Substrate reduction reduces gangliosides in postnatal cerebrum-brainstem and cerebellum in GM1 gangliosidosis mice

Kasperzyk, Julie L.; d’Azzo, Alessandra; Platt, Frances M.; Alroy, Joseph; Seyfried, Thomas N.

doi:10.1194/jlr.m400411-jlr200

Cited by 67 publications

(79 citation statements)

References 59 publications

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“…Neutral lipid, acidic lipid and ganglioside HPTLC plates were developed and visualized as we previously described. 21 …”

Section: High-performance Thin-layer Chromatographymentioning

confidence: 99%

“…21,22 The amount of neutral lipids and acidic lipids spotted on the HPTLC for each cell line was equivalent to approximately 70 lg and 400 lg of cell dry weight, respectively. An internal standard (oleyl alcohol) was added to the neutral lipid and acidic lipid samples to control for the amount of lipids spotted.…”

Section: High-performance Thin-layer Chromatographymentioning

confidence: 99%

“…21,22 Ganglioside sialic acid was quantified by the gas-liquid chromatographic method of Yu and Ledeen. 23 …”

Section: Lipid Isolation Purification and Quantificationmentioning

confidence: 99%

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Metastatic cancer cells with macrophage properties: Evidence from a new murine tumor model

Huysentruyt

Mukherjee

Banerjee

et al. 2008

Intl Journal of Cancer

154

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Metastasis is the process by which cancer cells disseminate from the primary neoplasm and invade surrounding tissue and distant organs, and is the primary cause of morbidity and mortality for cancer patients. Most conventional cancer therapies are ineffective in managing tumor metastasis. This has been due in large part to the absence of in vivo metastatic models that represent the full spectrum of metastatic disease. Here we identify 3 new spontaneously arising tumors in the inbred VM mouse strain, which has a relatively high incidence of CNS tumors. Two of the tumors (VM-M2 and VM-M3) reliably expressed all of the major biological processes of metastasis to include local invasion, intravasation, immune system survival, extravasation and secondary tumor formation involving liver, kidney, spleen, lung and brain. Metastasis was assessed through visual organ inspection, histology, immunohistochemistry and bioluminescence imaging. The metastatic VM tumor cells also expressed multiple properties of macrophages including morphological appearance, surface adhesion, phagocytosis, total lipid composition (glycosphingolipids and phospholipids) and gene expression (CD11b, Iba1, F4/80, CD68, CD45 and CXCR4). The third tumor (VM-NM1) grew rapidly and expressed properties of neural stem/progenitor cells, but was neither invasive nor metastatic. Our data indicate that spontaneous brain tumors can arise from different cell types in VM mice and that metastatic cancer can represent a disease of macrophage-like cells similar to those described in several human metastatic cancers.The new VM tumor model will be useful for defining the biological processes of cancer metastasis and for evaluating potential therapies for tumor management. ' 2008 Wiley-Liss, Inc.Key words: metastasis; microglia; gangliosides; neural stem cell; glioblastoma Metastasis is the process by which cancer cells disseminate from the primary neoplasm and invade surrounding tissue and distant organs and is the primary cause of morbidity and mortality for cancer patients. This process involves cancer cell detachment from the primary tumor, intravasation into the circulation, evasion of immune attack, extravasation at distant capillary beds and invasion and proliferation in distant organs. [1][2][3] In addition, the metastatic cells establish a microenvironment facilitating colonization (angiogenesis and further proliferation), resulting in macroscopic malignant secondary tumors.1-4 Metastatic cells preferentially invade those organs (lymph nodes, lung, liver, brain, bone, pleura and peritoneum) that promote tumor cell growth and survival consistent with the ''seed and soil'' hypothesis. 1,5,6 The metastatic and invasive potential of cancer cells is often correlated with abnormalities in phospholipids and in cell-surface glycolipids, which contribute to tumor progression.7-10 Hence, aberrant cellular migration and proliferation characterize the metastatic phenomenon.In this study, we analyzed the morphological, behavioral, biochemical and genetic properties of 3 n...

