内质网应激通路在棕榈酸诱导的人牙周膜干细胞凋亡中的作用

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摘要目的探讨内质网应激通路在棕榈酸（PA）诱导的人牙周膜干细胞（hPDLSCs）凋亡中的作用机制。方法将培养的hPDLSCs随机分为对照组（不含PA的培养基），PA低、中、高浓度（0.1、0.2、0.4 mmol/L）组以探究PA抑制hPDLSCs增殖的作用机制；将培养的hPDLSCs分为对照组（不含PA的培养基）、PA组（0.4 mmol/L）、PA（0.4 mmol/L）+4-PBA（5 μmol/L）组以探究4-PBA对PA所致hPDLSCs凋亡的影响。培养24 h后MTT法检测各组hPDLSCs增殖率，Annexin V-FITC /PI探针观察各组hPDLSCs细胞凋亡情况，免疫印迹法检测内质网应激凋亡相关蛋白表达。结果 PA低、中、高浓度组hPDLSCs增殖率明显低于对照组（P ＜ 0.05）；PA高浓度组细胞核红色荧光和细胞膜绿色荧光较对照组明显增加；PA高浓度组IRE1phos、PERKphos、ATF4、ATF6、CHOP表达明显高于对照组（P ＜ 0.05）；PA中、高浓度组Cleaved caspase-3表达明显高于对照组（P ＜ 0.05）；与PA低、中浓度组比较，PA高浓度组IRE1phos、PERKphos、ATF6、ATF4、CHOP、Cleaved caspase-3蛋白表达均明显升高（P ＜ 0.05）；与PA组比较，PA+4-PBA组PERKphos、CHOP及Cleaved caspase-3表达明显下调（P ＜ 0.05）。结论 PA可能通过调控内质网应激凋亡通路蛋白表达，促进hPDLSCs凋亡。

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	刘涛1
	2 李晶2 鲍翠玉2

关键词 ：内质网应激, 人牙周膜干细胞, 棕榈酸, 细胞增殖, 凋亡

Abstract：Objective To investigate the mechanism of endoplasmic reticulum stress pathway in the apoptosis of human periodontal ligament stem cells (hPDLSCs) induced by palmitic acid (PA). Methods The cultured hPDLSCs were randomly divided into control group (medium without PA), low, medium, and high concentrations of PA (0.1, 0.2, and 0.4 mmol/L) groups to explore the mechanism of PA inhibiting hPDLSCs proliferation; the cultured hPDLSCs were divided into control group (medium without PA), PA group (0.4 mmol/L) and PA (0.4 mmol/L) +4-PBA group (5 μmol/L) to explore the effect of 4-PBA on the apoptosis of hPDLSCs induced by PA. After 24 h of culture, the proliferation rate of hPDLSCs in each group was detected by MTT assay, the apoptosis of hPDLSCs in each group was observed by Annexin V-FITC/PI probe, and the expression of endoplasmic reticulum stress apoptosic-related proteins was detected by Western blot. Results The proliferation rate of hPDLSCs in low, medium, and high PA groups was significantly lower than that in control group (P ＜ 0.05). The nuclear red fluorescence and cell membrane green fluorescence of PA high concentration group were increased significantly compared with cortrol group. The expressions of IRE1phos, PERKphos, ATF4, ATF6, and CHOP in PA high concentration group were significantly higher than those in control group (P ＜ 0.05). Cleaved caspase-3 expression in PA medium and high concentration groups was significantly higher than that in control group (P ＜ 0.05). Compared with PA low and medium concentrations groups, IRE1phos, PERKphos, ATF6, ATF4, CHOP, and Cleaved caspase-3 protein expressions in PA high concentration group were significantly increased (P < 0.05). Compared with PA group, PERKphos, CHOP, and Cleaved caspase-3 expressions were significantly down-regulated in PA+4-PBA group (P ＜ 0.05). Conclusion PA may promote the apoptosis of hPDLSCs by regulating the protein expression of endoplasmic reticulum stress apoptosis pathway.

Key words： Endoplasmic reticulum stress Human periodontal membrane stem cells Palmitic acid Cell proliferation Apoptosis

基金资助:国家自然科学基金资助项目（51703055）；
湖北省自然科学基金项目（2017CFB699）；
湖北省咸宁市市级科技计划项目（咸科技发〔2018〕18号-49）；
湖北省咸宁市科技创新专项项目（咸财函〔2019〕146号-2）；
湖北科技学院校内科研发展基金项目校内培育科研项目资助（2021-22X16）；
湖北科技学院五官医学院专项科研基金项目（2020WG14）。

通讯作者: 鲍翠玉（1969-），女，博士，教授，硕士生导师；研究方向：糖尿病药理学。

作者简介: 刘涛（1981-），男，硕士；研究方向：糖尿病牙周病药理学。

引用本文:

刘涛1,2 李晶2 鲍翠玉2. 内质网应激通路在棕榈酸诱导的人牙周膜干细胞凋亡中的作用[J]. 中国医药导报, 2022, 19(4): 4-8.
LIU Tao1,2 LI Jing2 BAO Cuiyu2. Role of endoplasmic reticulum stress pathway in palmitic acid-induced apoptosis of human periodontal membrane stem cells#br#. 中国医药导报, 2022, 19(4): 4-8.

