TY - JOUR
T1 - The Yin and Yang of lactosylceramide metabolism
T2 - Implications in cell function
AU - Chatterjee, Subroto
AU - Pandey, Ambarish
N1 - Funding Information:
We would like to thank several of our colleagues for sharing their knowledge on LacCer with us. They are Drs. Nupur Ghosh, Anil Bhunia, Anotnina Kolmakova, Sergio Martin, Nieshia Williams, Peter Kwiterovich, Rajesh Mohan, NanLing Gong, Heming Wei, Sanaul Cowdhury, Dimitry Mukhin, Sraboney Dey, Avi Mazumdar, Toshi Arai, Gregory Bulkley, Pabodh Gupta, Yener Erozan, Grover Hutchins, Carl Alving, Jim Rifkind, Chandrashekhar Balgopalkrishna, Judy Berliner, G. Subbangounder and Wanda Shi. The support from NIH RO-1 DK 31722, PO-1-HL 47212, American Heart Association, and Johns Hopkins University Institutional support is gratefully acknowledged.
PY - 2008/3
Y1 - 2008/3
N2 - Although lactosylceramide (LacCer) plays a pivotal role in the biosynthesis of nearly all the major glycosphingolipids, its function in regulating cellular function has begun to emerge only recently. Our current opinion is that several physiologically critical molecules such as modified/oxidized LDL, growth factors, pro-inflammatory cytokines and fluid shear stress converge upon and activate lactosylceramide synthase to generate LacCer. In turn, LacCer activates an "oxygen-sensitive" signaling pathway involving superoxides, nitric oxide, p21 Ras GTP loading, kinase cascade, PI3kinase/Akt activation, nuclear factor up-regulation ultimately contributing to phenotypic changes such as cell proliferation, adhesion, migration and angiogenesis. Since dys-regulation of such phenotypic changes constitute a hallmark in several diseases of the cardiovascular system, proliferative disorders such as cancer, polycystic kidney disease and inflammatory diseases, LacCer synthase and LacCer provide novel targets for the development of therapeutics aimed at these health conditions.
AB - Although lactosylceramide (LacCer) plays a pivotal role in the biosynthesis of nearly all the major glycosphingolipids, its function in regulating cellular function has begun to emerge only recently. Our current opinion is that several physiologically critical molecules such as modified/oxidized LDL, growth factors, pro-inflammatory cytokines and fluid shear stress converge upon and activate lactosylceramide synthase to generate LacCer. In turn, LacCer activates an "oxygen-sensitive" signaling pathway involving superoxides, nitric oxide, p21 Ras GTP loading, kinase cascade, PI3kinase/Akt activation, nuclear factor up-regulation ultimately contributing to phenotypic changes such as cell proliferation, adhesion, migration and angiogenesis. Since dys-regulation of such phenotypic changes constitute a hallmark in several diseases of the cardiovascular system, proliferative disorders such as cancer, polycystic kidney disease and inflammatory diseases, LacCer synthase and LacCer provide novel targets for the development of therapeutics aimed at these health conditions.
KW - Angiogenesis
KW - Apoptosis
KW - Cell adhesion
KW - Cell proliferation
KW - Gangliosides
KW - Glycosphingolipids
KW - Lactosylceramide
KW - Signal transduction
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U2 - 10.1016/j.bbagen.2007.08.010
DO - 10.1016/j.bbagen.2007.08.010
M3 - Review article
C2 - 18077097
AN - SCOPUS:40849120250
SN - 0304-4165
VL - 1780
SP - 370
EP - 382
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 3
ER -