聚核糖性死亡在低氧复合丙泊酚致PC12细胞损伤中的作用

王维萍; 高雯; 陈杭; 刘玲; 涂生芬; 杨飞

doi:10.16016/j.2097-0927.202111024

您当前的位置：

首页 >

文章列表页 >

聚核糖性死亡在低氧复合丙泊酚致PC12细胞损伤中的作用

基础医学 | 更新时间：2026-01-09

- 聚核糖性死亡在低氧复合丙泊酚致PC12细胞损伤中的作用
- Role of parthanatos in PC12 cell injury induced by propofol combined with hypoxic conditions
- 陆军军医大学学报 2022年44卷第10期页码：1025-1032
- 作者机构：
  
  400014 重庆，重庆医科大学附属儿童医院麻醉科，国家儿童健康与疾病临床医学研究中心，儿童发育疾病研究教育部重点实验室，儿科学重庆市重点实验室
- 作者简介：
  
  [杨飞，E-mail：270859993@qq.com YANG Fei, E-mail: 270859993@qq.com
- 基金信息：
  
  国家自然科学基金青年科学基金(31200853)
- DOI：10.16016/j.2097-0927.202111024
  中图分类号： R361.3;R364.4;R971.2
- 收稿：2021-11-02，
  
  修回：2022-01-18，
  
  纸质出版：2022-05-30
- 稿件说明：
移动端阅览
王维萍, 高雯, 陈杭, 等. 聚核糖性死亡在低氧复合丙泊酚致PC12细胞损伤中的作用[J]. 陆军军医大学学报, 2022,44(10):1025-1032.

Weiping WANG, Wen GAO, Hang CHEN, et al. Role of parthanatos in PC12 cell injury induced by propofol combined with hypoxic conditions[J]. Journal of Army Medical University, 2022, 44(10): 1025-1032.
王维萍, 高雯, 陈杭, 等. 聚核糖性死亡在低氧复合丙泊酚致PC12细胞损伤中的作用[J]. 陆军军医大学学报, 2022,44(10):1025-1032. DOI： 10.16016/j.2097-0927.202111024.

Weiping WANG, Wen GAO, Hang CHEN, et al. Role of parthanatos in PC12 cell injury induced by propofol combined with hypoxic conditions[J]. Journal of Army Medical University, 2022, 44(10): 1025-1032. DOI： 10.16016/j.2097-0927.202111024.

摘要

目的

探讨聚核糖性死亡在低氧环境下丙泊酚致PC12细胞损伤中的作用。

方法

采用经神经生长因子(nerve growth factor，NGF)诱导分化后的PC12细胞模型，用随机数字表法将细胞分为对照(NC)组(正常培养)、脂肪乳空气对照(CA)组、脂肪乳低氧对照(CH)组、丙泊酚空气(PA)组、丙泊酚低氧(PH)组、3-AB(PARP-1抑制剂)组。采用乳酸脱氢酶(Lactate dehydrogenase

LDH)试剂盒检测上清液中LDH的水平；流式细胞技术检测细胞凋亡；RT-qPCR法检测多聚ADP核糖聚合酶1(poly ADP-ribose polymerase 1

PARP-1)、细胞凋亡诱导因子(apoptosis-inducing factor

AIF)蛋白的mRNA表达水平；Western blot检测PARP-1、多聚ADP核糖(polymerized ADP-ribose

PAR)及AIF蛋白表达水平；细胞免疫荧光技术检测AIF核质分布。

结果

与NC、CA组比较，PA、PH组LDH水平及细胞凋亡增多(

0.01)，PARP-1和AIF的mRNA和蛋白表达均升高(

0.05)，胞质PAR聚合物形成增多(

0.01)，AIF核迁移显著增加(

0.01)；与CH、PA组比较，PH组LDH水平及细胞凋亡增多(

0.01)，PARP-1 mRNA和蛋白表达均升高(

0.01)，胞质PAR聚合物形成增多(

0.01)，AIF核迁移增加(

0.01)；使用PARP-1抑制剂3-AB预处理可降低低氧复合丙泊酚引起的LDH水平及细胞凋亡增加(

0.01)，同时抑制PARP-1、AIF和PAR蛋白表达上调(

0.01)。

结论

低氧环境下丙泊酚可导致PC12细胞发生聚核糖性死亡，抑制聚核糖性死亡可缓解低氧复合丙泊酚对PC12细胞的损伤。

Abstract

Objective

To explore the role of parthanatos in propofol-induced injury in PC12 cells under hypoxic conditions.

Methods

PC12 cells were induced to differentiate with mouse nerve growth factor (NGF)

and randomly divided into normal control (NC) group

lipid emulsion solvent+room air (CA) group

lipid emulsion solvent+hypoxia control (CH) group

propofol+room air (PA) group

propofol+hypoxia (PH) group

and 3-AB (PARP-1 inhibitor) group. Lactate dehydrogenase (LDH) kit and flow cytometry were adopted to detect the LDH level in the supernatant and the cell apoptosis

respectively. The mRNA levels of poly ADP-ribose polymerase 1 (PARP-1) and apoptosis-inducing factor (AIF) were determined by RT-qPCR

and the protein levels of AIF

PARP-1 and polymerized ADP-ribose (PAR) in each group were measured by Western blotting. The nuclear distribution of AIF in PC12 cells was observed by immunofluorescence assay.

