title: NF-κB p65/p52 plays a role in GDNF up-regulating Bcl-2 and Bcl-w expression in 6-OHDA-induced apoptosis of MN9D cell.
abstract: Glial-cell-line-derived neurotrophic factor (GDNF) has been shown to protect dopaminergic (DA) neurons against 6-hydroxydopamine (6-OHDA) toxicity. The mechanism underlying the antiapoptosis role of GDNF still needs further studies. We previously observed that nuclear factor-kappaB (NF-κB) signaling pathway, i.e. p65/p52, mediated the antiapoptosis role of GDNF in MN9D cells. Here, the DA cell line MN9D was used to explore the mechanisms underlying NF-κB p65/p52-mediated protection role of GDNF in DA neurons. The results showed that GDNF pretreatment blocked the apoptotic effects induced by 6-OHDA, with the upregulation of the antiapoptotic protein, Bcl-2 and Bcl-w, as well as the downregulation of the proapoptotic proteins, Bax and Bad. Furthermore, when sip100 plasmids were transfected into MN9D cells to inhibit the expression of p100, which was the precursor of p52, the effects of GDNF on upregulating Bcl-2 and Bcl-w were attenuated. These results indicated that GDNF could protect MN9D cells from apoptosis induced by 6-OHDA via upregulating Bcl-2 and Bcl-w expressions and downregulating Bax and Bad expressions. Moreover, NF-κB p65/p52 signaling mediated the effects of GDNF on Bcl-2 and Bcl-w expressions.
authors.affiliation: 1Department of Neurobiology and Anatomy.
authors.forename: Jun Ping
authors.initials: JP
authors.lastname: Cao
authors.forename: Hong Yan
authors.initials: HY
authors.lastname: Niu
authors.forename: Hong Jun
authors.initials: HJ
authors.lastname: Wang
authors.forename: Xian Gui
authors.initials: XG
authors.lastname: Huang
authors.forename: Dian Shuai
authors.initials: DS
authors.lastname: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D019254:Genes, bcl-2 / Q000235:genetics*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics*; D006892:Hydroxydopamines / Q000494:pharmacology*; D008636:Mesencephalon / Q000166:cytology; D051379:Mice; D052003:NF-kappa B p52 Subunit / Q000235:genetics* / Q000502:physiology; D010957:Plasmids / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D051996:Transcription Factor RelA / Q000235:genetics* / Q000502:physiology; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C101155:Bcl2l2 protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006892:Hydroxydopamines; D052003:NF-kappa B p52 Subunit; D011506:Proteins; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein