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Stimulatory effect of vitamin C on autophagy in glial cells
Antonio Martin1, James A Joseph, Ana Maria Cuervo
1Neuroscience Laboratory, HNRC on Aging, Tufts University, Boston, Massachusetts, USA.
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.
Insights
Vitamin C (ascorbate) enhances protein degradation in human glial cells by boosting lysosomal activity. This process may help reduce harmful protein buildup in neurodegenerative diseases.
Area of Science:
- Cell Biology
- Neuroscience
- Biochemistry
Background:
- Intracellular accumulation of damaged proteins is linked to neurodegenerative diseases.
- Enhancing protein degradation systems may mitigate these pathologies.
Purpose of the Study:
- To investigate the effect of vitamin C (ascorbate) on intracellular protein turnover in human astrocyte glial cells.
- To determine if vitamin C influences protein synthesis or degradation pathways.
Main Methods:
- Cultured human astrocyte glial cells were supplemented with physiological concentrations of vitamin C.
- Protein synthesis and degradation rates were measured.
- Lysosomal activity and intralysosomal pH were analyzed.
Main Results:
- Vitamin C did not affect protein synthesis.
- Vitamin C significantly increased the rate of protein degradation via lysosomal pathways (autophagic and heterophagic).
- Vitamin C lowered and stabilized intralysosomal pH, optimizing lysosomal hydrolase activity.
Conclusions:
- Vitamin C enhances the cellular protein degradation machinery, specifically lysosomal function.
- This ascorbate-induced enhancement of proteolysis offers a potential therapeutic strategy for diseases involving abnormal protein aggregation.
- Targeting lysosomal pH with vitamin C may be a viable approach to combat neurodegeneration.