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 Posted: Thu Oct 02, 2008 8:01 pm Post subject: Stimulatory effect of vitamin C on autophagy in glial cells |
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Vitamin C may have this effect due to it>s ability to inhibit transfer
of ferritin into lysosomes thereby decreasing intralysosomal iron.
J Neurochem. 2002 Aug;82(3):538-49. Links
Stimulatory effect of vitamin C on autophagy in glial cells.Martin A,
Joseph JA, Cuervo AM.
Neuroscience Laboratory, HNRC on Aging, Tufts University, Boston,
Massachusetts, USA.
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.
PMID: 12153478 [PubMed - indexed for MEDLINE]
Related ArticlesProtective effect of vitamin C against the ethanol
mediated toxic effects on human brain glial cells. [J Nutr Biochem.
2003] The role of the intralysosomal pH in the control of autophagic
proteolytic flux in rat hepatocytes. [Eur J Biochem. 1996] Vitamin C
uptake and recycling among normal and tumor cells from the central
nervous system. [J Neurosci Res. 2005] Ascorbic acid inhibits
lysosomal autophagy of ferritin. [J Biol Chem. 1987] Potential
compensatory responses through autophagic/lysosomal pathways in
neurodegenerative diseases. [Autophagy. 2006] » See all Related
Articles... |
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| Posted: Thu Oct 02, 2008 8:08 pm Post subject: Re: Stimulatory effect of vitamin C on autophagy in glial ce |
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Am J Clin Nutr. 1991 Dec;54(6 Suppl):1188S-1192S. Links
Ascorbic acid and iron metabolism: alterations in lysosomal
function.Hoffman KE, Yanelli K, Bridges KR.
Department of Medicine, Brigham and Women>s Hospital, Harvard Medical
School, Boston, MA 02115.
Iron is essential to cell metabolism but promotes free radical damage
to membranes and lipids. Therefore, excess intracellular iron is
stored within the shell of hollow ferritin molecules until needed for
metabolic use. Ascorbate retards ferritin degradation and increases
iron bioavailability. The vitamin stabilizes the iron cores of
ferritin in cells prelabeled with 59Fe. [35S]Methionine labeling
demonstrates that this enhanced stability of the iron cores results
from delayed degradation of the ferritin shells. Subcellular
fractionation of 59Fe-labeled cells by use of a Sepharose CL-6B column
shows that ascorbate significantly delays the shift of ferritin label
from the cytosolic to the lysosomal compartment. Monomeric ferritin
shells in the cytoplasm gradually form clusters that bind to
lysosomes. Single ferritin shells do not. Ascorbate does not affect
the conversion of cytoplasmic ferritin monomers to clusters but
greatly retards the autophagic uptake of ferritin clusters into
lysosomes.
PMID: 1962568 [PubMed - indexed for MEDLINE]
Related ArticlesAscorbic acid inhibits lysosomal autophagy of
ferritin. [J Biol Chem. 1987] The effects of ascorbic acid on the
intracellular metabolism of iron and ferritin. [J Biol Chem. 1986]
Subcellular localization of ferritin and iron taken up by rat
hepatocytes. [Biochem J. 1989] Uptake of ferritin and iron bound to
ferritin by rat hepatocytes: modulation by apotransferrin, iron
chelators and chloroquine. [Biochim Biophys Acta. 1989] Iron in
cytosolic ferritin can be recycled through lysosomal degradation in
human fibroblasts. [Biochem J. 1998] » See all Related Articles...
FULL TEXT
http://www.ajcn.org/cgi/reprint/54/6/1188S |
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| Posted: Thu Oct 02, 2008 8:13 pm Post subject: Re: Stimulatory effect of vitamin C on autophagy in glial ce |
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So Vitamin C may help to inhibit lipofuscin.
Arch Biochem Biophys. 2007 Jun 15;462(2):220-30. Epub 2007 Feb 2.
Links
Autophagy, ageing and apoptosis: the role of oxidative stress and
lysosomal iron.Kurz T, Terman A, Brunk UT.
Division of Pharmacology, Faculty of Health Sciences, Linköping
University, Linköping, Sweden.
