Targeted Gene Inactivation of Calpain-1 Suppresses Cortical Degeneration Due to Traumatic Brain Injury and Neuronal Apoptosis Induced by Oxidative Stress*
| Autor: | Shafi M. Kuchay, Ira M. Herman, Premanand Sundivakkam, Stacey E. Seidl, Chinnaswamy Tiruppathi, Kaori H. Yamada, Imran Chishti, Dorothy A. Kozlowski, Steven Lance, Adam J. Wieschhaus, Athar H. Chishti |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Male
Programmed cell death Traumatic brain injury Neural degeneration Apoptosis Mitochondrion medicine.disease_cause Biochemistry Mice medicine Animals RNA Small Interfering Molecular Biology Uncategorized Mice Knockout Neurons biology Calpain Caspase 3 Apoptosis Inducing Factor Anatomy Cell Biology medicine.disease Cell biology Mice Inbred C57BL Disease Models Animal Oxidative Stress Brain Injuries Mitochondrial Membranes Nerve Degeneration biology.protein Apoptosis-inducing factor Calcium Female Oxidative stress |
| DOI: | 10.25417/uic.21235707.v1 |
| Popis: | Calpains are calcium-regulated cysteine proteases that have been implicated in the regulation of cell death pathways. Here, we used our calpain-1 null mouse model to evaluate the function of calpain-1 in neural degeneration following a rodent model of traumatic brain injury. In vivo, calpain-1 null mice show significantly less neural degeneration and apoptosis and a smaller contusion 3 days post-injury than wild type littermates. Protection from traumatic brain injury corroborated with the resistance of calpain-1 neurons to apoptosis induced by oxidative stress. Biochemical analysis revealed that caspase-3 activation, extracellular calcium entry, mitochondrial membrane permeability, and release of apoptosis-inducing factor from mitochondria are partially blocked in the calpain-1 null neurons. These findings suggest that the calpain-1 knock-out mice may serve as a useful model system for neuronal protection and apoptosis in traumatic brain injury and other neurodegenerative disorders in which oxidative stress plays a role. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|