BDNF protects human vascular endothelial cells from TNFα-induced apoptosis

被引：32

作者：

Takeda, Katsuhiro ^{[1
]}

Kermani, Pouneh ^{[2
]}

Anastasia, Agustin ^{[2
]}

Obinata, Yusuke ^{[1
]}

Hempstead, Barbara L. ^{[2
]}

Kurihara, Hidemi ^{[1
]}

机构：

[1] Hiroshima Univ, Grad Sch Biomed Sci, Div Frontier Med Sci, Minami Ku, Hiroshima 7348553, Japan

[2] Weill Cornell Med Coll, Dept Med, Div Hematol & Med Oncol, New York, NY USA

来源：

BIOCHEMISTRY AND CELL BIOLOGY | 2013年 / 91卷 / 05期

基金：

日本学术振兴会;

关键词：

brain-derived neurotrophic factor; tumor necrosis factor-alpha; apoptosis; vascular endothelial cells; periodontal therapy; TUMOR-NECROSIS-FACTOR; NEUROTROPHIC FACTOR; PTEN; DEATH; ACTIVATION; FAMILY; EXPRESSION; SURVIVAL; NGF; PHOSPHORYLATION;

D O I：

10.1139/bcb-2013-0005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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

引用

页码：341 / 349

页数：9

共 52 条

[1] Neurotrophin signaling:: many exciting surprises! [J].

Arevalo, J. C. ;

Wu, S. H. .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2006, 63 (13) :1523-1537

[2] Biology of wound healing [J].

Aukhil, I .

PERIODONTOLOGY 2000, 2000, 22 :44-50

[3] THE TRK FAMILY OF NEUROTROPHIN RECEPTORS [J].

BARBACID, M .

JOURNAL OF NEUROBIOLOGY, 1994, 25 (11) :1386-1403

[4] New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase AKT pathway [J].

Cantley, LC ;

Neel, BG .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (08) :4240-4245

[5] Proinflammatory factors present in sera from patients with acute dengue infection induce activation and apoptosis of human microvascular endothelial cells:: Possible role of TNF-α in endothelial cell damage in dengue [J].

Cardier, JE ;

Mariño, E ;

Romano, E ;

Taylor, P ;

Liprandi, F ;

Bosch, N ;

Rothman, AL .

CYTOKINE, 2005, 30 (06) :359-365

[6] ICAM-1 and AMPK regulate cell detachment and apoptosis by N-methyl-N′-nitro-N-nitrosoguanidine, a widely spread environmental chemical, in human hormone-refractory prostate cancers [J].

Chen, Yi-Cheng ;

Lu, Pin-Hsuan ;

Hsu, Jui-Ling ;

Yu, Chia-Chun ;

Guh, Jih-Hwa .

TOXICOLOGY AND APPLIED PHARMACOLOGY, 2011, 257 (03) :412-419

[7] PTEN/MMAC1 is infrequently mutated in pT2 and pT3 carcinomas of the prostate [J].

Dong, JT ;

Sipe, TW ;

Hyytinen, ER ;

Li, CL ;

Heise, C ;

McClintock, DE ;

Grant, CD ;

Chung, LWK ;

Frierson, HF .

ONCOGENE, 1998, 17 (15) :1979-1982

[8]

Donovan MJ, 2000, DEVELOPMENT, V127, P4531

[9] FUNCTION AND EVOLUTION IN THE NGF FAMILY AND ITS RECEPTORS [J].

EBENDAL, T .

JOURNAL OF NEUROSCIENCE RESEARCH, 1992, 32 (04) :461-470

[10] Inflammation in wound repair: Molecular and cellular mechanisms [J].

Eming, Sabine A. ;

Krieg, Thomas ;

Davidson, Jeffrey M. .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2007, 127 (03) :514-525

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