As an outcome of normal autophagic degradation of ferruginous
materials, such as ferritin and mitochondrial metalloproteins, the
lysosomal compartment is rich in labile iron and, therefore, sensitive
to the mild oxidative stress that cells naturally experience because
of their constant production of hydrogen peroxide. Diffusion of
hydrogen peroxide into the lysosomes results in Fenton-type reactions
with the formation of hydroxyl radicals and ensuing peroxidation of
lysosomal contents with formation of lipofuscin that amasses in long-
lived postmitotic cells. Lipofuscin is a non-degradable polymeric
substance that forms at a rate that is inversely related to the
average lifespan across species and is built up of aldehyde-linked
protein residues. The normal accumulation of lipofuscin in lysosomes
seems to reduce autophagic capacity of senescent postmitotic cells--
probably because lipofuscin-loaded lysosomes continue to receive newly
formed lysosomal enzymes, which results in lack of such enzymes for
autophagy. The result is an insufficient and declining rate of
autophagic turnover of worn-out and damaged cellular components that
consequently accumulate in a way that upsets normal metabolism. In the
event of a more substantial oxidative stress, enhanced formation of
hydroxyl radicals within lysosomes jeopardizes the membrane stability
of particularly iron-rich lysosomes, specifically of
autophagolysosomes that have recently participated in the degradation
of iron-rich materials. For some time, the rupture of a limited number
of lysosomes has been recognized as an early upstream event in many
cases of apoptosis, particularly oxidative stress-induced apoptosis,
while necrosis results from a major lysosomal break. Consequently, the
regulation of the lysosomal content of redox-active iron seems to be
essential for the survival of cells both in the short- and the long-
term.
PMID: 17306211 [PubMed - indexed for MEDLINE] |
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| Posted: Thu Oct 02, 2008 8:18 pm Post subject: Re: Stimulatory effect of vitamin C on autophagy in glial ce |
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Histochem Cell Biol. 2008 Apr;129(4):389-406. Epub 2008 Feb 8. Links
Lysosomes in iron metabolism, ageing and apoptosis.Kurz T, Terman A,
Gustafsson B, Brunk UT.
Division of Pharmacology, Faculty of Health Sciences, Linköping
University, Linköping, Sweden.
The lysosomal compartment is essential for a variety of cellular
functions, including the normal turnover of most long-lived proteins
and all organelles. The compartment consists of numerous acidic
vesicles (pH approximately 4 to 5) that constantly fuse and divide. It
receives a large number of hydrolases ( approximately 50) from the
trans-Golgi network, and substrates from both the cells' outside
(heterophagy) and inside (autophagy). Many macromolecules contain iron
that gives rise to an iron-rich environment in lysosomes that recently
have degraded such macromolecules. Iron-rich lysosomes are sensitive
to oxidative stress, while 'resting' lysosomes, which have not
recently participated in autophagic events, are not. The magnitude of
oxidative stress determines the degree of lysosomal destabilization
and, consequently, whether arrested growth, reparative autophagy,
apoptosis, or necrosis will follow. Heterophagy is the first step in
the process by which immunocompetent cells modify antigens and produce
antibodies, while exocytosis of lysosomal enzymes may promote tumor
invasion, angiogenesis, and metastasis. Apart from being an essential
turnover process, autophagy is also a mechanism by which cells will be
able to sustain temporary starvation and rid themselves of
intracellular organisms that have invaded, although some pathogens
have evolved mechanisms to prevent their destruction. Mutated
lysosomal enzymes are the underlying cause of a number of lysosomal
storage diseases involving the accumulation of materials that would be
the substrate for the corresponding hydrolases, were they not
defective. The normal, low-level diffusion of hydrogen peroxide into
iron-rich lysosomes causes the slow formation of lipofuscin in long-
lived postmitotic cells, where it occupies a substantial part of the
lysosomal compartment at the end of the life span. This seems to
result in the diversion of newly produced lysosomal enzymes away from
autophagosomes, leading to the accumulation of malfunctioning
mitochondria and proteins with consequent cellular dysfunction. If
autophagy were a perfect turnover process, postmitotic ageing and
several age-related neurodegenerative diseases would, perhaps, not
take place.
PMID: 18259769 [PubMed - indexed for MEDLINE] |
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