Next Article in Journal
Role of Cadherins in Cancer—A Review
Next Article in Special Issue
Alpha-B-Crystallin Effect on Mature Amyloid Fibrils: Different Degradation Mechanisms and Changes in Cytotoxicity
Previous Article in Journal
Molecular Mechanisms and Emerging Therapeutics for Osteoporosis
Previous Article in Special Issue
Dietary Intake of Rosmarinic Acid Increases Serum Inhibitory Activity in Amyloid A Aggregation and Suppresses Deposition in the Organs of Mice
 
 
Article

Development of Conformational Antibodies to Detect Bcl-xL’s Amyloid Aggregates in Metal-Induced Apoptotic Neuroblastoma Cells

1
Laboratoire de Chimie et Biologie des Métaux, UMR5249 Université Grenoble Alpes, CNRS, CEA, 17 rue des Martyrs, CEDEX 9, 38054 Grenoble, France
2
Département d’immunologie et biologie cellulaire, Pavillon de recherche appliquée sur le cancer, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada
3
Faculté des Sciences d’El Jadida, Université Chouaib Doukkali, El Jadida 24000, Maroc
4
Laboratory «Innovative Technologies for Detection and Diagnostics» CEA-Marcoule, DRF-Li2D PRAE Marcel Boiteux, BP 1717, 30200 Bagnols-sur-Cèze CEDEX, France
5
Chemistry and Structural Biology Department, Institut Pasteur, UMR CNRS 3528, CEDEX 15, 75724 Paris, France
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(20), 7625; https://doi.org/10.3390/ijms21207625
Received: 4 September 2020 / Revised: 6 October 2020 / Accepted: 10 October 2020 / Published: 15 October 2020
Bcl-xL, a member of the Bcl-2 family, is a pro-survival protein involved in apoptosis regulation. We have previously reported the ability of Bcl-xL to form various types of fibers, from native to amyloid conformations. Here, we have mimicked the effect of apoptosis-induced caspase activity on Bcl-xL by limited proteolysis using trypsin. We show that cleaved Bcl-xL (ΔN-Bcl-xL) forms fibers that exhibit the features of amyloid structures (BclxLcf37). Moreover, three monoclonal antibodies (mAbs), produced by mouse immunization and directed against ΔN-Bcl-xL or Bcl-xL fibers, were selected and characterized. Our results show that these mAbs specifically target ΔN-Bcl-xL in amyloid fibers in vitro. Upon metal-stress-induced apoptosis, these mAbs are able to detect the presence of Bcl-xL in amyloid aggregates in neuroblastoma SH-SY5Y cell lines. In conclusion, these specific mAbs directed against amyloidogenic conformations of Bcl-xL constitute promising tools for studying, in vitro and in cellulo, the contribution of Bcl-xL in apoptosis. These mAbs may further help in developing new diagnostics and therapies, considering Bcl-xL as a strategic target for treating brain lesions relevant to stroke and neurodegenerative diseases. View Full-Text
Keywords: Bcl-xL; apoptosis; oxidative stress; amyloid fibers Bcl-xL; apoptosis; oxidative stress; amyloid fibers
Show Figures

Figure 1

MDPI and ACS Style

Gonneaud, A.; Fakhir, F.-Z.; Landas, E.; Le Tallec, E.; Chartier-Garcia, E.; Almunia, C.; Chenal, A.; Forge, V.; Marquette, C. Development of Conformational Antibodies to Detect Bcl-xL’s Amyloid Aggregates in Metal-Induced Apoptotic Neuroblastoma Cells. Int. J. Mol. Sci. 2020, 21, 7625. https://doi.org/10.3390/ijms21207625

AMA Style

Gonneaud A, Fakhir F-Z, Landas E, Le Tallec E, Chartier-Garcia E, Almunia C, Chenal A, Forge V, Marquette C. Development of Conformational Antibodies to Detect Bcl-xL’s Amyloid Aggregates in Metal-Induced Apoptotic Neuroblastoma Cells. International Journal of Molecular Sciences. 2020; 21(20):7625. https://doi.org/10.3390/ijms21207625

Chicago/Turabian Style

Gonneaud, Alexis, Fatima-Zohra Fakhir, Emeline Landas, Enora Le Tallec, Elisabeth Chartier-Garcia, Christine Almunia, Alexandre Chenal, Vincent Forge, and Christel Marquette. 2020. "Development of Conformational Antibodies to Detect Bcl-xL’s Amyloid Aggregates in Metal-Induced Apoptotic Neuroblastoma Cells" International Journal of Molecular Sciences 21, no. 20: 7625. https://doi.org/10.3390/ijms21207625

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop