Literature-based discovery of diabetes- and ROS-related targets

BackgroundReactive oxygen species (ROS) are known mediators of cellular damage in multiple diseases including diabetic complications. Despite its importance, no comprehensive database is currently available for the genes associated with ROS.MethodsWe present ROS- and diabetes-related targets (genes/proteins) collected from the biomedical literature through a text mining technology. A web-based literature mining tool, SciMiner, was applied to 1,154 biomedical papers indexed with diabetes and ROS by PubMed to identify relevant targets. Over-represented targets in the ROS-diabetes literature were obtained through comparisons against randomly selected literature. The expression levels of nine genes, selected from the top ranked ROS-diabetes set, were measured in the dorsal root ganglia (DRG) of diabetic and non-diabetic DBA/2J mice in order to evaluate the biological relevance of literature-derived targets in the pathogenesis of diabetic neuropathy.ResultsSciMiner identified 1,026 ROS- and diabetes-related targets from the 1,154 biomedical papers (http://jdrf.neurology.med.umich.edu/ROSDiabetes/). Fifty-three targets were significantly over-represented in the ROS-diabetes literature compared to randomly selected literature. These over-represented targets included well-known members of the oxidative stress response including catalase, the NADPH oxidase family, and the superoxide dismutase family of proteins. Eight of the nine selected genes exhibited significant differential expression between diabetic and non-diabetic mice. For six genes, the direction of expression change in diabetes paralleled enhanced oxidative stress in the DRG.ConclusionsLiterature mining compiled ROS-diabetes related targets from the biomedical literature and led us to evaluate the biological relevance of selected targets in the pathogenesis of diabetic neuropathy.

[1]  David S. Wishart,et al.  Nucleic Acids Research Polysearch: a Web-based Text Mining System for Extracting Relationships between Human Diseases, Genes, Mutations, Drugs Polysearch: a Web-based Text Mining System for Extracting Relationships between Human Diseases, Genes, Mutations, Drugs and Metabolites , 2008 .

[2]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[3]  Plamen Nikolov,et al.  Economic Costs of Diabetes in the U.S. in 2002 , 2003, Diabetes care.

[4]  A. Koller,et al.  PPARγ activation, by reducing oxidative stress, increases NO bioavailability in coronary arterioles of mice with Type 2 diabetes , 2004 .

[5]  F. DeRubertis,et al.  Acceleration of diabetic renal injury in the superoxide dismutase knockout mouse: effects of tempol. , 2007, Metabolism: clinical and experimental.

[6]  Adam D. Schuyler,et al.  SciMiner: web-based literature mining tool for target identification and functional enrichment analysis , 2009, Bioinform..

[7]  Dietrich Rebholz-Schuhmann,et al.  EBIMed - text crunching to gather facts for proteins from Medline , 2007, Bioinform..

[8]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[9]  E. Feldman,et al.  Sensory neurons and schwann cells respond to oxidative stress by increasing antioxidant defense mechanisms. , 2009, Antioxidants & redox signaling.

[10]  M. Fujimura,et al.  Exacerbation of delayed cell injury after transient global ischemia in mutant mice with CuZn superoxide dismutase deficiency. , 1999, Stroke.

[11]  E. Feldman,et al.  Mouse models of diabetic neuropathy , 2007, Neurobiology of Disease.

[12]  E. Feldman Oxidative stress and diabetic neuropathy: a new understanding of an old problem. , 2003, The Journal of clinical investigation.

[13]  R. Fisher On the Interpretation of χ2 from Contingency Tables, and the Calculation of P , 2010 .

[14]  S. Marklund,et al.  Enhanced diabetes-induced cataract in copper-zinc superoxide dismutase-null mice. , 2009, Investigative ophthalmology & visual science.

[15]  Ş. Çetinkalp,et al.  The effect of 1alpha,25(OH)2D3 vitamin over oxidative stress and biochemical parameters in rats where Type 1 diabetes is formed by streptozotocin. , 2009, Journal of diabetes and its complications.

[16]  C. Jenkinson,et al.  Proteomics Reveals Novel Oxidative and Glycolytic Mechanisms in Type 1 Diabetic Patients' Skin Which Are Normalized by Kidney-Pancreas Transplantation , 2010, PloS one.

[17]  E. Sarsour,et al.  Redox control of the cell cycle in health and disease. , 2009, Antioxidants & redox signaling.

[18]  James S. Wright,et al.  Targeted Deletion of the Cytosolic Cu/Zn-Superoxide Dismutase Gene (Sod1) Increases Susceptibility to Noise-Induced Hearing Loss , 1999, Audiology and Neurotology.

[19]  C. Collinet,et al.  Protein kinase C-α and -δ are required for NADPH oxidase activation in WKYMVm-stimulated IMR90 human fibroblasts , 2007 .

[20]  D. Cleveland,et al.  Non–cell autonomous toxicity in neurodegenerative disorders: ALS and beyond , 2009, The Journal of cell biology.

[21]  Yukita Sato,et al.  Oxidative stress and gene expression of antioxidant enzymes in the streptozotocin-induced diabetic rats under hyperbaric oxygen exposure. , 2009, International journal of clinical and experimental pathology.