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[1] Bascones-Martinez A，Gonzalez-Febles J，Sanz-Esporrin J. Diabetes and periodontal disease. Review of the literature [J]. Am J Dent，2014，27（2）：63-67.
[2] Mesia R，Gholami F，Huang H，et al. Systemic inflammatory responses in patients with type 2 diabetes with chronic periodontitis [J]. BMJ Open Diabetes Res Care，2016，4（1）：e260.
[3] Bahammam MA，Attia MS. Effects of Systemic Simvastatin on the Concentrations of Visfatin，Tumor Necrosis Factor-alpha，and Interleukin-6 in Gingival Crevicular Fluid in Patients with Type 2 Diabetes and Chronic Periodontitis [J]. J Immunol Res，2018，2018：8481735.
[4] Graves DT，Ding Z，Yang Y. The impact of diabetes on periodontal diseases [J]. Periodontol 2000，2020，82（1）：214-224.
[5] 阳琰，高琳，郝涛，等.糖尿病合并牙周病与糖脂代谢的关系[J].重庆医学，2011，40（5）：443-444.
[6] 陈丹，吴基良，李晶.内质网应激信号通路在高脂诱导的心肌细胞损伤中的作用[J].中国药理学通报，2017，33（7）：966-971.
[7] Nagata M，Iwasaki K，Akazawa K，et al. Conditioned Medium from Periodontal Ligament Stem Cells Enhances Periodontal Regeneration [J]. Tissue Eng Part A，2017，23（9/10）：367-377.
[8] Yan B，Zhang H，Dai T，et al. Necrostatin-1 promotes ectopic periodontal tissue like structure regeneration in LPS-treated PDLSCs [J]. PLoS One，2018，13（11）：e207760.
[9] Yan W，Cao Y，Yang H，et al. CB1 enhanced the osteo/dentinogenic differentiation ability of periodontal ligament stem cells via p38 MAPK and JNK in an inflammatory environment [J]. Cell Prolif，2019，52（6）：e12691.
[10] 周洋.微小RNA-218-5p靶向TLR2基因对LPS所致人牙周膜干细胞炎症反应的影响[J].口腔医学研究，2020， 36（12）：1108-1112.
[11] Yang L，Guan G，Lei L，et al. Palmitic acid induces human osteoblast-like Saos-2 cell apoptosis via endoplasmic reticulum stress and autophagy [J]. Cell Stress Chaperones，2018，23（6）：1283-1294.
[12] Takeuchi T，Masuno K，Umeda M，et al. Palmitate induces apoptosis and inhibits osteogenic differentiation of human periodontal ligament stem cells [J]. Arch Oral Biol，2020，112：104681.
[13] 杨梅，吴宁，王万春.游离脂肪酸对人牙周膜成纤维细胞增殖的影响（英文）[J].现代生物医学进展，2010，10（4）：699-702.
[14] Andrade EF，Silva VO，Moura NO，et al. Physical Exercise Improves Glycemic and Inflammatory Profile and Attenuates Progression of Periodontitis in Diabetic Rats（HFD/STZ） [J]. Nutrients，2018，10（11）：1702.
[15] Xue P，Li B，An Y，et al. Decreased MORF leads to prolonged endoplasmic reticulum stress in periodontitis-associated chronic inflammation [J]. Cell Death Differ，2016，23（11）：1862-1872.
[16] Trindade-da-Silva CA，Bettaieb A，Napimoga MH，et al. Soluble Epoxide Hydrolase Pharmacological Inhibition Decreases Alveolar Bone Loss by Modulating Host Inflammatory Response，RANK-Related Signaling，Endoplasmic Reticulum Stress，and Apoptosis [J]. J Pharmacol Exp Ther，2017，361（3）：408-416.
[17] Wang Y，Gong J，Zeng H，et al. Lipopolysaccharide Activates the Unfolded Protein Response in Human Periodontal Ligament Fibroblasts [J]. J Periodontol，2016，87（5）：e75-e81.
[18] 周宇，李晶，鲍翠玉.姜黄素纳米粒对高脂诱导的心肌细胞损伤的作用[J].中国药理学通报，2018，34（9）：1283-1288.
[19] Ou L，Sun T，Cheng Y，et al. MicroRNA-214 contributes to regulation of necroptosis via targeting ATF4 in diabetes-associated periodontitis [J]. J Cell Biochem，2019， 120（9）：14791-14803.
[20] Hagar H，Husain S，Fadda LM，et al. Inhibition of NF-kappaB and the oxidative stress -dependent caspase-3 apoptotic pathway by betaine supplementation attenuates hepatic injury mediated by cisplatin in rats [J]. Pharmacol Rep，2019，71（6）：1025-1033.
[21] Liu DD，Zhang BL，Yang JB，et al. Celastrol ameliorates endoplasmic stress-mediated apoptosis of osteoarthritis via regulating ATF-6/CHOP signalling pathway [J]. J Pharm Pharmacol，2020，72（6）：826-835.
[22] Chiu TL，Su CC. Tanshinone IIA increases protein expression levels of PERK，ATF6，IRE1alpha，CHOP，caspase3 and caspase12 in pancreatic cancer BxPC3 cellderived xenograft tumors [J]. Mol Med Rep，2017，15（5）：3259-3263.
[23] Mollazadeh H，Atkin SL，Butler AE，et al. The effect of statin therapy on endoplasmic reticulum stress [J]. Pharmacol Res，2018，137：150-158.
[24] Reddy SS，Shruthi K，Joy D，et al. 4-PBA prevents diabetic muscle atrophy in rats by modulating ER stress response and ubiquitin-proteasome system [J]. Chem Biol Interact，2019，306：70-77.