CNS myelin structural modification induced in vitro by phospholipases A2.
Pablo J Yunes Quartino1, Julio M Pusterla1, Victor M Galván Josa2
1Departamento de Química Biológica-CIQUIBIC (CONICET), Facultad de Ciencias Químicas, Universidad de Nacional de Córdoba, Haya de la Torre S/N, X5000HUA, Córdoba, Argentina.
Biochimica Et Biophysica Acta
|October 31, 2015
Summary
Secreted phospholipases (sPLA2) alter myelin structure by increasing spacing between membranes and disorder, while preserving overall lamellar integrity. Hydrolysis occurred across all tested sPLA2 enzyme isoforms.
Area of Science:
- Neuroscience
- Biochemistry
- Structural Biology
Background:
- Myelin, the insulating membrane sheath around axons, is crucial for neural function.
- Myelin damage is implicated in neurodegenerative diseases like multiple sclerosis.
- Phospholipases are enzymes that can hydrolyze membrane components.
Purpose of the Study:
- To investigate the structural impact of secreted phospholipases (sPLA2) on isolated myelin.
- To understand the hydrolysis mechanism of myelin by different sPLA2 isoforms.
Main Methods:
- Small-angle X-ray scattering (SAXS) to analyze myelin structure.
- Langmuir film experiments to monitor myelin hydrolysis at an air/water interface.
- Treatment of isolated myelin with sPLA2 from various sources (cobra venom, bee venom, pig pancreas).
Main Results:
- SAXS revealed preserved lamellar myelin structure with enlarged inter-membrane spacing in some regions.
- Enhanced peak associated with membrane asymmetry and decreased coherence length indicating increased disorder.
- Langmuir films showed hydrolysis by all tested sPLA2s, evidenced by decreased surface electric potential.
- No significant qualitative differences in hydrolysis were observed between sPLA2 isoforms.
Conclusions:
- Secreted phospholipases induce structural changes in myelin, including increased disorder and altered membrane spacing.
- Myelin hydrolysis by sPLA2 is a common mechanism across different enzyme isoforms.
- These findings provide insights into myelin pathology in neurodegenerative conditions.
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