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Papers by Diwakar Deshmukh
Lipids, 1977
The hydrogen belts of membranes are defined as the regions consisting of hydrogen bond acceptors,... more The hydrogen belts of membranes are defined as the regions consisting of hydrogen bond acceptors, i.e., the C=O groups of glycero- and sphingolipids, and hydrogen bond donors, i.e., cholesterol-OH, sphingolipid-OH, proteins, and water. Lipid-lipid hydrogen bonding in these belts has been suggested. The connection of such hypothetical bonding with the condensation effect, i.e., the apparent reduction of surface area occupied by phospholipids in mixed monolayers with cholesterol, has been tested with lipids possissing and lacking C=O groups: diester, diether, and dialkyl phosphatidylcholine, and analogous polyoxyethylene diglycerides. Condensation by cholesterol was observed for all lipids. Consequently, the hypothetical lipid-C=O-cholesterol hydrogen bonding is not a prerequisite for the condensation effect.
Progress in brain research, 1973
Neurochemical Research, 1981
When unilamellar "stable" liposomes composed of a dialkyl analog of phosphatidy... more When unilamellar "stable" liposomes composed of a dialkyl analog of phosphatidylcholine, tetradecyloctadec-11-eno(1)phosphocholine (dialkyl-PC), plus cholesterol at 1:1 molar ratio, and a trace of [3H]dialkyl-PC were injected into the vitreous of the rabbit eye, macrophage infiltration and phagocytosis of lipid were observed in retina including the epiretinal myelinated nerve fiber bundles, with no other neurotoxic effects. Little or no incorporation of [3h]dialkyl-PC was observed in the distal tissues of the optic system. With "labile" vesicles composed of egg lecithin, trace amounts of [3H]dialkyl-PC, and phosphatidic acid, no morphological changes occurred. After a lag of more than 7 days [3H]dialkyl-PC appeared in superior colliculus, indicating axonal transport of the lipid in an anterograde direction. Experiments with submandibular and parotid gland indicated retrograde transport of the lipid. The data do not suggest axonal transport of intact (stable) liposomes, but suggest that intact phospholipid molecules can be axonally transported.
Neurochemical Research, 1980
We describe an attempt to incorporate a metabolically inert phospholipid analog into animal membr... more We describe an attempt to incorporate a metabolically inert phospholipid analog into animal membranes, especially myelin, in vivo, with the view of eventual long-term membrane modification or membrane engineering. A sonicated suspension of a mixture of [14C]phosphatidylcholine and its dialkyl analog, [3H] tetradecyloctadecano(1)phosphocholine, was injected into the brain of weanling rats. Samples were counted of whole brain, myelin, liver, and carcass, at intervals from 1 to 63 days, and the composition of the extracted lipid was determined by thin-layer chromatography. Both lipid labels were found to be cleared from the body at similar rates, but while phosphatidylcholine was metabolized within a day, with the label appearing mainly in the phosphatidylethanolamine fraction and in nonpolar lipids, the dialkylphosphatidylcholine remained intact, with retention in myelin of a small but almost constant amount for a month. Ways will have to be found to enhance uptake of the lipids by the brain.
Life Sciences, 1987
Synthesis and degradation of polyphosphoinositides in a rat brain synaptosome preparation were de... more Synthesis and degradation of polyphosphoinositides in a rat brain synaptosome preparation were depressed by phenobarbital. Phosphatidylinositol-4-phosphate kinase (PIP-kinase), the enzyme which synthesizes phosphatidylinositol-4,5-bisphosphate (PIP2) was most strongly affected (50% inhibition at 3 mM phenobarbital); phosphatidylinositol (PI-kinase) followed (50% at 15 mM). The phosphoesterases were less sensitive: PIP-monoesterase (50% at 39 mM), PIP2-monoesterase (at 47 mM), and, least inhibited, PIP-diesterase (50% at 65 mM) and PIP2-diesterase (at 68 mM). Phenobarbital by inhibiting PIP-kinase may reduce the membrane concentration of PIP2 and thus dampen the stimulus-response which leads to the hydrolysis of PIP2 and the formation of the second messenger, inositol-1,4,5-trisphosphate (IP3), involved in mobilization of intracellular Ca2+.
