Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
November-2018 Volume 18 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
November-2018 Volume 18 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Silencing of pantothenate kinase 2 reduces endothelial cell angiogenesis

  • Authors:
    • Francesca Pagani
    • Akansha Trivedi
    • Deepak Khatri
    • Daniela Zizioli
    • Emirena Garrafa
    • Stefania Mitola
    • Dario Finazzi
  • View Affiliations / Copyright

    Affiliations: Section of Biotechnology, Department of Molecular and Translational Medicine, University of Brescia, I‑25123 Brescia, Italy
  • Pages: 4739-4746
    |
    Published online on: September 13, 2018
       https://doi.org/10.3892/mmr.2018.9480
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Coenzyme A (CoA) is an essential cofactor of cellular metabolism that is involved in ~4% of cellular reactions. Its de novo production relies on five subsequent enzymatic steps, starting with the phosphorylation of vitamin B5. Pantothenate kinase 2 (PANK2) and coenzyme A synthase (COASY) catalyze the first and last steps of this pathway. Mutations in these genes lead to severe and progressive movement disorders, with neurodegeneration and iron accumulation in the basal ganglia, known as PANK2‑ and COASY protein‑associated neurodegeneration, respectively. Given the ubiquitous role of CoA in cellular metabolism, it is still not clear why patients carrying PANK2 and COASY mutations develop almost exclusively neurological symptoms. Important clues are the energetic profile of neural cells as well as the high levels of PANK2 expression in the brain; however, other features may contribute to this selective tissue vulnerability. Notably, when pank2 or coasy expression was suppressed in zebrafish evident perturbation of neuronal development was observed, as well as severe defects in vasculature formation. Supplementation of CoA to fish water prevented the appearance of the phenotype, thereby confirming the specific connection with the availability of the metabolic cofactor. The present study investigated the associations between PANK2 defects and angiogenesis in a mammalian setting, and revealed that PANK2 expression was required for normal angiogenetic properties of human umbilical vein endothelial cells.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Zhou B, Westaway SK, Levinson B, Johnson MA, Gitschier J and Hayflick SJ: A novel pantothenate kinase gene (pank2) is defective in hallervorden-spatz syndrome. Nat Genet. 28:345–349. 2001. View Article : Google Scholar : PubMed/NCBI

2 

Angelini L, Nardocci N, Rumi V, Zorzi C, Strada L and Savoiardo M: Nhallervorden-spatz disease: Clinical and mri study of 11 cases diagnosed in life. J Neurol. 239:417–425. 1992. View Article : Google Scholar : PubMed/NCBI

3 

Swaiman KF: Hallervorden-Spatz syndrome and brain iron metabolism. Arch Neurol. 48:1285–1293. 1991. View Article : Google Scholar : PubMed/NCBI

4 

Hayflick SJ, Westaway SK, Levinson B, Zhou B, Johnson MA, Ching KH and Gitschier J: Genetic, clinical, and radiographic delineation of hallervorden-Spatz syndrome. N Engl J Med. 348:33–40. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Hayflick SJ, Hartman M, Coryell J, Gitschier J and Rowley H: Brain MRI in neurodegeneration with brain iron accumulation with and without PANK2 mutations. Ajnr Am J Neuroradiol. 27:1230–1233. 2006.PubMed/NCBI

6 

Abiko Y: Investigations on pantothenic acid and its related compounds. IX. Biochemical studies.4. Separation and substrate specificity of pantothenate kinase and phosphopantothenoylcysteine synthetase. J Biochem. 61:290–299. 1967. View Article : Google Scholar : PubMed/NCBI

7 

Dansie LE, Reeves S, Miller K, Zano SP, Frank M, Pate C, Wang J and Jackowski S: Physiological roles of the pantothenate kinases. Biochem Soc Trans. 42:1033–1036. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Hörtnagel K, Prokisch H and Meitinger T: An isoform of hPANK2, deficient in pantothenate kinase-associated neurodegeneration, localizes to mitochondria. Hum Mol Genet. 12:321–327. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Brunetti D, Dusi S, Morbin M, Uggetti A, Moda F, D'Amato I, Giordano C, d'Amati G, Cozzi A, Levi S, et al: Pantothenate kinase-associated neurodegeneration: Altered mitochondria membrane potential and defective respiration in Pank2 knock-out mouse model. Hum Mol Genet. 21:5294–5305. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Alfonso-Pecchio A, Garcia M, Leonardi R and Jackowski S: Compartmentalization of mammalian pantothenate kinases. PLoS One. 7:e495092012. View Article : Google Scholar : PubMed/NCBI

