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6-Hydroxydopamine (6-OHDA) induces Drp1-dependent mitochondrial fragmentation in SH-SY5Y cells.
Free Radic Biol Med. 2008 Jun 01; 44(11):1960-9.FR

Abstract

Mitochondrial alterations have been associated with the cytotoxic effect of 6-hydroxydopamine (6-OHDA), a widely used neurotoxin to study Parkinson's disease. Herein we studied the potential effects of 6-OHDA on mitochondrial morphology in SH-SY5Y neuroblastoma cells. By immunofluorescence and time-lapse fluorescence microscopy we demonstrated that 6-OHDA induced profound mitochondrial fragmentation in SH-SY5Y cells, an event that was similar to mitochondrial fission induced by overexpression of Fis1p, a membrane adaptor for the dynamin-related protein 1 (DLP1/Drp1). 6-OHDA failed to induce any changes in peroxisome morphology. Biochemical experiments revealed that 6-OHDA-induced mitochondrial fragmentation is an early event preceding the collapse of the mitochondrial membrane potential and cytochrome c release in SH-SY5Y cells. Silencing of DLP1/Drp1, which is involved in mitochondrial and peroxisomal fission, prevented 6-OHDA-induced fragmentation of mitochondria. Furthermore, in cells silenced for Drp1, 6-OHDA-induced cell death was reduced, indicating that a block in mitochondrial fission protects SH-SY5Y cells against 6-OHDA toxicity. Experiments in mouse embryonic fibroblasts deficient in Bax or p53 revealed that both proteins are not essential for 6-OHDA-induced mitochondrial fragmentation. Our data demonstrate for the first time an involvement of mitochondrial fragmentation and Drp1 function in 6-OHDA-induced apoptosis.

Authors+Show Affiliations

Grupo de Neurofarmacología, Department Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha-Centro Regional de Investigaciones Biomédicas, Albacete, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18395527

Citation

Gomez-Lazaro, Maria, et al. "6-Hydroxydopamine (6-OHDA) Induces Drp1-dependent Mitochondrial Fragmentation in SH-SY5Y Cells." Free Radical Biology & Medicine, vol. 44, no. 11, 2008, pp. 1960-9.
Gomez-Lazaro M, Bonekamp NA, Galindo MF, et al. 6-Hydroxydopamine (6-OHDA) induces Drp1-dependent mitochondrial fragmentation in SH-SY5Y cells. Free Radic Biol Med. 2008;44(11):1960-9.
Gomez-Lazaro, M., Bonekamp, N. A., Galindo, M. F., Jordán, J., & Schrader, M. (2008). 6-Hydroxydopamine (6-OHDA) induces Drp1-dependent mitochondrial fragmentation in SH-SY5Y cells. Free Radical Biology & Medicine, 44(11), 1960-9. https://doi.org/10.1016/j.freeradbiomed.2008.03.009
Gomez-Lazaro M, et al. 6-Hydroxydopamine (6-OHDA) Induces Drp1-dependent Mitochondrial Fragmentation in SH-SY5Y Cells. Free Radic Biol Med. 2008 Jun 1;44(11):1960-9. PubMed PMID: 18395527.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 6-Hydroxydopamine (6-OHDA) induces Drp1-dependent mitochondrial fragmentation in SH-SY5Y cells. AU - Gomez-Lazaro,Maria, AU - Bonekamp,Nina A, AU - Galindo,Maria F, AU - Jordán,Joaquin, AU - Schrader,Michael, Y1 - 2008/03/20/ PY - 2007/10/12/received PY - 2008/02/21/revised PY - 2008/03/11/accepted PY - 2008/4/9/pubmed PY - 2008/7/30/medline PY - 2008/4/9/entrez SP - 1960 EP - 9 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 44 IS - 11 N2 - Mitochondrial alterations have been associated with the cytotoxic effect of 6-hydroxydopamine (6-OHDA), a widely used neurotoxin to study Parkinson's disease. Herein we studied the potential effects of 6-OHDA on mitochondrial morphology in SH-SY5Y neuroblastoma cells. By immunofluorescence and time-lapse fluorescence microscopy we demonstrated that 6-OHDA induced profound mitochondrial fragmentation in SH-SY5Y cells, an event that was similar to mitochondrial fission induced by overexpression of Fis1p, a membrane adaptor for the dynamin-related protein 1 (DLP1/Drp1). 6-OHDA failed to induce any changes in peroxisome morphology. Biochemical experiments revealed that 6-OHDA-induced mitochondrial fragmentation is an early event preceding the collapse of the mitochondrial membrane potential and cytochrome c release in SH-SY5Y cells. Silencing of DLP1/Drp1, which is involved in mitochondrial and peroxisomal fission, prevented 6-OHDA-induced fragmentation of mitochondria. Furthermore, in cells silenced for Drp1, 6-OHDA-induced cell death was reduced, indicating that a block in mitochondrial fission protects SH-SY5Y cells against 6-OHDA toxicity. Experiments in mouse embryonic fibroblasts deficient in Bax or p53 revealed that both proteins are not essential for 6-OHDA-induced mitochondrial fragmentation. Our data demonstrate for the first time an involvement of mitochondrial fragmentation and Drp1 function in 6-OHDA-induced apoptosis. SN - 0891-5849 UR - https://www.unboundmedicine.com/medline/citation/18395527/6_Hydroxydopamine__6_OHDA__induces_Drp1_dependent_mitochondrial_fragmentation_in_SH_SY5Y_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(08)00152-4 DB - PRIME DP - Unbound Medicine ER -