Results

As compared with the NC and CA groups

the levels of LDH and apoptosis were significantly enhanced in the PA and PH groups (

0.01); the mRNA and protein levels of PARP-1 and AIF (

0.05) were increased; and the accumulation of cytoplasmic PAR (

0.01) and AIF nuclear translocation (

.01) were observed as well. In comparison with the CH and PA groups

the levels of LDH and cell apoptosis (

0.01)

the mRNA and protein expression of PARP-1 (

0.01)

the formation of cytoplasmic PAR (

0.01)

and the AIF nuclear translocation (

0.01) were all augmented in the PH group. Pretreatment with PARP-1 inhibitor 3-AB notably reversed the increase in LDH level and cell apoptosis induced by hypoxia combined with propofol (

0.01)

and restrained the up-regulation of PARP-1

AIF and PAR(

0.01).

Conclusion

Propofol causes parthanatos of PC12 cells under hypoxic conditions

and inhibition of parthanatos can alleviate the damage in PC12 cells induced by propofol combined with hypoxia.

关键词

Keywords

references

BOSNJAK Z J, LOGAN S, LIU Y N, et al . Recent insights into molecular mechanisms of propofol-induced developmental neurotoxicity: implications for the protective strategies[J ] . Anesth Analg, 2016, 12 3(5): 1286-1296. DOI: 10.1213/ANE.0000000000001544.

SNYDER C M, CHANDEL N S. Mitochondrial regulation of cell survival and death during low-oxygen conditions[J]. Antioxid Redox Signal, 2009, 11(11): 2673-2683. DOI: 10.1089/ars.2009.2730.

SUN M, YUAN R X, LIU H, et al . The effects of repeated propofol anesthesia on spatial memory and long-term potentiation in infant rats under hypoxic conditions[J ] . Genes Dis, 2020, 7(2): 245-252. DOI: 10.1016/j.gendis.2019.02.001.

TU S F, WANG X Y, YANG F, et al . Propofol induces neuronal apoptosis in infant rat brain under hypoxic conditions[J ] . Brain Res Bull, 2011, 86(1/2): 29-35. DOI: 10.1016/j.brainresbull.2011.06.017.

WANG X Z, GE P F. Parthanatos in the pathogenesis of nervous system diseases[J]. Neuroscience, 2020, 449: 241-250. DOI: 10.1016/j.neuroscience.2020.09.049.

PIAO M H, WANG Y Y, LIU N, et al . Sevoflurane exposure induces neuronal cell parthanatos initiated by DNA damage in the developing brain via an increase of intracellular reactive oxygen species[J ] . Front Cell Neurosci, 2020, 14: 583782. DOI: 10.3389/fnc el.2020.583782..

WIATRAK B, KUBIS-KUBIAK A, PIWOWAR A, et al . PC12 cell line: cell types, coating of culture vessels, differentiation and other culture conditions[J ] . Cells, 2020, 9(4): E958. DOI: 10.3390/cells9040958.

ZHONG L Y, FAN X R, SHI Z J, et al . Hyperpolarization-activated cyclic nucleotide-gated ion (HCN) channels regulate PC12 cell differentiation toward sympathetic neuron[J ] . Front Cell Neurosci, 2019, 13: 415. DOI: 10.3389/fncel.2019.00415.

CHIDAMBARAN V, COSTANDI A, D'MELLO A. Propofol: a review of its role in pediatric anesthesia and sedation[J]. CNS Drugs, 2015, 29(7): 543-563. DOI: 10.1007/s40263-015-0259-6.

JIANG L L, YANG F Y, ZHAO Q, et al . MicroRNA-665 mediates propofol-induced cell apoptosis in human stem cell-derived neurons[J ] . Bioengineered, 2019, 10(1): 493-500. DOI: 10.1080/21655979.2019.1682105.

YANG M R, WANG Y, LIANG G, et al . Alzheimer's disease presenilin-1 mutation sensitizes neurons to impaired autophagy flux and propofol neurotoxicity: role of calcium dysregulation[J ] . J Alzheimers Dis, 2019, 67(1): 137-147. DOI: 10.323 3/JAD-180858.

LONG B, LI S L, XUE H P, et al . Effects of propofol treatment in neural progenitors derived from human-induced pluripotent stem cells[J ] . Neural Plast, 2017, 2017: 9182748. DOI: 10.1155/2017/9182748.

ANDRABI S A, DAWSON T M, DAWSON V L. Mitochondrial and nuclear cross talk in cell death: parthanatos[J]. Ann N Y Acad Sci, 2008, 1147: 233-241. DOI: 10.1196/annals.1427.014.

CZAPSKI G A, CIEŚLIK M, WENCEL P L, et al . Inhibition of poly(ADP-ribose) polymerase-1 alters expression of mitochondria-related genes in PC12 cells: relevance to mitochondrial homeostasis in neurodegenerative disorders[J ] . Biochim Biophys Acta Mol Cell Res, 2018, 1865(2): 281-288. DOI: 10.1016/j.bbamcr.2017.11.003.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

Mdivi-1通过抑制过度线粒体自噬改善低氧复合丙泊酚引起的未成熟SD大鼠认知功能障碍

低氧复合丙泊酚通过铁死亡对未成熟SD大鼠海马神经元的影响

慢性低氧通过肝因子ANGPTL3介导的线粒体损伤与脂肪产热抑制降低耐寒能力

低氧抑制精子纤毛微管稳定性致精子发生障碍的分子机制研究

高原低氧改善肿瘤免疫微环境并抑制结直肠癌皮下肿瘤生长