Biochemical Analysis of Myelin Lipids and Proteins in a Model of Methyl Donor Pathway Deficit: Effect of S-Adenosylmethionine

Bianchi, Roberto; Calzi, F.; Savaresi, Sara; Sciarretta-Birolo, Roberto; Tsankova, Virginia; Tacconi, M.T.

doi:10.1006/exnr.1999.7132

Cited by 12 publications

(8 citation statements)

References 54 publications

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“…Furthermore, PINCH may form covalent associations like prosaposin and gangliosides (Misasi et al, 1998) or in fact dimerize in the Western assay as a result of boiling. Multimeriza-tion of proteolipid protein and myelin basic protein in denaturing conditions has been observed previously (Golds and Braun, 1978;Bianchi et al, 1999). Furthermore, the larger 70 kDa PINCH protein was also identified by a mouse antihistidine antibody (Fig.…”

Section: Resultssupporting

confidence: 80%

Identification of PINCH in Schwann cells and DRG neurons: Shuttling and signaling after nerve injury

Campana

Myers

Rearden

2003

Glia

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Particularly interesting new cysteine-histidine rich protein (PINCH) is a double zinc finger domain (LIM)-only adapter protein that functions to recruit the integrin-linked kinase (ILK) to sites of integrin activation. Genetic studies have shown that PINCH and ILK are required for integrin signaling. Since integrin activation is associated with Schwann cell migration, neurite outgrowth and regeneration, this study examined PINCH in the normal peripheral nervous system and after chronic constriction injury (CCI) in adult Sprague-Dawley rats. Immunohistochemistry identified PINCH immunoreactivity in cell bodies of dorsal root ganglia (DRG) neurons, axons, satellite cells, and Schwann cells. PINCH immunostaining was localized to the membrane of uninjured DRG cell bodies consistent with its localization at a site of integrin activation. In contrast, 5 days following CCI, PINCH immunostaining was diffuse throughout the DRG cell cytoplasm. Confocal microscopy of primary and transformed Schwann cells localized PINCH in cytoplasmic, perinuclear and nuclear areas. Examination of the PINCH sequence revealed a putative leucine-rich nuclear export signal (NES) and an overlapping basic nuclear localization signal (NLS). To demonstrate nuclear export of PINCH, rabbit anti-PINCH IgG was microinjected into Schwann cell nuclei and allowed to combine with PINCH contained within the nucleus. Immunofluorescence showed that the PINCH and anti-PINCH IgG complex rapidly translocated to the cytoplasm. Treatment with leptomycin B caused nuclear accumulation of PINCH, indicating that the CRM1 pathway mediates nuclear export of PINCH. ILK activity in Schwann cells was enhanced by platelet-derived growth factor (PDGF) and tumor necrosis factor alpha. PINCH immunoprecipitates from PDGF- and TNFalpha-stimulated Schwann cells contained several high-molecular-weight threonine-phosphorylated proteins. Taken together, these results indicate that PINCH is an abundant shuttling/signaling protein in Schwann cells and DRG neurons.

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Section: Resultssupporting

confidence: 80%

Identification of PINCH in Schwann cells and DRG neurons: Shuttling and signaling after nerve injury

Campana

Myers

Rearden

2003

Glia

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“…In animal models, drug-induced SAM deficiency is associated with vacuolar demyelination of the spinal cord histologically similar to the SCD found in human patients, [24][25][26] and depressed CSF SAM levels have been reported in patients with myelopathy associated with impaired methyl transfer metabolism. In animal models, drug-induced SAM deficiency is associated with vacuolar demyelination of the spinal cord histologically similar to the SCD found in human patients, [24][25][26] and depressed CSF SAM levels have been reported in patients with myelopathy associated with impaired methyl transfer metabolism.…”

Section: Clinical Evidence Of Progressive Myelopathy Based Onsupporting

confidence: 53%

“…4,5 Histopathologically, AM is characterized by vacuoles in white matter, predominantly in the lateral and posterior columns of the thoracic spinal cord, with sparse macrophage infiltration. [7][8][9][10][11] Impairment of the methylation pathway in SCD, other toxic and metabolic diseases, or experimental animal models leads to spinal cord vacuolization indistinguishable from that observed in AIDS. 2,4,5 The histopathology of AM bears a striking resemblance to the metabolic myelopathy of subacute combined degeneration (SCD) related to cobalamin (vitamin B 12 ) deficiency.…”

mentioning

confidence: 99%

Abnormal cobalamin-dependent transmethylation in AIDS-associated myelopathy

Rocco

Bottiglieri²,

Werner³

et al. 2002

Neurology

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“…In our studies of rat brain, we were unable to detect any 13 C labeling on PtdC in either whole brain experiments (12) or in the current investigation involving specific brain areas. Furthermore, the literature suggests that the activity of PEMT is extremely low in adult brain tissue thus making any contributions from the pathway negligible (28)(29)(30). We have also conducted NMR studies in neonate rat brains following administration of 13 C-labeled ethanolamine, which also failed to show any appreciable synthesis of PtdC via the PEMT pathway (unpublished data).…”

Section: Phospholipid Profilementioning

confidence: 88%

Administration of Myo-inositol Plus Ethanolamine Elevates Phosphatidylethanolamine Plasmalogen in the Rat Cerebellum

Hoffman-Kuczynski

Reo

2005

Neurochem Res

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Plasmalogens are ether-linked phospholipids highly abundant in nervous tissue. Previously we demonstrated that acute administration of myo-inositol (myo-Ins) + [2-(13)C] ethanolamine ([2-(13)C]Etn) significantly elevated phosphatidylethanolamine plasmalogen (PlsEtn) in rat whole brain. Current experiments investigated the effects of acute myo-Ins+[2-(13)C]Etn administration on [PlsEtn] and the biosynthesis of new Etn lipids using NMR spectroscopy in rat cerebral cortex, hippocampus, brainstem, midbrain and cerebellum. Treated rats received a single dose of myo-Ins + [2-(13)C]Etn and controls received saline rather than myoIns. Data reveal that the cerebellum is the brain region most affected by treatment, which resulted in a 22% increase in [PlsEtn] and 89% increase in newly synthesized Etn lipids relative to controls (P < 0.05). Furthermore, the cerebellar PlsEtn/phosphatidylethanolamine ratio and molar percentage of PlsEtn were significantly elevated by 12% and 8%, respectively (P < 0.05). These data suggest that myo-Ins influences Etn lipid metabolism in brain, particularly in the cerebellum where there is a stimulation in the biosynthesis of new Etn lipids with a preference towards PlsEtn.

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Biochemical Analysis of Myelin Lipids and Proteins in a Model of Methyl Donor Pathway Deficit: Effect of S-Adenosylmethionine

Cited by 12 publications

References 54 publications

Identification of PINCH in Schwann cells and DRG neurons: Shuttling and signaling after nerve injury

Identification of PINCH in Schwann cells and DRG neurons: Shuttling and signaling after nerve injury

Abnormal cobalamin-dependent transmethylation in AIDS-associated myelopathy

Administration of Myo-inositol Plus Ethanolamine Elevates Phosphatidylethanolamine Plasmalogen in the Rat Cerebellum

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