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17β-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells via the PI3K/Akt Pathway.
Med Sci Monit. 2016 Nov 12; 22:4312-4322.MS

Abstract

BACKGROUND

Tumor necrosis factor-α (TNF-α) has been widely known to induce degeneration of nucleus pulposus cells (NPCs). 17β-estradiol (17β-E2) has been broadly proven for its function of suppressing cell apoptosis. The aim of this study is to explore whether 17β-E2 protects apoptosis of human NPCs induced by TNF-α via the PI3K/AKT pathway. MATERIAL AND

METHODS

NPCs were divided into four groups: control, TNF-α (100 ng/mL), TNF-α (100 ng/mL) with pretreated 17β-E2 (10 um/L), TNF-α (100 ng/mL) with pretreated 17β-E2 (10 um/L) and MK2206 (10 um/L, inhibitor of the PI3K/AKT pathway). Flow cytometry was used to measure the apoptotic incidence. Inverted phase-contrast microscopy was used to accomplish the morphological observation for apoptosis of treated cells. Additionally, Cell Counting Kit 8 (CCK-8) assay was used to detected cell proliferation. Western blot and quantitative real-time PCR (qRT-PCR) were applied to explore the expression of pro-caspase-3, caspase-3/p17, cleaved PARP, PARP, Akt, and phospho-Akt (p-Akt).

RESULTS

First, inverted phase-contrast microscopy, CCK-8, and flow cytometry showed that TNF-α induced marked apoptosis, which was abolished by 17β-E2. Furthermore, Western blot and qRT-PCR showed that 17β-E2 protects TNF-α which can induced apoptosis by upregulating p-Akt, whereas Akt was essentially constant. Our data revealed that p-Akt expression peaked at 24 hours in a time-dependent manner (0-48 hours) after treating with TNF-α; and the p-Akt expression generally increased in a time-dependent manner (0-48 hours) after treating with TNF-α and 17β-E2.

CONCLUSIONS

17β-E2 is shown to protect NPCs against TNF-α induced apoptosis by upregulating p-Akt in the PI3K/AKT pathway. 17β-E2 generally increases expression of p-Akt.

Authors+Show Affiliations

Department of Spinal Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).Department of Spinal Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).Department of Spinal Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).Department of Spinal Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).Department of Spinal Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).Department of Spinal Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27847386

Citation

Wang, Tao, et al. "17β-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells Via the PI3K/Akt Pathway." Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, vol. 22, 2016, pp. 4312-4322.
Wang T, Yang SD, Liu S, et al. 17β-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells via the PI3K/Akt Pathway. Med Sci Monit. 2016;22:4312-4322.
Wang, T., Yang, S. D., Liu, S., Wang, H., Liu, H., & Ding, W. Y. (2016). 17β-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells via the PI3K/Akt Pathway. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, 22, 4312-4322.
Wang T, et al. 17β-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells Via the PI3K/Akt Pathway. Med Sci Monit. 2016 Nov 12;22:4312-4322. PubMed PMID: 27847386.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 17β-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells via the PI3K/Akt Pathway. AU - Wang,Tao, AU - Yang,Si-Dong, AU - Liu,Sen, AU - Wang,Hui, AU - Liu,Huan, AU - Ding,Wen Yuan, Y1 - 2016/11/12/ PY - 2016/11/17/entrez PY - 2016/11/17/pubmed PY - 2017/4/12/medline KW - Accessory nerve KW - Estriol KW - Tumor Necrosis Factors SP - 4312 EP - 4322 JF - Medical science monitor : international medical journal of experimental and clinical research JO - Med Sci Monit VL - 22 N2 - BACKGROUND Tumor necrosis factor-α (TNF-α) has been widely known to induce degeneration of nucleus pulposus cells (NPCs). 17β-estradiol (17β-E2) has been broadly proven for its function of suppressing cell apoptosis. The aim of this study is to explore whether 17β-E2 protects apoptosis of human NPCs induced by TNF-α via the PI3K/AKT pathway. MATERIAL AND METHODS NPCs were divided into four groups: control, TNF-α (100 ng/mL), TNF-α (100 ng/mL) with pretreated 17β-E2 (10 um/L), TNF-α (100 ng/mL) with pretreated 17β-E2 (10 um/L) and MK2206 (10 um/L, inhibitor of the PI3K/AKT pathway). Flow cytometry was used to measure the apoptotic incidence. Inverted phase-contrast microscopy was used to accomplish the morphological observation for apoptosis of treated cells. Additionally, Cell Counting Kit 8 (CCK-8) assay was used to detected cell proliferation. Western blot and quantitative real-time PCR (qRT-PCR) were applied to explore the expression of pro-caspase-3, caspase-3/p17, cleaved PARP, PARP, Akt, and phospho-Akt (p-Akt). RESULTS First, inverted phase-contrast microscopy, CCK-8, and flow cytometry showed that TNF-α induced marked apoptosis, which was abolished by 17β-E2. Furthermore, Western blot and qRT-PCR showed that 17β-E2 protects TNF-α which can induced apoptosis by upregulating p-Akt, whereas Akt was essentially constant. Our data revealed that p-Akt expression peaked at 24 hours in a time-dependent manner (0-48 hours) after treating with TNF-α; and the p-Akt expression generally increased in a time-dependent manner (0-48 hours) after treating with TNF-α and 17β-E2. CONCLUSIONS 17β-E2 is shown to protect NPCs against TNF-α induced apoptosis by upregulating p-Akt in the PI3K/AKT pathway. 17β-E2 generally increases expression of p-Akt. SN - 1643-3750 UR - https://www.unboundmedicine.com/medline/citation/27847386/17β_Estradiol_Inhibites_Tumor_Necrosis_Factor_α_Induced_Apoptosis_of_Human_Nucleus_Pulposus_Cells_via_the_PI3K/Akt_Pathway_ L2 - https://www.medscimonit.com/download/index/idArt/900310 DB - PRIME DP - Unbound Medicine ER -