title: Lipopolysaccharide prevents valproic acid-induced apoptosis via activation of nuclear factor-κB and inhibition of p53 activation.
abstract: The effect of lipopolysaccharide (LPS) on valproic acid (VPA)-induced cell death was examined by using mouse RAW 264.7 macrophage cells. LPS inhibited the activation of caspase 3 and poly (ADP-ribose) polymerase and prevented VPA-induced apoptosis. LPS inhibited VPA-induced p53 activation and pifithrin-α as a p53 inhibitor as well as LPS prevented VPA-induced apoptosis. LPS abolished the increase of Bax/Bcl-2 ratio, which is a critical indicator of p53-mediated mitochondrial damage, in response to VPA. The nuclear factor (NF)-κB inhibitors, Bay 11-7082 and parthenolide, abolished the preventive action of LPS on VPA-induced apoptosis. A series of toll-like receptor ligands, Pam3CSK4, poly I:C, and CpG DNA as well as LPS prevented VPA-induced apoptosis. Taken together, LPS was suggested to prevent VPA-induced apoptosis via activation of anti-apoptotic NF-κB and inhibition of pro-apoptotic p53 activation. The detailed inhibitory mechanism of VPA-induced apoptosis by LPS is discussed.
authors.affiliation: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
authors.forename: Bilegtsaikhan
authors.initials: B
authors.lastname: Tsolmongyn
authors.forename: Naoki
authors.initials: N
authors.lastname: Koide
authors.forename: Erdenezaya
authors.initials: E
authors.lastname: Odkhuu
authors.forename: Abedul
authors.initials: A
authors.lastname: Haque
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Naiki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Komatsu
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yoshida
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokochi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015151:Immunoblotting; D055666:Lipopeptides / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology; D051217:Toll-Like Receptor 9 / Q000819:agonists; D051193:Toll-Like Receptors / Q000819:agonists; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; C494827:Bax protein, mouse; C526902:CpG ODN 2216; D055666:Lipopeptides; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009570:Nitriles; D009838:Oligodeoxyribonucleotides; C508075:Pam(3)CSK(4) peptide; D019253:Proto-Oncogene Proteins c-bcl-2; D012717:Sesquiterpenes; D013450:Sulfones; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C002669:parthenolide; D014635:Valproic Acid; D011070:Poly I-C
keywords: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2-H-tetrazolium; Apoptosis; B-cell lymphoma 2; Bax; Bcl-2; Bcl-2-associated X protein; Erk; HDAC; JNK; LPS; Lipopolysaccharide; MAPK; MTT; NF-κB; PARP; PFT-α; TLR; TUNEL; Toll-like receptor; VPA; Valproic acid; c-Jun N-terminal kinase; extracellular signal-regulated kinase; histone deacetylase; lipopolysaccharide; mitogen-activated protein kinase; nuclear factor-κB; p53; pifithrin-α; poly (ADP-ribose) polymerase; terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling; toll-like receptor; valproic acid