title: BDNF protects human vascular endothelial cells from TNFα-induced apoptosis.
abstract: Brain-derived neurotrophic factor (BDNF) enhances periodontal tissue regeneration. Tissue regeneration is characterized by inflammation that directs the quality of tissue repair. In this study, we investigated the anti-apoptotic effect of BDNF against the toxicity of tumor necrosis factor α (TNFα), which is known for its pro-apoptotic action in human microvascular endothelial cells (HMVECs). We demonstrate that BDNF attenuates TNFα-increased Annexin V-positive cells, lactic dehydrogenase (LDH) release, and intercellular adhesion molecule 1 (ICAM-1) mRNA and cleaved caspase-3 expression. In addition, biochemical analyses indicate that TNFα increases phosphatase and tensin homolog (PTEN) expression; however, it decreases phosphorylated PTEN. BDNF did not affect PTEN expression, but it did increase the phosphorylation of PTEN. BDNF-induced Akt phosphorylation was inhibited by TNFα. Terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) assay showed that the PTEN inhibitor bpV(pic) rescues HMVECs from TNFα-induced apoptosis. In conclusion, BDNF protects HMVECs from toxicity of TNFα through the regulation of the PTEN/Akt pathway.
authors.affiliation: a Division of Frontier Medical Science, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Takeda
authors.forename: Pouneh
authors.initials: P
authors.lastname: Kermani
authors.forename: Agustin
authors.initials: A
authors.lastname: Anastasia
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Obinata
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Hempstead
authors.forename: Hidemi
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D053148:Caspase 3 / Q000096:biosynthesis / Q000378:metabolism; D002460:Cell Line; D019610:Cytoprotection; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D012038:Regeneration / Q000502:physiology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D017304:Annexin A5; D019208:Brain-Derived Neurotrophic Factor; D009942:Organometallic Compounds; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C119540:oxodiperoxo(pyridine-2-carboxylate)vanadate(V); D018799:Intercellular Adhesion Molecule-1; C579455:BDNF protein, human; D007770:L-Lactate Dehydrogenase; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D053148:Caspase 3