Rat Group IIA Secreted Phospholipase A2 Binds to Cytochrome c Oxidase and Inhibits Its Activity: A Possible Episode in the Development of Alzheimer’s Disease
Abstract
:1. Introduction
2. Results
2.1. Recombinant rGIIA and rGIIA(D49S) Are Functional
2.2. rGIIA Binds to the Same Mitochondrial Target as the Neurotoxic Atx
2.3. rGIIA-Binding Protein in Mitochondria Is CCOX-II
2.4. rGIIA Inhibits CCOX Activity in Isolated Mitochondria
2.5. rGIIA(D49S) Internalizes into PC12 Cells and Colocalizes with Mitochondria
2.6. rGIIA(D49S) Showed Only Minor Effect on Mitochondrial Membrane Potential in PC12 Cells
2.7. rGIIA(D49S) Inhibited CCOX Activity in Rat Brain Tissue Sections
3. Discussion
4. Materials and Methods
4.1. Production and Characterization of the Recombinant Rat GIIA Proteins
4.2. Heterologous Competition Assay
4.3. Identification of rGIIA-Binding Protein in Porcine Cerebral Cortex Mitochondria
4.4. Culturing of PC12 Cells
4.5. Isolation of Mitochondria from PC12 Cells and Measurement of CCOX Activity
4.6. Fluorescence Confocal Microscopy Colocalization Study on PC12 Cells
4.7. Measurement of TMRM Fluorescence Intensity and Cell Death
4.8. Assessment of CCOX Activity in Rat Brain Tissue Sections
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Ivanušec, A.; Šribar, J.; Leonardi, A.; Zorović, M.; Živin, M.; Križaj, I. Rat Group IIA Secreted Phospholipase A2 Binds to Cytochrome c Oxidase and Inhibits Its Activity: A Possible Episode in the Development of Alzheimer’s Disease. Int. J. Mol. Sci. 2022, 23, 12368. https://doi.org/10.3390/ijms232012368
Ivanušec A, Šribar J, Leonardi A, Zorović M, Živin M, Križaj I. Rat Group IIA Secreted Phospholipase A2 Binds to Cytochrome c Oxidase and Inhibits Its Activity: A Possible Episode in the Development of Alzheimer’s Disease. International Journal of Molecular Sciences. 2022; 23(20):12368. https://doi.org/10.3390/ijms232012368
Chicago/Turabian StyleIvanušec, Adrijan, Jernej Šribar, Adrijana Leonardi, Maja Zorović, Marko Živin, and Igor Križaj. 2022. "Rat Group IIA Secreted Phospholipase A2 Binds to Cytochrome c Oxidase and Inhibits Its Activity: A Possible Episode in the Development of Alzheimer’s Disease" International Journal of Molecular Sciences 23, no. 20: 12368. https://doi.org/10.3390/ijms232012368