Differential effect of ganglioside GM1 on rat brain phosphoproteins: potentiation and inhibition of protein phosphorylation regulated by calcium/calmodulin and calcium/phospholipid‐dependent protein kinases

Cimino, Mauro; Benfenati, Fabio; Farabegoli, C.; Cattabeni, F.; Fuxé, Kjell; Agnati, Luigi F.; Toffano, G.

doi:10.1111/j.1748-1716.1987.tb08143.x

Cited by 29 publications

(6 citation statements)

References 27 publications

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“…The effect of in vitro addition of either GA mixtures or individual GAs on protein phosphorylation in cells and subcellular fractions has been reported to be inhibitory or stimulatory depending on the particular preparation (41)(42)(43). In brain, GAs may directly activate GA-stimulated protein kinase (44) or serve as a negative effector on the receptormediated translocation of protein kinase C (42).…”

Section: Discussionmentioning

confidence: 99%

Correction of Altered Metabolic Activities in Sciatic Nerves of Streptozocin-Induced Diabetic Rats: Effect of Ganglioside Treatment

Bianchi

Berti‐Mattera²,

Fiori³

et al. 1990

Diabetes

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The effect of ganglioside administration to nondiabetic and streptozocin-induced diabetic rats on sciatic nerve Na(+)-K(+)-ATPase, polyphosphoinositide (PPI) turnover, and protein phosphorylation was investigated. Gangliosides were injected (10 mg/kg body wt i.p.) for 10 or 30 days beginning 20 days after induction of diabetes. Na(+)-K(+)-ATPase activity was reduced nearly 50% in diabetic nerve and was restored to normal by both ganglioside treatments. The elevated levels of fructose and sorbitol and depressed content of myoinositol in diabetic nerve were unaffected by 30 days of ganglioside treatment, indicating that the restoration of Na(+)-K(+)-ATPase activity is not dependent on normal concentrations of these compounds. In the same nerves, 32P incorporation into phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-phosphate increased 73-76 and 39-53%, respectively, in diabetic compared with nondiabetic tissue. Ganglioside administration abolished the elevated labeling of PPIs after 30 days but was ineffective after only 10 days. Neither ganglioside regimen was able to reverse enhanced phosphorylation of the major peripheral nerve myelin protein P0. The finding that gangliosides can more quickly correct the effects of diabetes on Na(+)-K(+)-ATPase activity than on PPI turnover suggests that the mechanisms underlying these two phenomena are not closely related and are distinct from the sequence of events responsible for altered myelin protein phosphorylation.

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Section: Discussionmentioning

confidence: 99%

Correction of Altered Metabolic Activities in Sciatic Nerves of Streptozocin-Induced Diabetic Rats: Effect of Ganglioside Treatment

Bianchi

Berti‐Mattera²,

Fiori³

et al. 1990

Diabetes

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“…Sphingosine inhibits PKC activity when lysine-rich histone (histone H1), one of the most useful exogenous substrates, is used as the substrate [6]; however, in the case of endogenous protein phosphorylation, sphingosine acts as inhibitors or stimulators for individual substrates [9,26]. Moreover, gangliosides have dual effects on phosphorylation of various PKC substrates in rat brain [3] and cow mammary gland [11,12,15,16]. Sulfatide, on the other hand, appears to inhibit PKC activity when the histone is included in the assay mixture [32].…”

Section: +mentioning

confidence: 99%

Inhibition by Sulfatide of 21-kDa Protein Phosphorylation by Protein Kinase C in Cow Mammary Gland and its Reversal by Phosphatidylserine

Katoh

2004

The Journal of Veterinary Medical Science

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ABSTRACT. The effect of sulfatide, a sulfated sphingolipid, on phosphorylation of endogenous proteins by protein kinase C (PKC) was examined in cow mammary gland. Several proteins, including 21-kDa, 43-kDa and 56-kDa proteins in the cytosolic fraction, were f ound to be substrates for PKC by phosphorylation in the absence or presence of the cofactors 1-oleoyl-2-acetyl-sn-glycerol (OAG), phosphatidylserine (PS) and Ca 2+. Sulfatide inhibited the 21-kDa phosphorylation, whereas it enhanced the 56-kDa and 43-kDa phosphorylation. Experiments were then conducted to examine whether other sphingolipids, including sphingosine, dihydrosphingosine, ceramides, ga lactocerebrosides, psychosine and sphingomyelin, modulated phosphorylation of the PKC substrates. Sphingosine, dihydrosphingosine and psychosine did not inhibit the 21-kDa phosphorylation; however, they enhanced the 56-kDa and 43-kDa phosphorylation. Ceramides, galactocerebrosides and sphingomyelin did not inhibit the 21-kDa or enhance the 56-kDa and 43-kDa phosphorylation. The inhibition by sulfatide of the 21-kDa phosphorylation was reversed by excess addition of PS, but not by OAG or Ca 2+; whereas the enhancement by sulfatide, as well as sphingosine, dihydrosphingosine and psychosine, of 56-kDa and 43-kDa phosphorylation was not affected by PS, OAG or Ca 2+. It is suggested that sulfatide is involved in the regulation of PKC-dependent phosphorylation by modulating the association of PKC substrates, in particular the 21-kDa protein, with membrane phospholipids in cow mammary gland. KEY WORDS: cattle, mammary gland, protein kinase C, sphingolipids, sulfatide.J. Vet. Med. Sci. 66 (7): [821][822][823][824][825] 2004 Sphingolipids, a major class of membrane lipids, consist of a hydrophobic portion, called ceramide, which contains a mixture of fatty acids that are amide-linked to sphingosine or other related long-chain aliphatic amines (sphingoid bases), and a hydrophilic portion (polar head group) [30]. Except for a few cases such as phosphorylcholine in sphingomyelin, most of the polar head groups are carbohydrates, and glycosphingolipids include neutral lipids (galactocerebrosides), and acidic lipids, which contain sialic acid residu es (gangliosides), or sulfate mo noester grou ps (sulfatides). Sulfatide is well known to be the causal factor for metachromatic leukodystrophy in the central and peripheral nervous systems [31].Protein kinase C (PKC) is an enzyme activated by diacylglycerols, phospholipids, in particular phosphatidylserine (PS), and Ca 2+ , and exerts a wide variety of cellular functions by phosphorylating serine and threonine residues of various enzymes and proteins [13,20,23]. Sphingolipids are modulators for PKC [5]. Sphingosine inhibits PKC activity when lysine-rich histone (histone H1), one of the most useful exogenous substrates, is used as the substrate [6]; however, in the case of endogenous protein phosphorylation, sphingosine acts as inhibitors or stimulators for individual substrates [9,26]. Moreover, gangliosides have dual effects on ...

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“…It is also interesting that as one might have anticipated, a psychotropic drug such as IMI inhibits brain PKC more effectively than skin PKC. A wide variety of PKC substrates have been identified in a large number of tissues [34][35][36][37], Among these. p80, p20 and p l4 in brain [35], and p38 and p33 in bovine thyroid [37] are subject to inhibition by the antidepressant, TFP, while p40 and p34 in mouse epidermis are inhibited by CPZ [34], This communication demonstrates that a number of skin proteins phosphorylated by PKC are targets for inhibition by a variety of psychotropic agents.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Skin Protein Kinase C by Psychotropic Drugs

Vaitla

Roshani

Holian

et al. 1997

Skin Pharmacol Physiol

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Lipid-soluble psychotropics are often used to treat skin diseases with psychosomatic indications. Although these drugs are known to exert their effects through the central nervous system, relatively little is known about their mechanism of action in skin. In this communication, several lipid-soluble psychotropic drugs have been examined for their ability to inhibit protein kinase C (PKC)-catalyzed phosphorylation of exogenous substrates and endogenous skin proteins. Phosphorylation of three discrete skin protein substrates at 64, 42 and 28 kDa and a group crowded together at 15-18 kDa was prevented by the antidepressants/antipsychotics. Inhibition was more pronounced in a phospholipid (PL) dependent system, but both drug-PL and drug-PKC interactions seem to be important in the mechanism of action of these drugs. In addition to the tricyclic nucleus, the propanamine side chain or its N-methyl form may influence the interaction of these drugs with PKC and its substrate(s). Chlorpromazine, imipramine, fluoxetine, doxepin, amitriptyline and hydroxyzine used in the practice of dermatology may exert their therapeutic effects by modulating skin PKC activity.

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Differential effect of ganglioside GM1 on rat brain phosphoproteins: potentiation and inhibition of protein phosphorylation regulated by calcium/calmodulin and calcium/phospholipid‐dependent protein kinases

Cited by 29 publications

References 27 publications

Correction of Altered Metabolic Activities in Sciatic Nerves of Streptozocin-Induced Diabetic Rats: Effect of Ganglioside Treatment

Correction of Altered Metabolic Activities in Sciatic Nerves of Streptozocin-Induced Diabetic Rats: Effect of Ganglioside Treatment

Inhibition by Sulfatide of 21-kDa Protein Phosphorylation by Protein Kinase C in Cow Mammary Gland and its Reversal by Phosphatidylserine

Inhibition of Skin Protein Kinase C by Psychotropic Drugs

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