STARVATION-INDUCED AUTOPHAGOCYTOSIS PARADOXICALLY DECREASES THE SUSCEPTIBILITY TO OXIDATIVE STRESS OF THE EXTREMELY OXIDATIVE STRESS-SENSITIVE NIT INSULINOMA CELLS
Bt. Olejnicka et al., STARVATION-INDUCED AUTOPHAGOCYTOSIS PARADOXICALLY DECREASES THE SUSCEPTIBILITY TO OXIDATIVE STRESS OF THE EXTREMELY OXIDATIVE STRESS-SENSITIVE NIT INSULINOMA CELLS, Redox report, 3(5-6), 1997, pp. 311-318
Glucose and amino acid starvation of cells in culture generally enhanc
es their sensitivity to oxidative stress. This is explained by compens
atory autophagocytosis, which results in increased amounts of lysosoma
l low-molecular-weight, redox-active iron, due to the degradation of m
etallo-proteins, with a potential increase in iron-catalyzed, intralys
osomal oxidative reactions. Such reactions diminish the stability of l
ysosomal membranes, with resultant leakage of hydrolytic enzymes into
the cytosol and ensuing cellular degeneration, often of apoptotic type
. However, starvation of NIT insulinoma cells, which are normally rema
rkably sensitive to oxidative stress, actually attenuated the sensitiv
ity to such stress, We found that starved NIT cells rapidly synthesize
d ferritin. Moreover, ferritin was found to be autophagocytosed, and t
he lysosomes were stabilized, as assayed by the acridine orange reloca
tion test. We hypothesize that compensatory autophagocytosis during st
arvation increases the cytosolic pool of redox-active iron, as a refle
ction of enhanced transportation of low-molecular-weight iron from aut
ophagic lysosomes to the cytosol, resulting in ferritin induction. The
newly formed ferritin would, in turn, become autophagocytosed and bin
d redox-active lysosomal iron in a non-redox-active form. We also sugg
est that the proposed mechanism may be a way for oxidative stress-sens
itive cells to compensate partly for their failing capacity to degrade
hydrogen peroxide before it leaks into the acidic vacuolar apparatus
and induces intralysosomal oxidative stress. The insulin-producing bet
a cell may belong to this type of cells.