INVESTIGADORES
GENTILI Claudia Rosana
artículos
Título:
Docosahexaenoic acid prevents apoptosis of retina photoreceptors by activating the ERK/MAPK pathway
Autor/es:
OLGA LORENA GERMAN; MARIA FERNANDA INSUA; CLAUDIA GENTILI; NORA P. ROTSTEIN; LUIS E. POLITI
Revista:
JOURNAL OF NEUROCHEMISTRY
Editorial:
International Society for Neurochemistry
Referencias:
Lugar: USA; Año: 2006 vol. 98 p. 1507 - 1520
ISSN:
0022-3042
Resumen:
Identifying the trophic factors for retina photoreceptors and
the intracellular pathways activated to promote cell survival
is crucial for treating retina neurodegenerative diseases.
Docosahexaenoic acid (DHA), the major retinal polyunsaturated
fatty acid, prevents photoreceptor apoptosis
during early development in vitro, and upon oxidative stress.
However, the signaling mechanisms activated by DHA are
still unclear. We investigated whether the extracellular signal
regulated kinase (ERK)/mitogen-activated protein kinase
(MAPK) or the phosphatidylinositol-3-kinase (PI3K) pathway
participated in DHA protection. 1,4-Diamino-2,3-dicyano-1,4-
bis(2-aminophynyltio) butadiene (U0126), a specific MEK
inhibitor, completely blocked the DHA anti-apoptotic effect.
DHA rapidly increased ERK phosphorylation in photoreceptors,
whereas U0126 blocked this increase. U0126 hindered
DHA prevention of mitochondrial depolarization, and blocked
the DHA-induced increase in opsin expression. On the
contrary, PI3K inhibitors did not diminish the DHA protective
effect. DHA promoted the early expression of Bcl-2, decreased
Bax expression and reduced caspase-3 activation
in photoreceptors. These results suggest that DHA exclusively
activates the ERK/MAPK pathway to promote photoreceptor
survival during early development in vitro and upon
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
the DHA-induced increase in opsin expression. On the
contrary, PI3K inhibitors did not diminish the DHA protective
effect. DHA promoted the early expression of Bcl-2, decreased
Bax expression and reduced caspase-3 activation
in photoreceptors. These results suggest that DHA exclusively
activates the ERK/MAPK pathway to promote photoreceptor
survival during early development in vitro and upon
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
the DHA-induced increase in opsin expression. On the
contrary, PI3K inhibitors did not diminish the DHA protective
effect. DHA promoted the early expression of Bcl-2, decreased
Bax expression and reduced caspase-3 activation
in photoreceptors. These results suggest that DHA exclusively
activates the ERK/MAPK pathway to promote photoreceptor
survival during early development in vitro and upon
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
Keywords: Bcl-2, docosahexaenoic acid, extracellular signalregulated
kinase signalling pathway, mitochondrial depolarization,
photoreceptor, survival.
kinase signalling pathway, mitochondrial depolarization,
photoreceptor, survival.
Bcl-2, docosahexaenoic acid, extracellular signalregulated
kinase signalling pathway, mitochondrial depolarization,
photoreceptor, survival.
However, the signaling mechanisms activated by DHA are
still unclear. We investigated whether the extracellular signal
regulated kinase (ERK)/mitogen-activated protein kinase
(MAPK) or the phosphatidylinositol-3-kinase (PI3K) pathway
participated in DHA protection. 1,4-Diamino-2,3-dicyano-1,4-
bis(2-aminophynyltio) butadiene (U0126), a specific MEK
inhibitor, completely blocked the DHA anti-apoptotic effect.
