Related Experiment Videos
Herp stabilizes neuronal Ca2+ homeostasis and mitochondrial function during endoplasmic reticulum stress
Sic L Chan1, Weiming Fu, Peisu Zhang
1Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. chanst@grc.nia.nih.gov
The Journal of Biological Chemistry
|April 23, 2004
Summary
Herp protein protects neurons from endoplasmic reticulum (ER) stress-induced death. It stabilizes calcium levels and preserves mitochondrial function, acting as a key neuroprotective factor.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Endoplasmic reticulum (ER) stress triggers cellular protective or death responses.
- Herp, a 54 kDa ER membrane protein, is stress-responsive in non-neuronal cells.
Purpose of the Study:
- Investigate Herp's presence and regulation in neurons.
- Determine Herp's role in neuronal response to ER stress and apoptosis.
Main Methods:
- Studied Herp expression in developing and adult brain neurons.
- Analyzed Herp's regulation by ER stress levels (sublethal vs. lethal).
- Investigated Herp's interaction with caspases, mitochondrial function, and calcium signaling.
Main Results:
- Herp is present and regulated by ER stress in neurons.
- Lethal ER stress decreases Herp via caspase cleavage before cell death.
- Herp overexpression promotes neuronal survival by stabilizing ER Ca(2+) and mitochondria.
- Herp inhibits JNK/c-Jun and caspase 12 activation, but not ER chaperone induction.
Conclusions:
- Herp plays a crucial neuroprotective role against ER stress.
- Herp stabilizes ER calcium homeostasis and mitochondrial function.
- Herp modulates neuronal calcium signaling and caspase activation pathways.