2006,1761(3):281-291.
[18]Duan RD,Hindorf U,Cheng Y,et al.Changes of activity and isoforms of alkaline sphingomyelinase(nucleotide pyrophosphatase phosphodiesterase 7)in bile from patients undergoing endoscopic retrograde cholangiopancreatography[J].BMC Gastroenterol,2014,14:138.
[19]Khan SA,Thomas HC,Davidson BR.et al.Cholangiocarcinoma[J].Lancet,2005,366(9493):1303-1314.
[20]Reddy SB,Patel T.Current approaches to the diagnosis and treatment of cholangiocarcinoma[J].Curr Gastroenterol Rep,2006,8(1):30-37.
[21]Liu JJ,Nilsson A,Duan RD.In vitro effects of fat,FA,and cholesterol on sphingomyelin hydrolysis induced by rat intestinal alkaline sphingomyelinase[J].Lipids,2002,37(5):469-474.
[22]Zhang Y,Cheng Y,Hansen GH,et al.Crucial role of alkaline sphingomyelinase in sphingomyelin digestion:a study on enzyme knockout mice[J].J Lipid Res,2010,52(4):771-781.
[23]Maceyka M,Spiegel S.Sphingolipid metabolites in inflammatory disease[J].Nature,2014,510(7503):58-67.
[24]Foersch S,Waldner MJ,Neurath MF.Colitis and colorectal cancer[J].Dig Dis,2012,30(5):469-476.
[25]Chen Y,Zhang P,Xu SC,et al.Enhanced colonic tumorigenesis in alkaline sphingomyelinase(NPP7)knockout mice[J].Mol Cancer Ther,2014,14(1):259-267.