Collagen VI protects against neuronal apoptosis elicited by ultraviolet irradiation via an Akt/phosphatidylinositol 3-kinase signaling pathway

Neuroscience. 2011 Jun 2;183:178-88. doi: 10.1016/j.neuroscience.2011.03.057. Epub 2011 Apr 1.

Abstract

Collagen VI, one of the extracellular matrix proteins, has been implicated in regulating cell proliferation and reducing apoptosis in several different systems. However, the role of collagen VI in the central nervous system remains unclear. In this manuscript, we demonstrated that upon ultraviolet (UV) irradiation, mouse primary hippocampal neurons specifically up-regulate the expression of Col6a1, Col6a2, and Col6a3 mRNA and secreted collagen VI protein. Augmentation of collagen VI mRNA and protein after UV irradiation may have a neuroprotective role as suggested by the fact that extracellular supplying soluble collagen VI protein, but not other collagen proteins, reduced UV induced DNA damage, mitochondria dysfunction, and neurite shrinkage. We also tried to determine the signaling molecules that mediate the protective effect of collagen VI via Western blot and inhibitor analysis. After collagen VI treatment, UV irradiated neurons increased phosphorylation of Akt and decreased phosphorylation of JNK. Inhibiting Akt/phosphatidylinositol 3-kinases (PI3K) pathway diminished the protective effect of collagen VI. Our study suggested a potential protective mechanism by which neurons up-regulate collagen VI production under stress conditions to activate Akt/PI3K anti-apoptotic signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Cells, Cultured
  • Collagen Type VI / genetics
  • Collagen Type VI / metabolism
  • Collagen Type VI / pharmacology*
  • Dose-Response Relationship, Drug
  • Embryo, Mammalian
  • Enzyme Inhibitors / pharmacology
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / radiation effects
  • Hippocampus / cytology
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Inbred C57BL
  • Neurites / drug effects
  • Neurites / radiation effects
  • Neurons* / drug effects
  • Neurons* / enzymology
  • Neurons* / radiation effects
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Pregnancy
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects
  • Statistics, Nonparametric
  • Tetrazolium Salts
  • Thiazoles
  • Time Factors
  • Ultraviolet Rays / adverse effects*

Substances

  • Collagen Type VI
  • Enzyme Inhibitors
  • Tetrazolium Salts
  • Thiazoles
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • thiazolyl blue