Lysosome-mediated degradation of a distinct pool of lipid droplets during hepatic stellate cell activation.
作者： Maidina Tuohetahuntila , Martijn R. Molenaar , Bart Spee , Jos F. Brouwers , Richard Wubbolts
关键词:
摘要: Activation of hepatic stellate cells (HSCs) is a critical step in the development liver fibrosis. During activation, HSCs lose their lipid droplets (LDs) containing triacylglycerols (TAGs), cholesteryl esters, and retinyl esters (REs). We previously provided evidence for presence two distinct LD pools, preexisting dynamic pool. Here we investigate mechanisms neutral metabolism To involvement lysosomal degradation lipids, studied effect lalistat, specific acid lipase (LAL/Lipa) inhibitor on during activation vitro. The LAL increased levels TAG, ester, RE both rat mouse HSCs. Lalistat was less potent inhibiting newly synthesized TAG species as compared with more general orlistat. also induced RE-containing LDs an acidic compartment. However, targeted deletion Lipa gene mice decreased RE, most likely result gradual disappearance livers Lipa−/− mice. partially inhibited induction marker α-smooth muscle actin (α-SMA) Our data suggest that LAL/Lipa involved pool inhibition this pathway attenuates HSC activation.
sci-hub.se 参考文章(42)
Lisa Riccalton-Banks, Rena Bhandari, Jeffrey Fry, Kevin M Shakesheff, A simple method for the simultaneous isolation of stellate cells and hepatocytes from rat liver tissue. Molecular and Cellular Biochemistry. ,vol. 248, pp. 97- 102 ,(2003) , 10.1023/A:1024184826728
R Blomhoff, W Eskild, G M Kindberg, K Prydz, T Berg, Intracellular transport of endocytosed chylomicron [3H]retinyl ester in rat liver parenchymal cells. Evidence for translocation of a [3H]retinoid from endosomes to endoplasmic reticulum. Journal of Biological Chemistry. ,vol. 260, pp. 13566- 13570 ,(1985) , 10.1016/S0021-9258(17)38760-4
Allan P. Long, Anna K. Manneschmidt, Bobby VerBrugge, Mary R. Dortch, Steven C. Minkin, Keith E. Prater, John P. Biggerstaff, John R. Dunlap, Paul Dalhaimer, Lipid droplet de novo formation and fission are linked to the cell cycle in fission yeast. Traffic. ,vol. 13, pp. 705- 714 ,(2012) , 10.1111/J.1600-0854.2012.01339.X
Bengt Borgström, Mode of action of tetrahydrolipstatin: a derivative of the naturally occurring lipase inhibitor lipstatin Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. ,vol. 962, pp. 308- 316 ,(1988) , 10.1016/0005-2760(88)90260-3
Mireille Ouimet, Vivian Franklin, Esther Mak, Xianghai Liao, Ira Tabas, Yves L. Marcel, Autophagy Regulates Cholesterol Efflux from Macrophage Foam Cells via Lysosomal Acid Lipase Cell Metabolism. ,vol. 13, pp. 655- 667 ,(2011) , 10.1016/J.CMET.2011.03.023
Kouta Yamamoto, Kazuo Ogawa, Fine structure and cytochemistry of lysosomes in the Ito cells of the rat liver. Cell and Tissue Research. ,vol. 233, pp. 45- 57 ,(1983) , 10.1007/BF00222231
Anton I. Rosenbaum, Casey C. Cosner, Christopher J. Mariani, Frederick R. Maxfield, Olaf Wiest, Paul Helquist, Thiadiazole Carbamates: Potent Inhibitors of Lysosomal Acid Lipase and Potential Niemann−Pick Type C Disease Therapeutics Journal of Medicinal Chemistry. ,vol. 53, pp. 5281- 5289 ,(2010) , 10.1021/JM100499S
Noboru Mizushima, Yoshinori Ohsumi, Tamotsu Yoshimori, Autophagosome formation in mammalian cells. Cell Structure and Function. ,vol. 27, pp. 421- 429 ,(2002) , 10.1247/CSF.27.421
William S. Blaner, Sheila M. O'Byrne, Nuttaporn Wongsiriroj, Johannes Kluwe, Diana M. D'Ambrosio, Hongfeng Jiang, Robert F. Schwabe, Elizabeth M.C. Hillman, Roseann Piantedosi, Jenny Libien, Hepatic stellate cell lipid droplets: A specialized lipid droplet for retinoid storage Biochimica et Biophysica Acta. ,vol. 1791, pp. 467- 473 ,(2009) , 10.1016/J.BBALIP.2008.11.001
Muriel Mercier, Anne Forget, Pascal Grolier, Véronique Azais-Braesco, Hydrolysis of retinyl esters in rat liver. Description of a lysosomal activity Biochimica et Biophysica Acta. ,vol. 1212, pp. 176- 182 ,(1994) , 10.1016/0005-2760(94)90251-8