Stimulatory effect of vitamin C on autophagy in glial cells.
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.
Martin
Antonio
A
Neuroscience Laboratory, HNRC on Aging, Tufts University, Boston, Massachusetts, USA.
Joseph
James A
JA
Cuervo
Ana Maria
AM
D001205:Ascorbic Acid / Q000493:pharmacokinetics / Q000494:pharmacology*; D001253:Astrocytes / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008247:Lysosomes / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D009457:Neuroglia / Q000737:chemistry / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*
D011506:Proteins; D010447:Peptide Hydrolases; D001205:Ascorbic Acid