Vitamin E as a novel enhancer of macroautophagy in rat hepatocytes and H4-II-E cells

Md Razaul Karim, Shinobu Fujimura, Motoni Kadowaki

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Autophagy is an intracellular bulk degradation process induced by nutrient starvation, and contributes to macromolecular turnover and rejuvenation of cellular organelles. We demonstrated that vitamin E was a novel nutritional enhancer of autophagy in freshly isolated rat hepatocytes and rat hepatoma H4-II-E cells. Supplementation of fresh hepatocytes with vitamin E (up to 100 μM) increased proteolysis significantly in the presence or absence of amino acids in a dose-dependent manner. The cytosolic LC3 ratio, a newly established index of autophagic flux, was significantly increased by vitamin E, strongly suggesting that the possible site of action is the LC3 conversion step, an early step in autophagosome formation. A typical antioxidant, α-lipoic acid, exerted autophagy suppression, while H2O2 stimulated autophagy. It is conceivable that autophagy was stimulated by oxidative stress and this stimulation was cancelled by cellular antioxidative effects. However, in our studies, vitamin E could have enhanced autophagy over-stimulation by H2O2, rather than suppress it. From these results, using a new cytosolic LC3 ratio, vitamin E increases autophagy by accelerating LC3 conversion through a new signaling pathway, emerging as a novel enhancer of autophagy.

Original languageEnglish (US)
Pages (from-to)981-987
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number4
StatePublished - Apr 16 2010
Externally publishedYes


  • Antioxidation
  • Autophagy
  • Cytosolic LC3 ratio
  • Oxidative stress
  • Vitamin E


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