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Hibernation-induction peptide and cell death: [D-Ala2,D-Leu5]enkephalin blocks Bax-related apoptotic processes
1Cellular Pathobiology Unit, Cellular Neurobiology Research Branch, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA.
Abstract:
The psychostimulant methamphetamine, both in vivo and in vitro, caused a mitochondrial cytochrome c release, the translocation of Bax from cytosol into mitochondrion, and the oligomerization of Bax. These effects by methamphetamine were blocked by a neuroprotective and hibernation-induction delta opioid peptide [D-Ala2,D-Leu5]enkephalin (DADLE). These results suggest that methamphetamine causes apoptosis by affecting the dynamics of Bax and that the neuroprotective property of DADLE may be due partly to its ability to potently block Bax-related apoptotic processes.
Insights
Methamphetamine triggers apoptosis by altering Bax protein dynamics, leading to cell death. The neuroprotective peptide DADLE effectively blocks these methamphetamine-induced apoptotic processes.
Area of Science:
- Neuroscience
- Molecular Biology
- Toxicology
Background:
- Methamphetamine is a psychostimulant with known neurotoxic effects.
- Apoptosis, or programmed cell death, is a critical cellular process.
- Mitochondrial pathways, involving proteins like Bax, are key regulators of apoptosis.
Purpose of the Study:
- To investigate the effects of methamphetamine on mitochondrial apoptotic pathways.
- To determine the role of the Bax protein in methamphetamine-induced apoptosis.
- To evaluate the neuroprotective potential of [D-Ala2,D-Leu5]enkephalin (DADLE) against methamphetamine toxicity.
Main Methods:
- In vivo and in vitro experiments were conducted.
- Mitochondrial cytochrome c release was measured.
- Bax protein translocation, oligomerization, and effects of DADLE were analyzed.
Main Results:
- Methamphetamine induced mitochondrial cytochrome c release.
- Methamphetamine caused Bax translocation from cytosol to mitochondria and Bax oligomerization.
- DADLE significantly blocked these methamphetamine-induced apoptotic events.
Conclusions:
- Methamphetamine induces apoptosis by disrupting Bax protein dynamics.
- DADLE exhibits neuroprotective properties by inhibiting Bax-related apoptotic pathways.
- These findings highlight a novel mechanism of methamphetamine neurotoxicity and a potential therapeutic target.