Advertisement

Roles for AMP-Activated Protein Kinase in RPE Cell Function

  • Suofu QinEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)

Abstract

AMP-activated protein kinase (AMPK) is a heterotrimer, comprising a catalytic α subunit and regulatory β and γ subunits, that senses cellular energy levels. When energy supply is compromised, activated AMPK limits energy utilization and promotes energy production to ensue cell survival. Intriguingly, recent findings show that AMPK is important in functions that go beyond the maintenance of energy homeostasis. In this mini-review, the role of AMPK in controlling retinal pigment epithelium cell phagocytosis, permeability, immune response, and survival under oxidative stress is discussed.

Keywords

AMPK Barrier function Inflammation Phagocytosis RPE Survival 

References

  1. Amin N, Khan A, St Johnston D et al (2009) LKB1 regulates polarity remodeling and adherens junction formation in the Drosophila eye. Proc Natl Acad Sci USA 106:8941–8946PubMedCrossRefGoogle Scholar
  2. Carling D (2004) The AMP-activated protein kinase cascade--a unifying system for energy control. Trends Biochem Sci 29:18–24PubMedCrossRefGoogle Scholar
  3. da Silva Xavier G, Leclerc I, Salt IP et al (2000) Role of AMP-activated protein kinase in the regulation by glucose of islet b cell gene expression. Proc Natl Acad Sci USA 97:4023–4028Google Scholar
  4. Fogarty S, Hardie DG (2010) Development of protein kinase activators: AMPK as a target in metabolic disorders and cancer. Biochim Biophys Acta 1804:581–591PubMedGoogle Scholar
  5. Giri S, Nath N, Smith B et al (2004) 5-aminoimidazole-4-carboxamide-1-b-4-ribofuranoside inhibits proinflammatory response in glial cells: a possible role of AMP-activated protein kinase. J Neurosci 24:479–487PubMedCrossRefGoogle Scholar
  6. Hageman GS, Luthert PJ, Victor Chong NH et al (2001) An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch’s membrane interface in aging and age-related macular degeneration. Prog Retin Eye Res 20:705–732PubMedCrossRefGoogle Scholar
  7. Lee JH, Koh H, Kim M et al (2007) Energy-dependent regulation of cell structure by AMP-activated protein kinase. Nature 447:1017–1020PubMedCrossRefGoogle Scholar
  8. Liu C, Liang B, Wang Q et al (2010) Activation of AMP-activated protein kinase a1 alleviates endothelial cell apoptosis by increasing the expression of anti-apoptotic proteins Bcl-2 and survivin. J Biol Chem 285:15346–15355PubMedCrossRefGoogle Scholar
  9. Mirouse V, Swick LL, Kazgan N et al (2007) LKB1 and AMPK maintain epithelial cell polarity under energetic stress. J Cell Biol 177:387–392PubMedCrossRefGoogle Scholar
  10. Okoshi R, Ozaki T, Yamamoto H et al (2008) Activation of AMP-activated protein kinase induces p53-dependent apoptotic cell death in response to energetic stress. J Biol Chem 283:3979–3987PubMedCrossRefGoogle Scholar
  11. Qi J, Gong J, Zhao T et al (2008) Downregulation of AMP-activated protein kinase by Cidea-mediated ubiquitination and degradation in brown adipose tissue. EMBO J 27:1537–1548PubMedCrossRefGoogle Scholar
  12. Qin S (2007) Oxidative damage of retinal pigment epithelial cells and age-related macular degeneration. Drug Dev Res 68:213–225CrossRefGoogle Scholar
  13. Qin S, De Vries GW (2008) a2 But not a1 AMP-activated protein kinase mediates oxidative stress-induced inhibition of retinal pigment epithelium cell phagocytosis of photoreceptor outer segments. J Biol Chem 283:6744–6751PubMedCrossRefGoogle Scholar
  14. Qin S, Ni M, De Vries GW (2008) Implication of S-adenosylhomocysteine hydrolase in inhibition of TNF-a- and IL-1b-induced expression of inflammatory mediators by AICAR in RPE cells. Invest Ophthalmol Vis Sci 49:1274–1281PubMedCrossRefGoogle Scholar
  15. Qin S, Rodrigues GA (2008) Progress and perspectives on the role of RPE cell inflammatory responses in the development of age-related macular degeneration. J Inflamma Res 1:49–65CrossRefGoogle Scholar
  16. Qin S, Rodrigues GA (2010) Differential roles of AMPK a1 and AMPK a2 in regulating 4-HNE-induced RPE cell death and permeability. Exp Eye Res 91:818–824Google Scholar
  17. Scharl M, Paul G, Barrett KE et al (2009) AMP-activated protein kinase mediates the interferon-g-induced decrease in intestinal epithelial barrier function. J Biol Chem 284:27952–27963PubMedCrossRefGoogle Scholar
  18. Strauss O (2005) The retinal pigment epithelium in visual function. Physiol Rev 85:845–881PubMedCrossRefGoogle Scholar
  19. Streilein JW, Ma N, Wenkel H et al (2002) Immunobiology and privilege of neuronal retina and pigment epithelium transplants. Vision Res 42:487–495PubMedCrossRefGoogle Scholar
  20. Wagner TM, Mullally JE, Fitzpatrick FA (2006) Reactive lipid species from cyclooxygenase-2 inactivate tumor suppressor LKB1/STK11: cyclopentenone prostaglandins and 4-hydroxy-2-nonenal covalently modify and inhibit the AMP-kinase kinase that modulates cellular energy homeostasis and protein translation. J Biol Chem 281:2598–2604PubMedCrossRefGoogle Scholar
  21. Zhang L, Li J, Young LH et al (2006) AMP-activated protein kinase regulates the assembly of epithelial tight junctions. Proc Natl Acad Sci USA 103:17272–17277PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Biological SciencesRetinal Disease Research, Allergan, Inc.IrvineUSA

Personalised recommendations