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Inhibitor of double stranded RNA-dependent protein kinase protects against cell damage induced by ER stress.
Neurosci Lett. 2006 Dec 06; 409(3):192-5.NL

Abstract

Endoplasmic reticulum (ER)-stress is known to induce neuronal cell death and to play roles in neurodegenerative diseases. Phosphorylation of double stranded RNA-dependent protein kinase (PKR) has been demonstrated in brain tissues in patients with Alzheimer's, Parkinson's, and Huntington's diseases. Here, we examined the effect of a PKR inhibitor (an imidazolo-oxindole derivative that acts as an ATP-binding site-directed inhibitor of PKR) on the neuronal cell death induced by ER-stress in cultured human neuroblastoma cells (SH-SY5Y). Cell damage was induced by tunicamycin (an ER-stress inducer), and cell viability was measured by Hoechst 33342 and YO-PRO-1 double staining and by the resazurin-reduction test (to evaluate metabolic activity). Treatment with tunicamycin at 2 microg/ml for 24 h induced apoptotic cell death accompanied by nuclear condensation and/or fragmentation, and these cells were positive for YO-PRO-1 (early-phase apoptosis and necrosis indicator). Treatment with the PKR inhibitor at 0.1 or 0.3 microM led to a decrease in the number of apoptotic cells induced by tunicamycin. In the resazurin-reduction test, the PKR inhibitor (at 0.1 and 0.3 microM) concentration-dependently inhibited the tunicamycin-induced decrease in metabolic activity. On the other hand, treatment with the PKR inhibitor alone (at 0.3 microM) had no effect on cell morphology or viability (versus in normal control cells). These results indicate that inhibition of PKR activation may be neuroprotective against ER stress-induced cell damage.

Authors+Show Affiliations

Department of Biofunctional Molecules, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17055645

Citation

Shimazawa, Masamitsu, and Hideaki Hara. "Inhibitor of Double Stranded RNA-dependent Protein Kinase Protects Against Cell Damage Induced By ER Stress." Neuroscience Letters, vol. 409, no. 3, 2006, pp. 192-5.
Shimazawa M, Hara H. Inhibitor of double stranded RNA-dependent protein kinase protects against cell damage induced by ER stress. Neurosci Lett. 2006;409(3):192-5.
Shimazawa, M., & Hara, H. (2006). Inhibitor of double stranded RNA-dependent protein kinase protects against cell damage induced by ER stress. Neuroscience Letters, 409(3), 192-5.
Shimazawa M, Hara H. Inhibitor of Double Stranded RNA-dependent Protein Kinase Protects Against Cell Damage Induced By ER Stress. Neurosci Lett. 2006 Dec 6;409(3):192-5. PubMed PMID: 17055645.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibitor of double stranded RNA-dependent protein kinase protects against cell damage induced by ER stress. AU - Shimazawa,Masamitsu, AU - Hara,Hideaki, Y1 - 2006/10/20/ PY - 2006/08/22/received PY - 2006/09/15/revised PY - 2006/09/21/accepted PY - 2006/10/24/pubmed PY - 2007/1/5/medline PY - 2006/10/24/entrez SP - 192 EP - 5 JF - Neuroscience letters JO - Neurosci Lett VL - 409 IS - 3 N2 - Endoplasmic reticulum (ER)-stress is known to induce neuronal cell death and to play roles in neurodegenerative diseases. Phosphorylation of double stranded RNA-dependent protein kinase (PKR) has been demonstrated in brain tissues in patients with Alzheimer's, Parkinson's, and Huntington's diseases. Here, we examined the effect of a PKR inhibitor (an imidazolo-oxindole derivative that acts as an ATP-binding site-directed inhibitor of PKR) on the neuronal cell death induced by ER-stress in cultured human neuroblastoma cells (SH-SY5Y). Cell damage was induced by tunicamycin (an ER-stress inducer), and cell viability was measured by Hoechst 33342 and YO-PRO-1 double staining and by the resazurin-reduction test (to evaluate metabolic activity). Treatment with tunicamycin at 2 microg/ml for 24 h induced apoptotic cell death accompanied by nuclear condensation and/or fragmentation, and these cells were positive for YO-PRO-1 (early-phase apoptosis and necrosis indicator). Treatment with the PKR inhibitor at 0.1 or 0.3 microM led to a decrease in the number of apoptotic cells induced by tunicamycin. In the resazurin-reduction test, the PKR inhibitor (at 0.1 and 0.3 microM) concentration-dependently inhibited the tunicamycin-induced decrease in metabolic activity. On the other hand, treatment with the PKR inhibitor alone (at 0.3 microM) had no effect on cell morphology or viability (versus in normal control cells). These results indicate that inhibition of PKR activation may be neuroprotective against ER stress-induced cell damage. SN - 0304-3940 UR - https://www.unboundmedicine.com/medline/citation/17055645/Inhibitor_of_double_stranded_RNA_dependent_protein_kinase_protects_against_cell_damage_induced_by_ER_stress_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(06)01015-9 DB - PRIME DP - Unbound Medicine ER -