STIMULATORY EFFECT OF VITAMIN C ON AUTOPHAGY IN GLIAL CELLS

Authors: MARTIN, ANTONIO - HNRCA; JOSEPH, JAMES - USDA; CUERVO, ANA MARIA - ALBERT EINSTEIN COLL OF M

Submitted to: Journal of Neurochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/15/2002
Publication Date: 6/1/2002
Citation: MARTIN, A., JOSEPH, J., CUERVO, A. STIMULATORY EFFECT OF VITAMIN C ON AUTOPHAGY IN GLIAL CELLS. JOURNAL OF NEUROCHEMISTRY. 82: 538-549,2002.

Interpretive Summary: Accumulation of damaged or abnormal proteins inside the cell is a common event associated with numerous neurodegenerative diseases and other age-related pathologies. In this study we investigated ways to increase the efficiency of the systems involved in the degradation of modified proteins to increase the removal of abnormal proteins. This is important because reducing the amount of abnormal proteins inside the cell is beneficial in lessening the severity or development of pathologies associated with decline in brain function. In this study we have used human brains cells called astrocyte to investigate the effect of vitamin C on the degradation of proteins. Supplementation of the brain cells with physiological (normal) concentrations of vitamin C did not affect protein synthesis, but did increase the rate (speed) of protein degradation by the intracellular cellular organelles called lysosomes. Vitamin C accelerated the degradation of proteins by the lysosomes. At the vitamin C doses used, which correspond to what is found in vivo under physiological conditions, vitamin C lowered and stabilized the intra-lysosomal conditions like the acidity, at values that result in maximum activation of the lysosomal function and its capability to degrade proteins.

Technical Abstract: Intracellular accumulation of damaged or abnormal proteins is a common event associated with numerous neurodegenerative diseases and other age-related pathologies. Increasing the activity of the intracellular proteolytic systems normally responsible for the removal of these abnormal proteins might be beneficial in lessening the severity or development of those pathologies. In this study we have used human astrocyte glial cells to investigate the effect of vitamin C (ascorbate) on the intracellular turnover of proteins. Supplementation of the culture medium with physiological concentrations of vitamin C did not affect protein synthesis, but did increase the rate of protein degradation by lysosomes. Vitamin C accelerated the degradation of intra- and extracellular proteins targeted to the lysosomal lumen by autophagic and heterophagic pathways. At the doses analyzed, vitamin C lowered and stabilized the acidic intralysosomal pH at values that result in maximum activation of the lysosomal hydrolases.