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Protective role of Bcl-2 on beta-amyloid-induced cell death of differentiated PC12 cells: reduction of NF-kappaB and p38 MAP kinase activation.
Neurosci Res. 2004 May; 49(1):69-80.NR

Abstract

Activation of the apoptosis program by an increased production of beta-amyloid peptides (Abeta) has been implicated in the neuronal cell death of Alzheimer's disease (AD). Bcl-2 is a well-demonstrated anti-apoptotic protein, however, the mechanisms of anti-apoptotic action of Bcl-2 in Abeta-induced neuronal cell death are not fully understood. In the present study, we therefore have investigated the possibility that overexpression of Bcl-2 may prevent Abeta-induced cell death through inhibition of pro-apoptotic activation of p38 MAP kinase and the transcription factor NF-kappaB in nerve growth factor (NGF)-induced differentiated PC12 cells. Treatment of Abeta into differentiated PC12 cells transfected with plasmid alone resulted in increase of cell death determined by measurement of cytotoxicity and apoptosis in a dose dependent manner. Consistent with the increase of cell death, treatment of Abeta resulted in increase of p38 MAP kinase and NF-kappaB activation. However, overexpression of Bcl-2 reduced Abeta-induced apoptosis, and suppressed the activation of p38 MAP kinase and NF-kappaB. In addition, a p38 MAP kinase specific inhibitor SB 203580 attenuated Abeta-induced apoptosis. This inhibitory effect was correlated well with the inhibition of p38 MAP kniase and NF-kappaB activation. Moreover, inhibition of NF-kappaB activation by sodium salicylates reduced Abeta-induced apoptosis and activation of p38 MAP kinase, and up regulated Bcl-2 expression. These results suggest that Bcl-2 overexpression protects against Abeta-induced cell death of differentiated PC12, and its protective effect may be related to the reduction of Abeta-induced activation of p38 MAP kinase and NF-kappaB.

Authors+Show Affiliations

College of Pharmacy, Chungbuk National University 48, Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

15099705

Citation

Song, Youn Sook, et al. "Protective Role of Bcl-2 On Beta-amyloid-induced Cell Death of Differentiated PC12 Cells: Reduction of NF-kappaB and P38 MAP Kinase Activation." Neuroscience Research, vol. 49, no. 1, 2004, pp. 69-80.
Song YS, Park HJ, Kim SY, et al. Protective role of Bcl-2 on beta-amyloid-induced cell death of differentiated PC12 cells: reduction of NF-kappaB and p38 MAP kinase activation. Neurosci Res. 2004;49(1):69-80.
Song, Y. S., Park, H. J., Kim, S. Y., Lee, S. H., Yoo, H. S., Lee, H. S., Lee, M. K., Oh, K. W., Kang, S. K., Lee, S. E., & Hong, J. T. (2004). Protective role of Bcl-2 on beta-amyloid-induced cell death of differentiated PC12 cells: reduction of NF-kappaB and p38 MAP kinase activation. Neuroscience Research, 49(1), 69-80.
Song YS, et al. Protective Role of Bcl-2 On Beta-amyloid-induced Cell Death of Differentiated PC12 Cells: Reduction of NF-kappaB and P38 MAP Kinase Activation. Neurosci Res. 2004;49(1):69-80. PubMed PMID: 15099705.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective role of Bcl-2 on beta-amyloid-induced cell death of differentiated PC12 cells: reduction of NF-kappaB and p38 MAP kinase activation. AU - Song,Youn Sook, AU - Park,Hye Ji, AU - Kim,Soo Yeon, AU - Lee,Seung Ho, AU - Yoo,Hwan Soo, AU - Lee,Hee Soon, AU - Lee,Myung Koo, AU - Oh,Ki Wan, AU - Kang,Sun-Kyung, AU - Lee,Seoung Eun, AU - Hong,Jin Tae, PY - 2003/11/06/received PY - 2004/01/23/accepted PY - 2004/4/22/pubmed PY - 2004/7/21/medline PY - 2004/4/22/entrez SP - 69 EP - 80 JF - Neuroscience research JO - Neurosci. Res. VL - 49 IS - 1 N2 - Activation of the apoptosis program by an increased production of beta-amyloid peptides (Abeta) has been implicated in the neuronal cell death of Alzheimer's disease (AD). Bcl-2 is a well-demonstrated anti-apoptotic protein, however, the mechanisms of anti-apoptotic action of Bcl-2 in Abeta-induced neuronal cell death are not fully understood. In the present study, we therefore have investigated the possibility that overexpression of Bcl-2 may prevent Abeta-induced cell death through inhibition of pro-apoptotic activation of p38 MAP kinase and the transcription factor NF-kappaB in nerve growth factor (NGF)-induced differentiated PC12 cells. Treatment of Abeta into differentiated PC12 cells transfected with plasmid alone resulted in increase of cell death determined by measurement of cytotoxicity and apoptosis in a dose dependent manner. Consistent with the increase of cell death, treatment of Abeta resulted in increase of p38 MAP kinase and NF-kappaB activation. However, overexpression of Bcl-2 reduced Abeta-induced apoptosis, and suppressed the activation of p38 MAP kinase and NF-kappaB. In addition, a p38 MAP kinase specific inhibitor SB 203580 attenuated Abeta-induced apoptosis. This inhibitory effect was correlated well with the inhibition of p38 MAP kniase and NF-kappaB activation. Moreover, inhibition of NF-kappaB activation by sodium salicylates reduced Abeta-induced apoptosis and activation of p38 MAP kinase, and up regulated Bcl-2 expression. These results suggest that Bcl-2 overexpression protects against Abeta-induced cell death of differentiated PC12, and its protective effect may be related to the reduction of Abeta-induced activation of p38 MAP kinase and NF-kappaB. SN - 0168-0102 UR - https://www.unboundmedicine.com/medline/citation/15099705/Protective_role_of_Bcl_2_on_beta_amyloid_induced_cell_death_of_differentiated_PC12_cells:_reduction_of_NF_kappaB_and_p38_MAP_kinase_activation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168010204000252 DB - PRIME DP - Unbound Medicine ER -