Abstract:
:We previously observed that gangliosides GM2, GM1, and GM3 inhibit Ca2+-uptake via the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) in neurons and in brain microsomes. We now systematically examine the effect of various gangliosides and their analogs on Ca2+-uptake via SERCA and demonstrate that an exposed carboxyl group on the ganglioside sialic acid residue is required for inhibition. Thus, asialo-GM2 and asialo-GM1 have no inhibitory effect, and modifications of the carboxyl group of GM1 and GM2 into a hydroxymethyl residue (CH2OH), a methyl ester (COOCH3) or a taurine-conjugated amide (CONHCH2CH2SO3H) drastically diminish their inhibitory activities. We also demonstrate that the saccharides must be attached to a ceramide backbone in order to inhibit SERCA as the ceramide-free ganglioside saccharides only inhibit SERCA to a minimal extent. Finally, we attempted to use the ceramide-free ganglioside saccharides to antagonize the effects of the gangliosides on SERCA; although some reversal was observed, the inhibitory effects of the gangliosides were not completely abolished.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Ginzburg L,Li SC,Li YT,Futerman AHdoi
10.1111/j.1471-4159.2007.04983.xsubject
Has Abstractpub_date
2008-01-01 00:00:00pages
140-6issue
1eissn
0022-3042issn
1471-4159pii
JNC4983journal_volume
104pub_type
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journal_title:Journal of neurochemistry
pub_type: 杂志文章,多中心研究
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journal_title:Journal of neurochemistry
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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