DHA rapidly increased ERK phosphorylation in photoreceptors,
whereas U0126 blocked this increase. U0126 hindered
DHA prevention of mitochondrial depolarization, and blocked
the DHA-induced increase in opsin expression. On the
contrary, PI3K inhibitors did not diminish the DHA protective
effect. DHA promoted the early expression of Bcl-2, decreased
Bax expression and reduced caspase-3 activation
in photoreceptors. These results suggest that DHA exclusively
activates the ERK/MAPK pathway to promote photoreceptor
survival during early development in vitro and upon
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
the DHA-induced increase in opsin expression. On the
contrary, PI3K inhibitors did not diminish the DHA protective
effect. DHA promoted the early expression of Bcl-2, decreased
Bax expression and reduced caspase-3 activation
in photoreceptors. These results suggest that DHA exclusively
activates the ERK/MAPK pathway to promote photoreceptor
survival during early development in vitro and upon
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
the DHA-induced increase in opsin expression. On the
contrary, PI3K inhibitors did not diminish the DHA protective
effect. DHA promoted the early expression of Bcl-2, decreased
Bax expression and reduced caspase-3 activation
in photoreceptors. These results suggest that DHA exclusively
activates the ERK/MAPK pathway to promote photoreceptor
survival during early development in vitro and upon
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
Keywords: Bcl-2, docosahexaenoic acid, extracellular signalregulated
kinase signalling pathway, mitochondrial depolarization,
photoreceptor, survival.
kinase signalling pathway, mitochondrial depolarization,
photoreceptor, survival.
Bcl-2, docosahexaenoic acid, extracellular signalregulated
kinase signalling pathway, mitochondrial depolarization,
photoreceptor, survival.
in vitro, and upon oxidative stress.
However, the signaling mechanisms activated by DHA are
still unclear. We investigated whether the extracellular signal
regulated kinase (ERK)/mitogen-activated protein kinase
(MAPK) or the phosphatidylinositol-3-kinase (PI3K) pathway
participated in DHA protection. 1,4-Diamino-2,3-dicyano-1,4-
bis(2-aminophynyltio) butadiene (U0126), a specific MEK
inhibitor, completely blocked the DHA anti-apoptotic effect.
DHA rapidly increased ERK phosphorylation in photoreceptors,
whereas U0126 blocked this increase. U0126 hindered
DHA prevention of mitochondrial depolarization, and blocked
the DHA-induced increase in opsin expression. On the
contrary, PI3K inhibitors did not diminish the DHA protective
effect. DHA promoted the early expression of Bcl-2, decreased
Bax expression and reduced caspase-3 activation
in photoreceptors. These results suggest that DHA exclusively
activates the ERK/MAPK pathway to promote photoreceptor
survival during early development in vitro and upon
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
the DHA-induced increase in opsin expression. On the
contrary, PI3K inhibitors did not diminish the DHA protective
effect. DHA promoted the early expression of Bcl-2, decreased
Bax expression and reduced caspase-3 activation
in photoreceptors. These results suggest that DHA exclusively
activates the ERK/MAPK pathway to promote photoreceptor
survival during early development in vitro and upon
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
the DHA-induced increase in opsin expression. On the
contrary, PI3K inhibitors did not diminish the DHA protective
effect. DHA promoted the early expression of Bcl-2, decreased
Bax expression and reduced caspase-3 activation
in photoreceptors. These results suggest that DHA exclusively
activates the ERK/MAPK pathway to promote photoreceptor
survival during early development in vitro and upon
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
oxidative stress. This leads to the regulation of Bcl-2 and
Bax expression, thus preserving mitochondrial membrane
potential and inhibiting caspase activation. Hence, DHA, a
lipid trophic factor, promotes photoreceptor survival and
differentiation by activating the same signaling pathways
triggered by peptidic trophic factors.
Keywords: Bcl-2, docosahexaenoic acid, extracellular signalregulated
kinase signalling pathway, mitochondrial depolarization,
photoreceptor, survival.
kinase signalling pathway, mitochondrial depolarization,
photoreceptor, survival.
Bcl-2, docosahexaenoic acid, extracellular signalregulated
kinase signalling pathway, mitochondrial depolarization,
photoreceptor, survival.