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Cell Immunol. 2013 Apr;282(2):100-5. doi: 10.1016/j.cellimm.2013.04.011. Epub 2013 May 4.

Lipopolysaccharide prevents valproic acid-induced apoptosis via activation of nuclear factor-κB and inhibition of p53 activation.

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Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.


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.


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

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