11 

Kotzbauer PT, Truax AC, Trojanowski JQ and Lee VM: Altered neuronal mitochondrial coenzyme A synthesis in neurodegeneration with brain iron accumulation caused by abnormal processing, stability, and catalytic activity of mutant pantothenate kinase 2. J Neurosci. 25:689–698. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Leonardi R, Zhang YM, Lykidis A, Rock CO and Jackowski S: Localization and regulation of mouse pantothenate kinase 2. FEBS Lett. 581:4639–4644. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Leonardi R, Rock CO, Jackowski S and Zhang YM: Activation of human mitochondrial pantothenate kinase 2 by palmitoylcarnitine. Proc Natl Acad Sci USA. 104:1494–1499. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Levi S and Finazzi D: Neurodegeneration with brain iron accumulation: Update on pathogenic mechanisms. Front Pharmacol. 5:992014. View Article : Google Scholar : PubMed/NCBI

15 

Aoun M and Tiranti V: Mitochondria: A crossroads for lipid metabolism defect in neurodegeneration with brain iron accumulation diseases. Int J Biochem Cell Biol. 63:25–31. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Zizioli D, Tiso N, Guglielmi A, Saraceno C, Busolin G, Giuliani R, Khatri D, Monti E, Borsani G, Argenton F and Finazzi D: KNock-down of pantothenate kinase 2 severely affects the development of the nervous and vascular system in zebrafish, providing new insights into PKAN disease. Neurobiol Dis. 85:35–48. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Rana A, Seinen E, Siudeja K, Muntendam R, Srinivasan B, van der Want JJ, Hayflick S, Reijngoud DJ, Kayser O and Sibon OC: Pantethine rescues a Drosophila model for pantothenate kinase-associated neurodegeneration. Proc Natl Acad Sci USA. 107:6988–6993. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Srinivasan B, Baratashvili M, van der Zwaag M, Kanon B, Colombelli C, Lambrechts RA, Schaap O, Nollen EA, Podgoršek A, Kosec G, et al: Extracellular 4′-phosphopantetheine is a source for intracellular coenzyme A synthesis. Nat Chem Biol. 11:784–792. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Di Meo I, Colombelli C, Srinivasan B, de Villiers M, Hamada J, Jeong SY, Fox R, Woltjer RL, Tepper PG, Lahaye LL, et al: Acetyl-4′-phosphopantetheine is stable in serum and prevents phenotypes induced by pantothenate kinase deficiency. Sci Rep. 7:112602017. View Article : Google Scholar : PubMed/NCBI

20 

Khatri D, Zizioli D, Tiso N, Facchinello N, Vezzoli S, Gianoncelli A, Memo M, Monti E, Borsani G and Finazzi D: Down-regulation of coasy, the gene associated with NBIA-VI, reduces Bmp signaling, perturbs dorso-ventral patterning and alters neuronal development in zebrafish. Sci Rep. 6:376602016. View Article : Google Scholar : PubMed/NCBI

21 

Dusi S, Valletta L, Haack TB, Tsuchiya Y, Venco P, Pasqualato S, Goffrini P, Tigano M, Demchenko N, Wieland T, et al: Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation. Am J Hum Genet. 94:11–22. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Annesi G, Gagliardi M, Iannello G and Quattrone A, Iannello G and Quattrone A: Mutational analysis of COASY in an italian patient with NBIA. Parkinsonism Relat Disord. 28:150–151. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Grillo E, Ravelli C, Corsini M, Ballmer-Hofer K, Zammataro L, Oreste P, Zoppetti G, Tobia C, Ronca R, Presta M and Mitola S: Monomeric gremlin is a novel vascular endothelial growth factor receptor-2 antagonist. Oncotarget. 7:35353–35368. 2016. View Article : Google Scholar : PubMed/NCBI

24 

Gatta LB, Vitali M, Verardi R, Arosio P and Finazzi D: Inhibition of heme synthesis alters amyloid precursor protein processing. J Neural Transm (Vienna). 116:79–88. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative pcr and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Poli M, Derosas M, Luscieti S, Cavadini P, Campanella A, Verardi R, Finazzi D and Arosio P: Pantothenate kinase-2 (Pank2) silencing causes cell growth reduction, cell-specific ferroportin upregulation and iron deregulation. Neurobiol Dis. 39:204–210. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Siudeja K, Srinivasan B, Xu L, Rana A, de Jong J, Nollen EA, Jackowski S, Sanford L, Hayflick S and Sibon OC: Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration. Embo Mol Med. 3:755–766. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Campanella A, Privitera D, Guaraldo M, Rovelli E, Barzaghi C, Garavaglia B, Santambrogio P, Cozzi A and Levi S: Skin fibroblasts from pantothenate kinase-associated neurodegeneration patients show altered cellular oxidative status and have defective iron-handling properties. Hum Mol Genet. 21:4049–4059. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Vanetti C, Bifari F, Vicentini LM and Cattaneo MG: Fatty acids rather than hormones restore in vitro angiogenesis in human male and female endothelial cells cultured in charcoal-stripped serum. PLoS One. 12:e01895282017. View Article : Google Scholar : PubMed/NCBI

