Plasmalopsychosine of Human Brain Mimics the Effect of Nerve Growth Factor by Activating Its Receptor Kinase and Mitogen-activated Protein Kinase in PC12 Cells

Sakakura, Chouhei; Igarashi, Yasuyuki; Anand, Jasbir K.; Sadozai, Khalid K.; Hakomori, Sen‐itiroh

doi:10.1074/jbc.271.2.946

Cited by 24 publications

(12 citation statements)

References 42 publications

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“…Studies on modulatory effects, initially observed with GM3 on EGFR tyrosine kinase [1], have been extended to effects of GM1, GD1a, GD1b, and GT1b on platelet-derived growth factor receptor [21,24], GM1 and plasmalopsychosine on nerve growth factor receptor [23,25], and GM3 and sialyl-nLc4 on insulin receptors [22,26]. Therefore, such glycosphingolipid effects can be considered as common in growth factor and hormone receptors, in general (for review see [27,28]).…”

Section: Discussionmentioning

confidence: 99%

Effect of lipid mimetics of GM3 and lyso-GM3 dimer on EGF receptor tyrosine kinase and EGF-induced signal transduction

Haga

Hatanaka

Hakomori

2008

Biochimica et Biophysica Acta (BBA) - General Subjects

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The tyrosine kinase activity associated with epidermal growth factor receptor (EGFR) has been a target in studies of pharmacological reagents to inhibit growth of cancer cells, which are mostly of epidermal origin. Lyso-GM3 dimer showed stronger inhibitory effect on the tyrosine kinase of EGFR than GM3, with minimal cytotoxicity (Y. Murozuka, et al., Glycoconj. J., 24: 551-63, 2007). Synthesis of lipids with sphingosine requires many steps, and the yield is low. Biocombinatory approach overcame this difficulty; however, products required a C 12 aliphatic chain, rather than the sphingosine head group (Y. Murozuka, et al., Chem. Biodivers. 2: 1063-78, 2005). The present study was to clarify the effects of these lipid mimetics of GM3 and lyso-GM3 dimer on EGFR tyrosine kinase activity, and consequent changes of the A431 cell phenotype, as follows. (i) A lipid mimetic of lyso-GM3 dimer showed similar strong inhibitory effect on EGF-induced EGFR tyrosine kinase activity, and similar low cytotoxicity, as the authentic lyso-GM3 dimer. (ii) A lipid mimetic of lyso-GM3 dimer inhibited tyrosine phosphorylation of EGFR or its dimer to a level similar to that of the authentic lyso-GM3 dimer, but more strongly than GM3 or a lipid mimetic of GM3. (iii) Associated with the inhibitory effect of a lipid mimetic of lyso-GM3 dimer on EGF-induced EGFR kinase activity, only Akt kinase activity was significantly inhibited, but kinases associated with other signal transducers were not affected. (iv) The cell cycle of A431 cells, and the effects of GM3 and lipid mimetic of lyso-GM3 dimer, were studied by flow cytometry, measuring the rate of DNA synthesis with propidium iodide. Fetal bovine serum greatly enhanced S phase and G 2 /M phase. Enhanced G 2 /M phase was selectively inhibited by pre-incubation of A431 cells with a lipid mimetic of lyso-GM3 dimer, whereas GM3 had only a minimal effect.

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Section: Discussionmentioning

confidence: 99%

Effect of lipid mimetics of GM3 and lyso-GM3 dimer on EGF receptor tyrosine kinase and EGF-induced signal transduction

Haga

Hatanaka

Hakomori

2008

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…Another example is activation by PLPS of Trk A tyrosine kinase in PC12 cells, leading to enhancement of mitogen-activated protein kinase. This mimics the effect of nerve growth factor, because withdrawal of PLPS induces apoptosis (7). PLPS weakly inhibits PKC, whereas psychosine strongly inhibits PKC (3).…”

Section: Discussionmentioning

confidence: 99%

“…PLPS has the novel effect of inducing signal transduction in neuronal cells, particularly neuritogenesis in PC12 cells without addition of nerve growth factor; i.e. PLPS mimics the effect of nerve growth factor (7). During previous studies, we noticed the presence of cationic lipids having slower TLC migration rate than PLPS in human brain (3).…”

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confidence: 99%

A Novel Plasmal Conjugate to Glycerol and Psychosine (“Glyceroplasmalopsychosine”)

