INVESTIGADORES
LAROCCA Maria Cecilia
artículos
Título:
Protein kinase A signals apoptotic activation in glucose-deprived
Autor/es:
FERRETI AC; MATTALONI SM; OCHOA EJ; LAROCCA MC; FAVRE C
Revista:
APOPTOSIS
Editorial:
SPRINGER
Referencias:
Año: 2012 vol. 17 p. 475 - 491
ISSN:
1360-8185
Resumen:
Glucose deprivation entails oxidative stress and
apoptosis in diverse cell types. Liver tissue shows high
tolerance to nutritional stress, however regulation of survival
in normal hepatocytes subjected to glucose restriction
is unclear. We assessed the survival response of cultured
hepatocytes subjected to glucose deprivation and analyzed
the putative participation of protein kinase A (PKA) in this
response. Six hours glucose deprivation induced a PKA
dependent activation of apoptosis in cultured hepatocytes,
without having an impact on non apoptotic death. Apoptotic
activation associated to glucose restriction was secondary
to an imbalance in cellular reactive oxygen species
(ROS). In this condition, PKA inhibition led to an early
prevention in mitochondrial ROS production and a late
increase in scavenging enzymes transcript levels. These
results supported the hypothesis that PKA could modulate
glucose deprivation induced apoptotic activation by conditioning
mitochondrial ROS production during glucose
fasting. We presented additional evidence sustaining this
model: First, glucose withdrawal led to a 95% increase in
mitochondrial cAMP levels in cultured hepatocytes; second,
activation of PKA significantly augmented hepatic
mitochondrial ROS generation, whereas PKA inhibition
elicited the opposite effect. Mitochondrial PKA signaling,
previously proposed as an autonomic pathway adjusting
respiration rate, emerges as a mechanism of controlling cell
survival during glucose restriction.