Temporal relationships between de novo protein synthesis, calpain and caspase 3-like protease activation, and DNA fragmentation during apoptosis in septo-hippocampal cultures - PubMed (original) (raw)

Temporal relationships between de novo protein synthesis, calpain and caspase 3-like protease activation, and DNA fragmentation during apoptosis in septo-hippocampal cultures

B R Pike et al. J Neurosci Res. 1998.

Abstract

Caspase 3-like proteases are key executioners in mammalian apoptosis, and the calpain family of cysteine proteases has also been implicated as an effector of the apoptotic cascade. However, the influence of upstream events on calpain/caspase activation and the role of calpain/caspase activation on subsequent downstream events are poorly understood. This investigation examined the temporal profile of apoptosis-related events after staurosporine-induced apoptosis in mixed glial-neuronal septo-hippocampal cell cultures. Following 3 hr exposure to staurosporine (0.5 microM), calpain and caspase 3-like proteases processed alpha-spectrin to their signature proteolytic fragments prior to endonuclease-mediated DNA fragmentation (not evident until 6 hr), indicating that endonuclease activation is downstream from calpain/caspase activation. Cycloheximide, a general protein synthesis inhibitor, completely prevented processing of alpha-spectrin by calpains and caspase 3-like proteases, DNA fragmentation and cell death, indicating that de novo protein synthesis is an upstream event necessary for activation of calpains and caspase 3-like proteases. Calpain inhibitor II and the pan-caspase inhibitor Z-D-DCB each inhibited their respective protease-specific processing of alpha-spectrin and attenuated endonuclease DNA fragmentation and cell death. Thus, activation of calpains and caspase 3-like proteases is an early event in staurosporine-induced apoptosis, and synthesis of, as yet, unknown protein(s) is necessary for their activation.

PubMed Disclaimer

Cited by

Caspase inhibition protects nerve terminals from in vitro degradation.
Gylys KH, Fein JA, Cole GM. Gylys KH, et al. Neurochem Res. 2002 Jun;27(6):465-72. doi: 10.1023/a:1019840417796. Neurochem Res. 2002. PMID: 12199150
Novel Bioinformatics-Based Approach for Proteomic Biomarkers Prediction of Calpain-2 &Caspase-3 Protease Fragmentation: Application to βII-Spectrin Protein.
El-Assaad A, Dawy Z, Nemer G, Kobeissy F. El-Assaad A, et al. Sci Rep. 2017 Jan 23;7:41039. doi: 10.1038/srep41039. Sci Rep. 2017. PMID: 28112201 Free PMC article.
Protection of mature oligodendrocytes by inhibitors of caspases and calpains.
Benjamins JA, Nedelkoska L, George EB. Benjamins JA, et al. Neurochem Res. 2003 Jan;28(1):143-52. doi: 10.1023/a:1021612615554. Neurochem Res. 2003. PMID: 12587672
Mode of action of S-methyl-N, N-diethylthiocarbamate sulfoxide (DETC-MeSO) as a novel therapy for stroke in a rat model.
Mohammad-Gharibani P, Modi J, Menzie J, Genova R, Ma Z, Tao R, Prentice H, Wu JY. Mohammad-Gharibani P, et al. Mol Neurobiol. 2014 Oct;50(2):655-72. doi: 10.1007/s12035-014-8658-0. Epub 2014 Feb 28. Mol Neurobiol. 2014. PMID: 24573692
Biomarkers of proteolytic damage following traumatic brain injury.
Pineda JA, Wang KK, Hayes RL. Pineda JA, et al. Brain Pathol. 2004 Apr;14(2):202-9. doi: 10.1111/j.1750-3639.2004.tb00054.x. Brain Pathol. 2004. PMID: 15193033 Free PMC article. Review.

Temporal relationships between de novo protein synthesis, calpain and caspase 3-like protease activation, and DNA fragmentation during apoptosis in septo-hippocampal cultures - PubMed (original) (raw)