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Zinc-induced anti-apoptotic effects in SH-SY5Y neuroblastoma cells via the extracellular signal-regulated kinase 1/2.
Brain Res Mol Brain Res. 2005 Apr 27; 135(1-2):40-7.BR

Abstract

Zinc levels are increased in brain areas severely affected by Alzheimer's disease (AD) pathologies. Zinc has both protective and neurotoxic properties and can stimulate both phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. Several kinases related to these pathways including protein kinase B (PKB), p70 S6 kinase (p70S6K), and extracellular signal-regulated kinase 1/2 (ERK1/2) are known cell survival factors and are overactivated in neurons bearing neurofibrillary tangles (NFTs) in AD. The present study aimed to determine whether anti-apoptotic effects of zinc are mediated via these signaling pathways. Zinc was used to treat SH-SY5Y neuroblastoma cells and effects investigated in relation to PKB, p70S6K, and ERK1/2 in the absence and presence of the pro-apoptotic agent staurosporine (STS). Cell damage was evaluated by measuring levels of DNA fragmentation as well as the WST-1 assay for cell viability. Results indicated that: (1) treatment with high doses of zinc (>/=400 microM) for short time periods (</=2 h) gave rise to increased levels of DNA fragments, increased cell membrane permeability, and reduced mitochondria membrane potential; (2) treatment with 100 microM zinc for >2 h reversed an increased DNA fragmentation due to U0126 inhibition of ERK1/2; (3) increased DNA fragmentation due to STS could be protected against by 100 microM zinc; (4) the protective effects of 100 microM zinc on STS-induced DNA fragmentation could be partially reversed by U0126. These results indicate that a zinc-induced anti-apoptotic response in SH-SY5Y cells likely occurs through ERK1/2.

Authors+Show Affiliations

Division of Experimental Geriatrics, Department of Neurotec, Karolinska Institutet, Huddinge, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15857667

Citation

An, Wen-Lin, et al. "Zinc-induced Anti-apoptotic Effects in SH-SY5Y Neuroblastoma Cells Via the Extracellular Signal-regulated Kinase 1/2." Brain Research. Molecular Brain Research, vol. 135, no. 1-2, 2005, pp. 40-7.
An WL, Pei JJ, Nishimura T, et al. Zinc-induced anti-apoptotic effects in SH-SY5Y neuroblastoma cells via the extracellular signal-regulated kinase 1/2. Brain Res Mol Brain Res. 2005;135(1-2):40-7.
An, W. L., Pei, J. J., Nishimura, T., Winblad, B., & Cowburn, R. F. (2005). Zinc-induced anti-apoptotic effects in SH-SY5Y neuroblastoma cells via the extracellular signal-regulated kinase 1/2. Brain Research. Molecular Brain Research, 135(1-2), 40-7.
An WL, et al. Zinc-induced Anti-apoptotic Effects in SH-SY5Y Neuroblastoma Cells Via the Extracellular Signal-regulated Kinase 1/2. Brain Res Mol Brain Res. 2005 Apr 27;135(1-2):40-7. PubMed PMID: 15857667.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Zinc-induced anti-apoptotic effects in SH-SY5Y neuroblastoma cells via the extracellular signal-regulated kinase 1/2. AU - An,Wen-Lin, AU - Pei,Jin-Jing, AU - Nishimura,Takeshi, AU - Winblad,Bengt, AU - Cowburn,Richard F, Y1 - 2005/01/08/ PY - 2003/12/16/received PY - 2004/11/13/revised PY - 2004/11/21/accepted PY - 2005/4/29/pubmed PY - 2005/7/26/medline PY - 2005/4/29/entrez SP - 40 EP - 7 JF - Brain research. Molecular brain research JO - Brain Res Mol Brain Res VL - 135 IS - 1-2 N2 - Zinc levels are increased in brain areas severely affected by Alzheimer's disease (AD) pathologies. Zinc has both protective and neurotoxic properties and can stimulate both phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. Several kinases related to these pathways including protein kinase B (PKB), p70 S6 kinase (p70S6K), and extracellular signal-regulated kinase 1/2 (ERK1/2) are known cell survival factors and are overactivated in neurons bearing neurofibrillary tangles (NFTs) in AD. The present study aimed to determine whether anti-apoptotic effects of zinc are mediated via these signaling pathways. Zinc was used to treat SH-SY5Y neuroblastoma cells and effects investigated in relation to PKB, p70S6K, and ERK1/2 in the absence and presence of the pro-apoptotic agent staurosporine (STS). Cell damage was evaluated by measuring levels of DNA fragmentation as well as the WST-1 assay for cell viability. Results indicated that: (1) treatment with high doses of zinc (>/=400 microM) for short time periods (</=2 h) gave rise to increased levels of DNA fragments, increased cell membrane permeability, and reduced mitochondria membrane potential; (2) treatment with 100 microM zinc for >2 h reversed an increased DNA fragmentation due to U0126 inhibition of ERK1/2; (3) increased DNA fragmentation due to STS could be protected against by 100 microM zinc; (4) the protective effects of 100 microM zinc on STS-induced DNA fragmentation could be partially reversed by U0126. These results indicate that a zinc-induced anti-apoptotic response in SH-SY5Y cells likely occurs through ERK1/2. SN - 0169-328X UR - https://www.unboundmedicine.com/medline/citation/15857667/Zinc_induced_anti_apoptotic_effects_in_SH_SY5Y_neuroblastoma_cells_via_the_extracellular_signal_regulated_kinase_1/2_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0169-328X(04)00595-9 DB - PRIME DP - Unbound Medicine ER -