Tags

Type your tag names separated by a space and hit enter

Prevention of 7-ketocholesterol-induced mitochondrial damage and cell death by calmodulin inhibition.
Brain Res. 2007 Mar 16; 1137(1):11-9.BR

Abstract

Oxysterols such as 7-ketocholesterol and 25-hydroxycholesterol formed under enhanced oxidative stress in the brain are suggested to induce neuronal cell death. The present study investigated the effect of calmodulin antagonists (trifluoperazine, W-7 and calmidazolium) against the cytotoxicity of 7-ketocholesterol in relation to the mitochondria-mediated cell death process and oxidative stress. PC12 cells exposed to 7-ketocholesterol revealed nuclear damage, decrease in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species and depletion of GSH. N-Acetylcysteine, trolox, carboxy-PTIO and Mn-TBAP reduced the cytotoxic effect of 7-ketocholesterol. Calmodulin antagonists attenuated the 7-ketocholesterol-induced nuclear damage, formation of the mitochondrial permeability transition and cell viability loss in PC12 cells. The results suggest that calmodulin antagonists may prevent the 7-ketocholesterol-induced viability loss in PC12 cells by suppressing formation of the mitochondrial permeability transition, leading to the release of cytochrome c and subsequent activation of caspase-3. The effects seem to be ascribed to their depressant action on the formation of reactive oxygen species and depletion of GSH. The findings suggest that calmodulin inhibition may exhibit a protective effect against the neurotoxicity of 7-ketocholesterol.

Authors+Show Affiliations

Department of Neurology, Seoul Veterans Hospital, Seoul 134-791, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17224136

Citation

Han, Jeong Ho, et al. "Prevention of 7-ketocholesterol-induced Mitochondrial Damage and Cell Death By Calmodulin Inhibition." Brain Research, vol. 1137, no. 1, 2007, pp. 11-9.
Han JH, Kim YJ, Han ES, et al. Prevention of 7-ketocholesterol-induced mitochondrial damage and cell death by calmodulin inhibition. Brain Res. 2007;1137(1):11-9.
Han, J. H., Kim, Y. J., Han, E. S., & Lee, C. S. (2007). Prevention of 7-ketocholesterol-induced mitochondrial damage and cell death by calmodulin inhibition. Brain Research, 1137(1), 11-9.
Han JH, et al. Prevention of 7-ketocholesterol-induced Mitochondrial Damage and Cell Death By Calmodulin Inhibition. Brain Res. 2007 Mar 16;1137(1):11-9. PubMed PMID: 17224136.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prevention of 7-ketocholesterol-induced mitochondrial damage and cell death by calmodulin inhibition. AU - Han,Jeong Ho, AU - Kim,Yun Jeong, AU - Han,Eun Sook, AU - Lee,Chung Soo, Y1 - 2006/12/20/ PY - 2006/10/15/received PY - 2006/11/26/revised PY - 2006/12/14/accepted PY - 2007/1/17/pubmed PY - 2007/5/2/medline PY - 2007/1/17/entrez SP - 11 EP - 9 JF - Brain research JO - Brain Res. VL - 1137 IS - 1 N2 - Oxysterols such as 7-ketocholesterol and 25-hydroxycholesterol formed under enhanced oxidative stress in the brain are suggested to induce neuronal cell death. The present study investigated the effect of calmodulin antagonists (trifluoperazine, W-7 and calmidazolium) against the cytotoxicity of 7-ketocholesterol in relation to the mitochondria-mediated cell death process and oxidative stress. PC12 cells exposed to 7-ketocholesterol revealed nuclear damage, decrease in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species and depletion of GSH. N-Acetylcysteine, trolox, carboxy-PTIO and Mn-TBAP reduced the cytotoxic effect of 7-ketocholesterol. Calmodulin antagonists attenuated the 7-ketocholesterol-induced nuclear damage, formation of the mitochondrial permeability transition and cell viability loss in PC12 cells. The results suggest that calmodulin antagonists may prevent the 7-ketocholesterol-induced viability loss in PC12 cells by suppressing formation of the mitochondrial permeability transition, leading to the release of cytochrome c and subsequent activation of caspase-3. The effects seem to be ascribed to their depressant action on the formation of reactive oxygen species and depletion of GSH. The findings suggest that calmodulin inhibition may exhibit a protective effect against the neurotoxicity of 7-ketocholesterol. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/17224136/Prevention_of_7_ketocholesterol_induced_mitochondrial_damage_and_cell_death_by_calmodulin_inhibition_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(06)03602-X DB - PRIME DP - Unbound Medicine ER -