30 

Schoors S, Bruning U, Missiaen R, Queiroz KC, Borgers G, Elia I, Zecchin A, Cantelmo AR, Christen S, Goveia J, et al: Fatty acid carbon is essential for dNTP synthesis in endothelial cells. Nature. 520:192–197. 2015. View Article : Google Scholar : PubMed/NCBI

31 

Wong BW, Wang X, Zecchin A, Thienpont B, Cornelissen I, Kalucka J, García-Caballero M, Missiaen R, Huang H, Brüning U, et al: The role of fatty acid β-oxidation in lymphangiogenesis. Nature. 542:49–54. 2017. View Article : Google Scholar : PubMed/NCBI

32 

Brown WR and Thore CR: Review: Cerebral microvascular pathology in ageing and neurodegeneration. Neuropathol Appl Neurobiol. 37:56–74. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Carmeliet P and Ruiz de Almodovar C: VEGF ligands and receptors: Implications in neurodevelopment and neurodegeneration. Cell Mol Life Sci. 70:1763–1778. 2013. View Article : Google Scholar : PubMed/NCBI

34 

Woltjer RL, Reese LC, Richardson BE, Tran H, Green S, Pham T, Chalupsky M, Gabriel I, Light T, Sanford L, et al: Pallidal neuronal apolipoprotein E in pantothenate kinase-associated neurodegeneration recapitulates ischemic injury to the globus pallidus. Mol Genet Metab. 116:289–297. 2015. View Article : Google Scholar : PubMed/NCBI

35 

Wolfram-Gabel R and Maillot C: Vascular networks of the nucleus lentiformis. Surg Radiol Anat. 16:373–377. 1994. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Pagani F, Trivedi A, Khatri D, Zizioli D, Garrafa E, Mitola S and Finazzi D: Silencing of pantothenate kinase 2 reduces endothelial cell angiogenesis. Mol Med Rep 18: 4739-4746, 2018.
APA
Pagani, F., Trivedi, A., Khatri, D., Zizioli, D., Garrafa, E., Mitola, S., & Finazzi, D. (2018). Silencing of pantothenate kinase 2 reduces endothelial cell angiogenesis. Molecular Medicine Reports, 18, 4739-4746. https://doi.org/10.3892/mmr.2018.9480
MLA
Pagani, F., Trivedi, A., Khatri, D., Zizioli, D., Garrafa, E., Mitola, S., Finazzi, D."Silencing of pantothenate kinase 2 reduces endothelial cell angiogenesis". Molecular Medicine Reports 18.5 (2018): 4739-4746.
Chicago
Pagani, F., Trivedi, A., Khatri, D., Zizioli, D., Garrafa, E., Mitola, S., Finazzi, D."Silencing of pantothenate kinase 2 reduces endothelial cell angiogenesis". Molecular Medicine Reports 18, no. 5 (2018): 4739-4746. https://doi.org/10.3892/mmr.2018.9480
Copy and paste a formatted citation
x
Spandidos Publications style
Pagani F, Trivedi A, Khatri D, Zizioli D, Garrafa E, Mitola S and Finazzi D: Silencing of pantothenate kinase 2 reduces endothelial cell angiogenesis. Mol Med Rep 18: 4739-4746, 2018.
APA
Pagani, F., Trivedi, A., Khatri, D., Zizioli, D., Garrafa, E., Mitola, S., & Finazzi, D. (2018). Silencing of pantothenate kinase 2 reduces endothelial cell angiogenesis. Molecular Medicine Reports, 18, 4739-4746. https://doi.org/10.3892/mmr.2018.9480
MLA
Pagani, F., Trivedi, A., Khatri, D., Zizioli, D., Garrafa, E., Mitola, S., Finazzi, D."Silencing of pantothenate kinase 2 reduces endothelial cell angiogenesis". Molecular Medicine Reports 18.5 (2018): 4739-4746.
Chicago
Pagani, F., Trivedi, A., Khatri, D., Zizioli, D., Garrafa, E., Mitola, S., Finazzi, D."Silencing of pantothenate kinase 2 reduces endothelial cell angiogenesis". Molecular Medicine Reports 18, no. 5 (2018): 4739-4746. https://doi.org/10.3892/mmr.2018.9480
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team