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Published on: December 9, 2022
Calbindin-D28K Prevents Staurosporin-induced Bax Cleavage and Membrane Permeabilization
1School of Biological Sciences and Technology, College of Natural Sciences, College of Medicine, Chonnam National University, Gwangju 500-757, Korea. ; Department of Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749, Korea.
Abstract:
Calbindin-D28K has been implicated in the regulation of neuronal cell death. Previously, we demonstrated that calbindin-D28K prevents staurosporine (STS)-induced caspase activation and subsequent apoptosis in a neuronal cell line. However, the role of calbindin-D28K in STS-induced activation of calpain and necrotic cell death was not identified. Staurosporine induced the elevation of intracellular calcium after 1 hr of treatment. Overexpression of calbindin-D28K and presence of a calcium chelator, BAPTA, prevented the increase of calcium in STS-treated cells. Cleavage of Bax by calpain was prevented by the overexpressed calbindin-D28K. Permeabilization of the plasma membrane, a factor in necrosis, as well as apoptotic change of the nucleolus induced by STS, was prevented by calbindin-D28K. Thus, our study suggests that calbindin-D28K may exert its protective functions by preventing calpain activation in necrotic cell death, in addition to its effect on the caspase-apoptosis pathway.
Insights
Calbindin-D28K protein protects neurons from cell death by inhibiting both apoptosis and necrosis. It prevents calcium increase and calpain activation, crucial steps in these damaging pathways.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Calbindin-D28K is known to regulate neuronal cell death.
- Previous studies showed its role in preventing apoptosis via caspase activation.
- Its role in staurosporine-induced calpain activation and necrosis was unclear.
Purpose of the Study:
- To investigate the role of Calbindin-D28K in staurosporine-induced calpain activation and necrotic cell death.
- To determine if Calbindin-D28K affects intracellular calcium levels and calpain activity.
Main Methods:
- Neuronal cell line treated with staurosporine (STS).
- Overexpression of Calbindin-D28K and use of calcium chelator BAPTA.
- Measurement of intracellular calcium levels.
- Analysis of Bax cleavage by calpain.
- Assessment of plasma membrane permeabilization and nucleolus morphology.
Main Results:
- Staurosporine increased intracellular calcium within 1 hour.
- Calbindin-D28K overexpression and BAPTA prevented this calcium increase.
- Calbindin-D28K inhibited staurosporine-induced cleavage of Bax by calpain.
- Calbindin-D28K prevented plasma membrane permeabilization and nucleolar changes induced by staurosporine.
Conclusions:
- Calbindin-D28K protects neurons from necrotic cell death by preventing calpain activation.
- These findings expand the known protective functions of Calbindin-D28K beyond the caspase-apoptosis pathway.
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