Life Sciences, 1984
Myelin basic protein and phosphatidylinositol-4-phosphate are phosphorylated in vitro by ATP and ... more Myelin basic protein and phosphatidylinositol-4-phosphate are phosphorylated in vitro by ATP and solubilized rat brain myelin. When both substrates are present together, the rate of phosphorylation of each is increased about eight-fold. It appears likely that the phosphate turnover of myelin basic protein and of phosphatidylinositol-4-phosphate are coupled in vivo.
Journal of Neuropathology and Experimental Neurology, 1983
Journal of Neurochemistry, 1993
To characterize the mechanism(s) for targeting of phospholipids lio peripheral nerve myelin, we e... more To characterize the mechanism(s) for targeting of phospholipids lio peripheral nerve myelin, we examined the kinetics of incosrporation of tritiated choke-, glycerol-, and ethanolamine-Labeled phospholipids into four subfractions: microsomes, mitochondria, myelin-like material, and purified myelin at I , 6, and 24 h after precursors were injected into sciatic nerves of 23-24-day-old rats. As validation of the fractionation scheme, a lag (> 1 h) in the accumulation of labeled phospholipids in the myelin-containing subfractions was found. This lag signifies the time between synthesis on organelles in Schwann cell cytoplasm and transport to myelin. In the present study, we find that sphingomyelin (choline-labeled) accumulated in myelin-rich subfractions only at 6 and 24 h, whereas phosphatidylserine (glycerol-labeled) and plasmalogen (ethanolamine-labeled) accumulated in the myelin-rich fractions by 1 h. The later phospho-lipids accumulate preferentially in the myelin-like fraction. These results are consistent with the notion that the targeting of sphingomyelin, a lipid present in the outer myelin leaflet, is different from the targeting of phosphatidylserine and ethanolamine plasmalogen, lipids in the inner leaflet. These findings are discussed in light of the possibility that sphingomyelin targeting is Golgi apparatus based, whereas phosphatidylserine and ethanolamine plasmalogen use a more direct transport system. Furthermore, the routes of phospholipid targeting mimic routes taken by myelin proteins Po (Golgi) and myelin basic proteins (more direct).
Journal of Biological Chemistry, 1971
Lipids, 1977
The hydrogen belts of membranes are defined as the regions consisting of hydrogen bond acceptors,... more The hydrogen belts of membranes are defined as the regions consisting of hydrogen bond acceptors, i.e., the C=O groups of glycero- and sphingolipids, and hydrogen bond donors, i.e., cholesterol-OH, sphingolipid-OH, proteins, and water. Lipid-lipid hydrogen bonding in these belts has been suggested. The connection of such hypothetical bonding with the condensation effect, i.e., the apparent reduction of surface area occupied by phospholipids in mixed monolayers with cholesterol, has been tested with lipids possissing and lacking C=O groups: diester, diether, and dialkyl phosphatidylcholine, and analogous polyoxyethylene diglycerides. Condensation by cholesterol was observed for all lipids. Consequently, the hypothetical lipid-C=O-cholesterol hydrogen bonding is not a prerequisite for the condensation effect.
Progress in brain research, 1973
Neurochemical Research, 1981
When unilamellar "stable" liposomes composed of a dialkyl analog of phosphatidy... more When unilamellar "stable" liposomes composed of a dialkyl analog of phosphatidylcholine, tetradecyloctadec-11-eno(1)phosphocholine (dialkyl-PC), plus cholesterol at 1:1 molar ratio, and a trace of [3H]dialkyl-PC were injected into the vitreous of the rabbit eye, macrophage infiltration and phagocytosis of lipid were observed in retina including the epiretinal myelinated nerve fiber bundles, with no other neurotoxic effects. Little or no incorporation of [3h]dialkyl-PC was observed in the distal tissues of the optic system. With "labile" vesicles composed of egg lecithin, trace amounts of [3H]dialkyl-PC, and phosphatidic acid, no morphological changes occurred. After a lag of more than 7 days [3H]dialkyl-PC appeared in superior colliculus, indicating axonal transport of the lipid in an anterograde direction. Experiments with submandibular and parotid gland indicated retrograde transport of the lipid. The data do not suggest axonal transport of intact (stable) liposomes, but suggest that intact phospholipid molecules can be axonally transported.
Neurochemical Research, 1980
We describe an attempt to incorporate a metabolically inert phospholipid analog into animal membr... more We describe an attempt to incorporate a metabolically inert phospholipid analog into animal membranes, especially myelin, in vivo, with the view of eventual long-term membrane modification or membrane engineering. A sonicated suspension of a mixture of [14C]phosphatidylcholine and its dialkyl analog, [3H] tetradecyloctadecano(1)phosphocholine, was injected into the brain of weanling rats. Samples were counted of whole brain, myelin, liver, and carcass, at intervals from 1 to 63 days, and the composition of the extracted lipid was determined by thin-layer chromatography. Both lipid labels were found to be cleared from the body at similar rates, but while phosphatidylcholine was metabolized within a day, with the label appearing mainly in the phosphatidylethanolamine fraction and in nonpolar lipids, the dialkylphosphatidylcholine remained intact, with retention in myelin of a small but almost constant amount for a month. Ways will have to be found to enhance uptake of the lipids by the brain.
Life Sciences, 1987
Synthesis and degradation of polyphosphoinositides in a rat brain synaptosome preparation were de... more Synthesis and degradation of polyphosphoinositides in a rat brain synaptosome preparation were depressed by phenobarbital. Phosphatidylinositol-4-phosphate kinase (PIP-kinase), the enzyme which synthesizes phosphatidylinositol-4,5-bisphosphate (PIP2) was most strongly affected (50% inhibition at 3 mM phenobarbital); phosphatidylinositol (PI-kinase) followed (50% at 15 mM). The phosphoesterases were less sensitive: PIP-monoesterase (50% at 39 mM), PIP2-monoesterase (at 47 mM), and, least inhibited, PIP-diesterase (50% at 65 mM) and PIP2-diesterase (at 68 mM). Phenobarbital by inhibiting PIP-kinase may reduce the membrane concentration of PIP2 and thus dampen the stimulus-response which leads to the hydrolysis of PIP2 and the formation of the second messenger, inositol-1,4,5-trisphosphate (IP3), involved in mobilization of intracellular Ca2+.
Life Sciences, 1984
Myelin basic protein and phosphatidylinositol-4-phosphate are phosphorylated in vitro by ATP and ... more Myelin basic protein and phosphatidylinositol-4-phosphate are phosphorylated in vitro by ATP and solubilized rat brain myelin. When both substrates are present together, the rate of phosphorylation of each is increased about eight-fold. It appears likely that the phosphate turnover of myelin basic protein and of phosphatidylinositol-4-phosphate are coupled in vivo.
Journal of Neuropathology and Experimental Neurology, 1983
Journal of Neurochemistry, 1993
To characterize the mechanism(s) for targeting of phospholipids lio peripheral nerve myelin, we e... more To characterize the mechanism(s) for targeting of phospholipids lio peripheral nerve myelin, we examined the kinetics of incosrporation of tritiated choke-, glycerol-, and ethanolamine-Labeled phospholipids into four subfractions: microsomes, mitochondria, myelin-like material, and purified myelin at I , 6, and 24 h after precursors were injected into sciatic nerves of 23-24-day-old rats. As validation of the fractionation scheme, a lag (> 1 h) in the accumulation of labeled phospholipids in the myelin-containing subfractions was found. This lag signifies the time between synthesis on organelles in Schwann cell cytoplasm and transport to myelin. In the present study, we find that sphingomyelin (choline-labeled) accumulated in myelin-rich subfractions only at 6 and 24 h, whereas phosphatidylserine (glycerol-labeled) and plasmalogen (ethanolamine-labeled) accumulated in the myelin-rich fractions by 1 h. The later phospho-lipids accumulate preferentially in the myelin-like fraction. These results are consistent with the notion that the targeting of sphingomyelin, a lipid present in the outer myelin leaflet, is different from the targeting of phosphatidylserine and ethanolamine plasmalogen, lipids in the inner leaflet. These findings are discussed in light of the possibility that sphingomyelin targeting is Golgi apparatus based, whereas phosphatidylserine and ethanolamine plasmalogen use a more direct transport system. Furthermore, the routes of phospholipid targeting mimic routes taken by myelin proteins Po (Golgi) and myelin basic proteins (more direct).
Journal of Biological Chemistry, 1971