Hikita

Tadano-Aritomi

Iida-Tanaka

et al. 2001

Journal of Biological Chemistry

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A novel plasmal conjugate of glycosphingolipid having cationic lipid properties was isolated from the white matter of bovine brain. Linkage analysis of galactosyl residue by methylation, liquid secondary ion, and electrospray ionization mass spectrometry of intact and methylated derivatives, and by 1 H-and 13 C-NMR spectroscopy, identified the structure unambiguously as an O-acetal conjugate of plasmal to the primary hydroxyl group of glycerol and to the 6-hydroxyl group of galactosyl residue of ␤-galactosyl 131 sphingosine (psychosine). This novel compound is hereby termed "glyceroplasmalopsychosine"; its structure is shown below.Long chain aldehydes, hexadecanal and octadecanal, with or without an olefinic double bond, are collectively called plasmal, and are known as a common component of two classes of lipid conjugates, described as follows: (i) the classically well-established phospholipid plasmalogen (1, 2), in which plasmal is conjugated as O-alk-1-enyl (vinyl ether) group to one of the hydroxyl groups of glycerol in phosphatidylethanolamine or phosphatidylcholine 1 ; (ii) the recently found novel type of glycosphingolipid (GSL) 2 in which a plasmal is conjugated to two hydroxyl groups of the galactosyl residue of galactosylsphingosine (psychosine) or galactosylceramide through cyclic acetal linkage; these were originally isolated from human brain white matter and are termed, respectively, plasmalopsychosine (PLPS) and plasmalocerebroside. Depending on the position of hydroxyl group involved in acetal linkages, 3,4-and 4,6-cyclic plasmal conjugates of PLPS and plasmalocerebroside are termed, respectively, PLPS A or B (3), and plasmalocerebroside A or B (4). More recently, a GSL having the same structure as plasmalocerebroside B (4,6-cyclic acetal) was isolated from equine brain. The orientation of the acetal chain linked to galactosyl residue through asymmetric carbon 1 of plasmal was identified as "endo" type, initially on model plasmal conjugate of methyl-␤-galactoside (45), subsequently on 4,6-plasmalocerebroside (5). A similar 4,6-cyclic acetal conjugate of plasmal to galactosyl alkylglyceride was isolated and characterized (6). All these conjugates are characterized by typical aldehyde reaction (e.g. oxidizing Schiff's reagent to give red color, after brief acid treatment). Among them, only PLPS shows cationic properties, and can be isolated by cation-exchange chromatography on carboxymethyl (CM)-Sephadex column in organic solvent, because of its free amino group at Sph residue. Cationic lipids are rare in animal cells and tissues (see "Discussion"). PLPS has the novel effect of inducing signal transduction in neuronal cells, particularly neuritogenesis in PC12 cells without addition of nerve growth factor; i.e. PLPS mimics the effect of nerve growth factor (7). During previous studies, we noticed the presence of cationic lipids having slower TLC migration rate than PLPS in human brain (3). We therefore undertook further systematic study of cationic lipids with plasmal conjugate in bovine brain.Durin...

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“…(v) Neuronal cell function in brain or central nervous system is maintained by nerve growth factor (NGF) receptor or brain-derived growth factor (BDGF) receptor, whose functions are modulated by surrounding gangliosides or GSLs in glycosynapse (Mutoh et al 1995, Sakakura et al 1996, Prinetti et al 1999.…”

Section: Cell Social Function and Glycosynapsementioning

confidence: 99%

Glycosynapses: microdomains controlling carbohydrate-dependent cell adhesion and signaling

Hakomori

2004

An. Acad. Bras. Ciênc.

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The concept of microdomains in plasma membranes was developed over two decades, following observation of polarity of membrane based on clustering of specific membrane components. Microdomains involved in carbohydrate-dependent cell adhesion with concurrent signal transduction that affect cellular phenotype are termed "glycosynapse". Three types of glycosynapse have been distinguished: "type 1" having glycosphingolipid associated with signal transducers (small G-proteins, cSrc, Src family kinases) and proteolipids; "type 2" having O-linked mucin-type glycoprotein associated with Src family kinases; and "type 3" having N-linked integrin receptor complexed with tetraspanin and ganglioside. Different cell types are characterized by presence of specific types of glycosynapse or their combinations, whose adhesion induces signal transduction to either facilitate or inhibit signaling. E.g., signaling through type 3 glycosynapse inhibits cell motility and differentiation. Glycosynapses are distinct from classically-known microdomains termed "caveolae", "caveolar membrane", or more recently "lipid raft", which are not involved in carbohydrate-dependent cell adhesion. Type 1 and type 3 glycosynapses are resistant to cholesterol-binding reagents, whereas structure and function of "caveolar membrane" or "lipid raft" are disrupted by these reagents. Various data indicate a functional role of glycosynapses during differentiation, development, and oncogenic transformation.

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Plasmalopsychosine of Human Brain Mimics the Effect of Nerve Growth Factor by Activating Its Receptor Kinase and Mitogen-activated Protein Kinase in PC12 Cells

Cited by 24 publications

References 42 publications

Effect of lipid mimetics of GM3 and lyso-GM3 dimer on EGF receptor tyrosine kinase and EGF-induced signal transduction

Effect of lipid mimetics of GM3 and lyso-GM3 dimer on EGF receptor tyrosine kinase and EGF-induced signal transduction

A Novel Plasmal Conjugate to Glycerol and Psychosine (“Glyceroplasmalopsychosine”)

Glycosynapses: microdomains controlling carbohydrate-dependent cell adhesion and signaling

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