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“…Neutral lipid, acidic lipid and ganglioside HPTLC plates were developed and visualized as we previously described. 21 …”

Section: High-performance Thin-layer Chromatographymentioning

confidence: 99%

Section: High-performance Thin-layer Chromatographymentioning

confidence: 99%

See 1 more Smart Citation

Metastatic cancer cells with macrophage properties: Evidence from a new murine tumor model

Huysentruyt

Mukherjee

Banerjee

et al. 2008

Intl Journal of Cancer

154

View full text Add to dashboard Cite

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“…Total lipids were isolated and purified from lyophilized brain tissue by using modifications of previously described procedures (Seyfried et al, 1978a, Seyfried et al, 1978b, Hauser et al, 2004, Kasperzyk et al, 2005, Denny et al, 2006. Neutral and acidic lipids were separated by using DEAE-Sephadex (A-25; Pharmacia Biotech, Upsala, Sweden) column chromatography as previously described (Macala et al, 1983, Kasperzyk et al, 2005.…”

Section: Lipid Isolation Purification and Quantificationmentioning

confidence: 99%

“…Neutral and acidic lipids were separated by using DEAE-Sephadex (A-25; Pharmacia Biotech, Upsala, Sweden) column chromatography as previously described (Macala et al, 1983, Kasperzyk et al, 2005. The total lipid extract, suspended in solvent A (CHCl 3 :CH 3 OH:H 2 O, 30:60:8 by vol), was then applied to a DEAE-Sephadex column (1.2 ml bed volume) that had been equilibrated with solvent A.…”

Section: Lipid Isolation Purification and Quantificationmentioning

confidence: 99%

Glycolipid and ganglioside metabolism imbalances in Huntington's disease

Desplats

Denny

Kass

et al. 2007

Neurobiology of Disease

122

120

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We have explored genome-wide expression of genes related to glycobiology in exon 1 transgenic Huntington's disease (HD) mice using a custom designed GLYCOv2 chip and Affymetrix microarray analyses. We validated, using quantitative real-time PCR, abnormal expression levels of genes encoding glycosyltransferases in the striatum of R6/1 transgenic mice, as well as in postmortem caudate from human HD patients. Many of these genes show differential regional expression within the CNS, as indicated by in situ hybridization analysis, suggesting region-specific regulation of this system in the brain. We further show disrupted patterns of glycolipids (acidic and neutral lipids) and/ or ganglioside levels in both the forebrain of the R6/1 transgenic mice and caudate samples from human HD subjects. These findings reveal novel disruptions in glycolipid/ganglioside metabolic pathways in the pathology of HD and suggest that the development of new targets to restore glycosphingolipid balance may act to ameliorate some symptoms in HD.

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Influence of caloric restriction on motor behavior, longevity, and brain lipid composition in Sandhoff disease mice

Denny

Kasperzyk

Gorham

et al. 2006

J of Neuroscience Research

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Caloric restriction (CR), which improves health and increases longevity, was studied as a therapy in a hexosaminidase beta knockout mouse model of Sandhoff disease (SD), an incurable neurodegenerative disease involving accumulation of brain ganglioside GM2 and asialo-GM2 (GA2). Adult mice were fed a rodent chow diet either ad libitum (AL) or restricted to reduce body weight by 15-18% (CR). Although GM2 and GA2 were elevated, no significant differences were seen between the Hexb-/- and the Hexb+/- mice for most brain phospholipids and cholesterol. Cerebrosides and sulfatides were reduced in the Hexb-/- mice. In addition, rotorod performance was significantly worse in the Hexb-/- mice than in the Hexb+/- mice. CR, which decreased circulating glucose and elevated ketone bodies, significantly improved rotorod performance and extended longevity in the Hexb-/- mice but had no significant effect on brain lipid composition or on cytoplasmic neuronal vacuoles. The expression of CD68 and F4/80 was significantly less in the CR-fed than in the AL-fed Hexb-/- mice. We suggest that the CR delays disease progression in SD and possibly in other ganglioside storage diseases through anti-inflammatory mechanisms.

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Substrate reduction reduces gangliosides in postnatal cerebrum-brainstem and cerebellum in GM1 gangliosidosis mice

Cited by 67 publications

References 59 publications

Metastatic cancer cells with macrophage properties: Evidence from a new murine tumor model

Metastatic cancer cells with macrophage properties: Evidence from a new murine tumor model

Glycolipid and ganglioside metabolism imbalances in Huntington's disease

Influence of caloric restriction on motor behavior, longevity, and brain lipid composition in Sandhoff disease mice

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