Lactosylceramide contributes to mitochondrial dysfunction in diabetes.

Journal of Lipid Research
Sergei A NovgorodovTatyana I Gudz

Abstract

Sphingolipids have been implicated as key mediators of cell-stress responses and effectors of mitochondrial function. To investigate potential mechanisms underlying mitochondrial dysfunction, an important contributor to diabetic cardiomyopathy, we examined alterations of cardiac sphingolipid metabolism in a mouse with streptozotocin-induced type 1 diabetes. Diabetes increased expression of desaturase 1, (dihydro)ceramide synthase (CerS)2, serine palmitoyl transferase 1, and the rate of ceramide formation by mitochondria-resident CerSs, indicating an activation of ceramide biosynthesis. However, the lack of an increase in mitochondrial ceramide suggests concomitant upregulation of ceramide-metabolizing pathways. Elevated levels of lactosylceramide, one of the initial products in the formation of glycosphingolipids were accompanied with decreased respiration and calcium retention capacity (CRC) in mitochondria from diabetic heart tissue. In baseline mitochondria, lactosylceramide potently suppressed state 3 respiration and decreased CRC, suggesting lactosylceramide as the primary sphingolipid responsible for mitochondrial defects in diabetic hearts. Moreover, knocking down the neutral ceramidase (NCDase) resulted in an increase i...Continue Reading

References

Aug 7, 1999·The Journal of Biological Chemistry·B S Kristal, A M Brown
Apr 27, 2000·The Journal of Biological Chemistry·S El BawabY A Hannun
Apr 27, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·C García-RuizJ C Fernández-Checa
Aug 10, 2002·American Journal of Physiology. Endocrinology and Metabolism·Joost J F P LuikenArend Bonen
Jul 29, 2004·American Journal of Physiology. Endocrinology and Metabolism·Xia ShenPaul N Epstein
Feb 22, 2005·The Journal of Biological Chemistry·Sergei A NovgorodovLina M Obeid
Apr 6, 2005·Biochemistry. Biokhimii︠a︡·A Yu AndreyevA A Starkov
Dec 29, 2005·The Journal of Biological Chemistry·Mari KonoRichard L Proia
Mar 8, 2006·Free Radical Biology & Medicine·Ossama M LashinAndrea M P Romani
May 27, 2006·Mitochondrion·Sidi Mohamed HassounRemi Neviere
Jul 11, 2006·Methods : a Companion to Methods in Enzymology·Jacek BielawskiAlicja Bielawska
Jul 20, 2006·American Journal of Physiology. Endocrinology and Metabolism·Sarah M TurpinMatthew J Watt
Jul 21, 2006·American Journal of Physiology. Cell Physiology·Lamar K GerberMohammed A Matlib
Sep 20, 2006·The Journal of Cell Biology·György CsordásGyörgy Hajnóczky
Jun 15, 2007·Cellular and Molecular Life Sciences : CMLS·S Lahiri, A H Futerman
Jul 5, 2007·The Journal of Biological Chemistry·Jin YuTatyana I Gudz
Jan 25, 2008·Nature Reviews. Molecular Cell Biology·Yusuf A Hannun, Lina M Obeid
Jun 3, 2008·Journal of Lipid Research·Tae-Sik ParkIra J Goldberg
Jul 4, 2008·The Journal of Biological Chemistry·Sergei A NovgorodovLina M Obeid
Oct 11, 2008·Journal of Lipid Research·Robert K YuMakoto Yanagisawa
Dec 9, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Erinne R DabkowskiJohn M Hollander
Dec 17, 2008·Biochimica Et Biophysica Acta·Bodil Westerlund, J Peter Slotte
Feb 28, 2009·Journal of Cardiovascular Pharmacology·Sergei A Novgorodov, Tatyana I Gudz
May 12, 2009·The Journal of Biological Chemistry·Takeshi YabuMichiaki Yamashita
Sep 4, 2009·Disease Models & Mechanisms·Heiko Bugger, E Dale Abel

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Citations

Apr 5, 2017·Journal of Molecular Endocrinology·Rebecca H RitchieAnna C Calkin
Jul 7, 2016·American Journal of Physiology. Endocrinology and Metabolism·Hanin AburasaynJohn R Ussher
Aug 21, 2019·Micromachines·Qian FengBenoît Kornmann
Jun 25, 2017·Clinical Science·Keith DadsonFilio Billia
Oct 9, 2019·International Journal of Molecular Sciences·Jae Ho LeeKwang-Hee Bae
Dec 7, 2019·Clinical Science·Chayodom ManeechoteNipon Chattipakorn
Nov 12, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Brittany A LawL Ashley Cowart
Jun 3, 2020·International Journal of Molecular Sciences·Yan LevitskyDenis A Proshlyakov
Jul 18, 2020·Animal Science Journal = Nihon Chikusan Gakkaihō·Mi-Ryung ParkSeong-Keun Cho
May 16, 2018·PeerJ·Jannatul FerdouseHiroshi Kitagaki
Jul 18, 2020·International Journal of Molecular Sciences·Humna BhaganiAli H Eid
Mar 29, 2019·Emerging Topics in Life Sciences·Wyatt W YueGustavo A Bezerra
Sep 20, 2020·Journal of Lipid Research·M Victoria SimonNawajes Mandal
Feb 5, 2021·Circulation Research·Ioannis D KyriazisKonstantinos Drosatos
Feb 29, 2020·Biochemical and Biophysical Research Communications·Subroto ChatterjeeSean A Campbell
Feb 9, 2021·Journal of Lipid Research·Simon M VictoriaMandal Nawajes
Feb 23, 2021·Diabetic Medicine : a Journal of the British Diabetic Association·Meghana D GadgilDavid M Herrington
Mar 7, 2021·International Journal of Molecular Sciences·Subroto ChatterjeeWendy Li
Sep 18, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jiung-Pang HuangLi-Man Hung
Nov 2, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marwa ZafarullahFlora Tassone

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