April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Activation of Autophagy Induced By 7-ketocholesterol in Lens Epithelial Cells
Author Affiliations & Notes
  • J. V. Ferreira
    IBILI - Center of Ophthalmology, Coimbra, Portugal
  • H. Girao
    IBILI - Center of Ophthalmology, Coimbra, Portugal
  • P. Pereira
    IBILI - Center of Ophthalmology, Coimbra, Portugal
  • Footnotes
    Commercial Relationships  J.V. Ferreira, None; H. Girao, None; P. Pereira, None.
  • Footnotes
    Support  FCT PhD Fellowship SFRH/BD/32395/2006
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4374. doi:
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      J. V. Ferreira, H. Girao, P. Pereira; Activation of Autophagy Induced By 7-ketocholesterol in Lens Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4374.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Autophagy is the process by which proteins and subcellular organelles are delivered to the lysosome for degradation and is activated by several stress stimuli. It is currently considered a pro-survival mechanism that can degenerate in cell death upon chronic activation. It has been reported that autophagy doesn’t have a role in lens differentiation. Our aim is to show that 7-ketocholesterol, a cholesterol oxide, can activate macroautophagy in lens epithelial cells.

Methods: : SRA cells where incubated with 7-Ketocholesterol or 25-hydroxycholesterol (20 ug/ml) for 6 or 12 h, or maintained in nutrient deprivation for 12h. For Macroautophagy assessment cells were transfected with EGFP-LC3 plasmid. Autophagic vesicle formation was assessed by confocal microscopy. LC3 processing was measured by western blot with antibodies against GFP. Akt and p-Akt levels where accessed by western blot with specific antibodies.

Results: : 7-Ketocholesterol induces the formation of autophagic vesicles and the processing of the LC3-I into LC3-II, both hallmarks of Macroautophagy, an effected not mimicked by 25-Hydroxycholesterol. 7-Ketocholesterol, but not 25-Hydroxycholesterol, can also decrease Akt and p-Akt levels. The effect of 7-Ketocholesterol can be partially reverted by the overexpression of a constitutively active Akt in SRA cells.

Conclusions: : SRA cells undergo autophagy activation when exposed to 7-Ketocholesterol, possibly as a cell survival mechanism upon 7-Ketocholesterol induced stress. Chronic exposure may lead to autophagic cell death. 7-Ketocholestrol induced activation of Macroautophagy seems to be partially related to the PI3K-Akt-mTOR pathway.

Keywords: lipids 

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