BDNF protects human vascular endothelial cells from TNFalpha-induced apoptosis

KATSUHIRO TAKEDA; POUNEH KERMANI; AGUSTÍN ANASTASÍA; YUSUKE OBINATA; BARBARA L HEMPSTEAD; HIDEMI KURIHARA

BIOCHEMISTRY AND CELL BIOLOGY

NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS

Año: 2013 vol. 91 p. 342 - 349

0829-8211

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  (TNF), which is known for its pro-apoptotic action in human microvascular endothelial cells (HMVECs). We demonstrate that BDNF attenuates TNF-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 TNF 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 TNF. Terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) assay showed that the PTEN inhibitor bpV(pic) rescues HMVECs from TNF-induced apoptosis. In conclusion, BDNF protects HMVECs from toxicity of TNF through the regulation of the PTEN/Akt pathway.