[22]  Alfonso Valencia,et al.  Overview of BioCreAtIvE: critical assessment of information extraction for biology , 2005, BMC Bioinformatics.

[23]  C. Collinet,et al.  Protein kinase C-alpha and -delta are required for NADPH oxidase activation in WKYMVm-stimulated IMR90 human fibroblasts. , 2007, Archives of biochemistry and biophysics.

[24]  E. Feldman,et al.  Dyslipidemia-Induced Neuropathy in Mice : the Role of oxLDL / LOX-1 , 2009 .

[25]  A. Erol Insulin resistance is an evolutionarily conserved physiological mechanism at the cellular level for protection against increased oxidative stress. , 2007, BioEssays : news and reviews in molecular, cellular and developmental biology.

[26]  K. Talbot,et al.  Transgenics, toxicity and therapeutics in rodent models of mutant SOD1-mediated familial ALS , 2008, Progress in Neurobiology.

[27]  F. Hakim,et al.  Role of oxidative stress in diabetic kidney disease. , 2010, Medical science monitor : international medical journal of experimental and clinical research.

[28]  Jignesh M. Patel,et al.  Michigan molecular interactions r2: from interacting proteins to pathways , 2008, Nucleic Acids Res..

[29]  Jin-Shui Pan,et al.  Reactive oxygen species: A double-edged sword in oncogenesis , 2009 .

[30]  Ulf Leser,et al.  ALIBABA: PubMed as a graph , 2006, Bioinform..

[31]  G. V. Ommen,et al.  Medical genomics , 2001, European Journal of Human Genetics.

[32]  K. Kataoka,et al.  Potentiation by candesartan of protective effects of pioglitazone against type 2 diabetic cardiovascular and renal complications in obese mice , 2010, Journal of hypertension.

[33]  M. Gougerot-Pocidalo,et al.  Phosphorylation of p47phox sites by PKC alpha, beta II, delta, and zeta: effect on binding to p22phox and on NADPH oxidase activation. , 2002, Biochemistry.

[34]  M. Aslan,et al.  Activities of xanthine oxidoreductase and antioxidant enzymes in different tissues of diabetic rats. , 2003, The Journal of laboratory and clinical medicine.

[35]  E. Feldman,et al.  Oxidative stress in the pathogenesis of diabetic neuropathy. , 2004, Endocrine reviews.

[36]  Hiroyuki Ogata,et al.  KEGG: Kyoto Encyclopedia of Genes and Genomes , 1999, Nucleic Acids Res..

[37]  E. Feldman,et al.  Diabetic neuropathy: mechanisms to management. , 2008, Pharmacology & therapeutics.

[38]  E. Feldman,et al.  New Insights into the Mechanisms of Diabetic Neuropathy , 2004, Reviews in Endocrine and Metabolic Disorders.

[39]  A. Bokov,et al.  Is the oxidative stress theory of aging dead? , 2009, Biochimica et biophysica acta.

[40]  M. Brownlee Biochemistry and molecular cell biology of diabetic complications , 2001, Nature.

[41]  E. Schwedhelm,et al.  Clinical Pharmacokinetics of Antioxidants and Their Impact on Systemic Oxidative Stress , 2003, Clinical pharmacokinetics.

[42]  H. Ha,et al.  Reactive oxygen species-regulated signaling pathways in diabetic nephropathy. , 2003, Journal of the American Society of Nephrology : JASN.

[43]  R. Fisher On the Interpretation of χ2 from Contingency Tables, and the Calculation of P , 2018, Journal of the Royal Statistical Society Series A (Statistics in Society).

[44]  A. Koller,et al.  PPARgamma activation, by reducing oxidative stress, increases NO bioavailability in coronary arterioles of mice with Type 2 diabetes. , 2004, American journal of physiology. Heart and circulatory physiology.

[45]  J. Leahy Economic Costs of Diabetes in the U.S. in 2007 , 2008 .

[46]  Marina Vardanyan,et al.  Vascularization of the dorsal root ganglia and peripheral nerve of the mouse: Implications for chemical-induced peripheral sensory neuropathies , 2008, Molecular pain.

[47]  M. Khazaei,et al.  Moderate exercise attenuates caspase-3 activity, oxidative stress, and inhibits progression of diabetic renal disease in db/db mice. , 2009, American journal of physiology. Renal physiology.

[48]  K. Takagi,et al.  Increase in P-glycoprotein accompanied by activation of protein kinase Calpha and NF-kappaB p65 in the livers of rats with streptozotocin-induced diabetes. , 2008, Biochimica et biophysica acta.

[49]  E. Feldman,et al.  Oxidative injury and neuropathy in diabetes and impaired glucose tolerance , 2008, Neurobiology of Disease.

[50]  M. Beal,et al.  Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury , 1996, Nature Genetics.

[51]  O. Yasuda,et al.  Ezetimibe Ameliorates Cardiovascular Complications and Hepatic Steatosis in Obese and Type 2 Diabetic db/db Mice , 2010, Journal of Pharmacology and Experimental Therapeutics.

[52]  P. Shaw,et al.  Molecular and cellular pathways of neurodegeneration in motor neurone disease , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[53]  E. Feldman,et al.  Mechanisms of disease: The oxidative stress theory of diabetic neuropathy , 2008, Reviews in Endocrine and Metabolic Disorders.