Alterations in lipid metabolism gene expression and abnormal lipid accumulation in fibroblast explants from giant axonal neuropathy patients

Leung, Conrad L; Pang, Yinghua; Shu, Chang; Goryunov, Dmitry; Liem, Ronald KH
January 2007
BMC Genetics;2007, Vol. 8, p6
Academic Journal
Background: Giant axonal neuropathy (GAN) is a hereditary neurological disorder that affects both central and peripheral nerves. The main pathological hallmark of the disease is abnormal accumulations of intermediate filaments (IFs) in giant axons and other cell types. Mutations in the GAN gene, encoding gigaxonin, cause the disease. Gigaxonin is important in controlling protein degradation via the ubiquitin-proteasome system. The goal of this study was to examine global alterations in gene expression in fibroblasts derived from newly identified GAN families compared with normal cells. Results: We report the characterization of fibroblast explants obtained from two unrelated GAN patients. We identify three novel putative mutant GAN alleles and show aggregation of vimentin IFs in these fibroblasts. By microarray analysis, we also demonstrate that the expression of lipid metabolism genes of the GAN fibroblasts is disrupted, which may account for the abnormal accumulations of lipid droplets in these cells. Conclusion: Our findings suggest that aberrant lipid metabolism in GAN patients may contribute to the progression of the disease.


Related Articles

  • Identity-by-descent filtering as a tool for the identification of disease alleles in exome sequence data from distant relatives. Akula, Nirmala; Detera-Wadleigh, Sevilla; Yin Yao Shugart; Nalls, Michael; Steele, Jo; McMahon, Francis J. // BMC Proceedings;2011 Supplement 9, Vol. 5 Issue Suppl 9, p1 

    Large-scale, deep resequencing may be the next logical step in the genetic investigation of common complex diseases. Because each individual is likely to carry many thousands of variants, the identification of causal alleles requires an efficient strategy to reduce the number of candidate...

  • Comparative Analysis of Gene Regulation by the Transcription Factor PPARa between Mouse and Human. Rakhshandehroo, Maryam; Hooiveld, Guido; Müller, Michael; Kersten, Sander // PLoS ONE;2009, Vol. 4 Issue 8, p1 

    Background: Studies in mice have shown that PPARα is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPARα in human liver. Here we set out to compare the function of PPARα in mouse and human...

  • Association of polymorphic markers of the lipid metabolism genes with diabetic polyneuropathy in type 1 diabetes mellitus. Voron'ko, O. E.; Yakunina, N. Yu.; Strokov, I. A.; Lavrova, I. N.; Nosikov, V. V. // Molecular Biology;Mar2005, Vol. 39 Issue 2, p206 

    A possible association of the polymorphic markers e2/e3/e4 of the apolipoprotein E gene (APOE) andI /Dof the apolipoprotein B gene (APOB) with diabetic polyneuropathy (DPN) was analyzed in patients with type 1 diabetes mellitus (T1DM) with (N=86) or without (N=94) clinical signs of DPN. The two...

  • Expression of genes controlling fat deposition in two genetically diverse beef cattle breeds fed high or low silage diets. da Costa, Ana Sofia Henriques; Rico Pires, Virgínia Maria; Andrade Fontes, Carlos Mendes Godinho; Mestre Prates, José António // BMC Veterinary Research;2013, Vol. 9 Issue 1, p1 

    Background: Both genetic background and finishing system can alter fat deposition, thus indicating their influence on adipogenic and lipogenic factors. However, the molecular mechanisms underlying fat deposition and fatty acid composition in beef cattle are not fully understood. This study aimed...

  • Association of genes of lipid metabolism with measures of subclinical cardiovascular disease in the Diabetes Heart Study. Burdon, K. P.; Langefeld, C. D.; Beck, S. R.; Wagenknecht, L. E.; Carr, J. J.; Freedman, B. I.; Herrington, D.; Bowden, D. W. // Journal of Medical Genetics;Sep2005, Vol. 42 Issue 9, p720 

    Background: Dyslipidaemia is a well known risk factor far cardiovascular disease (CVD). Lipid metabolism is affected by a range of genes and proteins. This study investigated whether some of these genes are associated with measures of subclinical CVD. Methods: Polymorphisms of paraoxonase 1 and...

  • Eukaryotic expression, purification, identification, and tissue distribution of porcine PID1. Xiaoling CHEN; Huan WANG; Bo ZHOU; Zhiqing HUANG; Gang JIA; Guangmang LIU; Hua ZHAO // Turkish Journal of Biology;2015, Vol. 39 Issue 5, p705 

    Phosphotyrosine interaction domain containing 1 (PID1) is a recently discovered gene related to lipid metabolism and may play an important role in fat deposition. In this study, in order to scale up the production of the active recombinant porcine PID1 (pPID1) protein, we reported the expression...

  • A plasma-membrane E-MAP reveals links of the eisosome with sphingolipid metabolism and endosomal trafficking. Aguilar, Pablo S.; Fröhlich, Florian; Rehman, Michael; Shales, Mike; Ulitsky, Igor; Olivera-Couto, Agustina; Braberg, Hannes; Shamir, Ron; Walter, Peter; Mann, Matthias; Ejsing, Christer S.; Krogan, Nevan J.; Walther, Tobias C. // Nature Structural & Molecular Biology;Jul2010, Vol. 17 Issue 7, p901 

    The plasma membrane delimits the cell and controls material and information exchange between itself and the environment. How different plasma-membrane processes are coordinated and how the relative abundance of plasma-membrane lipids and proteins is homeostatically maintained are not yet...

  • Gene Expression Profiling of Soft and Firm Atlantic Salmon Fillet. Larsson, Thomas; Mørkøre, Turid; Kolstad, Kari; Østbye, Tone-Kari; Afanasyev, Sergey; Krasnov, Aleksei // PLoS ONE;Jun2012, Vol. 7 Issue 6, p1 

    Texture of salmon fillets is an important quality trait for consumer acceptance as well as for the suitability for processing. In the present work we measured fillet firmness in a population of farmed Atlantic salmon with known pedigree and investigated the relationship between this trait and...

  • Role of AMP-activated protein kinase in the coordinated expression of genes controlling glucose and lipid metabolism in mouse white skeletal muscle. Long, Y. C.; Barnes, B. R.; Mahlapuu, M.; Steiler, T. L.; Martinsson, S.; Leng, Y.; Wallberg-Henriksson, H.; Andersson, L.; Zierath, J. R. // Diabetologia;Nov2005, Vol. 48 Issue 11, p2354 

    Aims/hypothesis: AMP-activated protein kinase (AMPK) regulates metabolic adaptations in skeletal muscle. The aim of this study was to investigate whether AMPK modulates the expression of skeletal muscle genes that have been implicated in lipid and glucose metabolism under fed or fasting...


Other Topics