Abstract
The unfolded protein response (UPR) is a specific cellular process that allows the cell to cope with the overload of unfolded/misfolded proteins in the endoplasmic reticulum (ER). ER stress is commonly associated with degenerative pathologies, but its role in disease progression is still a matter for debate. Here, we found that mutations in the ER-resident chaperone, neither inactivation nor afterpotential A (NinaA), lead to mild ER stress, protecting photoreceptor neurons from various death stimuli in adult Drosophila. In addition, Drosophila S2 cultured cells, when pre-exposed to mild ER stress, are protected from H(2)O(2), cycloheximide- or ultraviolet-induced cell death. We show that a specific ER-mediated signal promotes antioxidant defences and inhibits caspase-dependent cell death. We propose that an immediate consequence of the UPR not only limits the accumulation of misfolded proteins but also protects tissues from harmful exogenous stresses.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Apoptosis / drug effects
-
Caspases / metabolism
-
Cell Line
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / physiology
-
Drosophila Proteins / genetics
-
Drosophila Proteins / physiology
-
Drosophila melanogaster / cytology
-
Drosophila melanogaster / drug effects
-
Drosophila melanogaster / physiology*
-
Endoplasmic Reticulum / metabolism
-
Endoplasmic Reticulum / physiology*
-
Hydrogen Peroxide / pharmacology
-
Membrane Proteins / genetics
-
Membrane Proteins / physiology
-
Molecular Chaperones / genetics
-
Molecular Chaperones / physiology
-
Mutation
-
Photoreceptor Cells / cytology
-
Photoreceptor Cells / drug effects
-
Photoreceptor Cells / metabolism
-
Retina / cytology
-
Retina / drug effects
-
Retina / metabolism
-
Retinal Degeneration / genetics
-
Retinal Degeneration / metabolism*
-
Reverse Transcriptase Polymerase Chain Reaction
-
Stress, Physiological / genetics
-
Stress, Physiological / physiology*
Substances
-
DNA-Binding Proteins
-
Drosophila Proteins
-
Membrane Proteins
-
Molecular Chaperones
-
Xbp1 protein, Drosophila
-
ninaA protein, Drosophila
-
Hydrogen Peroxide
-
Caspases