PMID- 24032685 OWN - NLM STAT- MEDLINE DCOM- 20140403 LR - 20181202 IS - 1208-6002 (Electronic) IS - 0829-8211 (Linking) VI - 91 IP - 5 DP - 2013 Oct TI - BDNF protects human vascular endothelial cells from TNFalpha-induced apoptosis. PG - 341-9 LID - 10.1139/bcb-2013-0005 [doi] AB - 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 alpha (TNFalpha), which is known for its pro-apoptotic action in human microvascular endothelial cells (HMVECs). We demonstrate that BDNF attenuates TNFalpha-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 TNFalpha 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 TNFalpha. Terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) assay showed that the PTEN inhibitor bpV(pic) rescues HMVECs from TNFalpha-induced apoptosis. In conclusion, BDNF protects HMVECs from toxicity of TNFalpha through the regulation of the PTEN/Akt pathway. FAU - Takeda, Katsuhiro AU - Takeda K AD - a Division of Frontier Medical Science, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan. FAU - Kermani, Pouneh AU - Kermani P FAU - Anastasia, Agustin AU - Anastasia A FAU - Obinata, Yusuke AU - Obinata Y FAU - Hempstead, Barbara L AU - Hempstead BL FAU - Kurihara, Hidemi AU - Kurihara H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130610 PL - Canada TA - Biochem Cell Biol JT - Biochemistry and cell biology = Biochimie et biologie cellulaire JID - 8606068 RN - 0 (Annexin A5) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Organometallic Compounds) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (oxodiperoxo(pyridine-2-carboxylate)vanadate(V)) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 7171WSG8A2 (BDNF protein, human) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (PTEN protein, human) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Annexin A5/metabolism MH - Apoptosis/*drug effects MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Caspase 3/biosynthesis/metabolism MH - Cell Line MH - *Cytoprotection MH - Endothelial Cells/*drug effects MH - Humans MH - Inflammation/metabolism MH - Intercellular Adhesion Molecule-1/genetics MH - L-Lactate Dehydrogenase/metabolism MH - Organometallic Compounds/pharmacology MH - PTEN Phosphohydrolase/antagonists & inhibitors/biosynthesis/*metabolism MH - Phosphorylation MH - Proto-Oncogene Proteins c-akt/*metabolism MH - RNA, Messenger/biosynthesis MH - Regeneration/physiology MH - Signal Transduction MH - Tumor Necrosis Factor-alpha/*antagonists & inhibitors EDAT- 2013/09/17 06:00 MHDA- 2014/04/04 06:00 CRDT- 2013/09/17 06:00 PHST- 2013/09/17 06:00 [entrez] PHST- 2013/09/17 06:00 [pubmed] PHST- 2014/04/04 06:00 [medline] AID - 10.1139/bcb-2013-0005 [doi] PST - ppublish SO - Biochem Cell Biol. 2013 Oct;91(5):341-9. doi: 10.1139/bcb-2013-0005. Epub 2013 Jun 10.