Role of parthanatos in PC12 cell injury induced by propofol combined with hypoxic conditions

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, lipi...

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Main Authors: WANG Weiping, GAO Wen, CHEN Hang, LIU Ling, TU Shengfen, YANG Fei
Format: Article
Language:zho
Published: Editorial Office of Journal of Third Military Medical University 2022-05-01
Series:Di-san junyi daxue xuebao
Subjects:
Online Access:http://aammt.tmmu.edu.cn/Upload/rhtml/202111024.htm
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author WANG Weiping
GAO Wen
CHEN Hang
LIU Ling
TU Shengfen
YANG Fei
author_facet WANG Weiping
GAO Wen
CHEN Hang
LIU Ling
TU Shengfen
YANG Fei
author_sort WANG Weiping
collection DOAJ
description 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 (P < 0.01); the mRNA and protein levels of PARP-1 and AIF (P < 0.05) were increased; and the accumulation of cytoplasmic PAR (P < 0.01) and AIF nuclear translocation (P < 0.01) were observed as well. In comparison with the CH and PA groups, the levels of LDH and cell apoptosis (P < 0.01), the mRNA and protein expression of PARP-1 (P < 0.01), the formation of cytoplasmic PAR (P < 0.01), and the AIF nuclear translocation (P < 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 (P < 0.01), and restrained the up-regulation of PARP-1, AIF and PAR(P < 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.
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spelling doaj.art-88187b55ed3840b5a0858ef30c072d232022-12-22T00:29:41ZzhoEditorial Office of Journal of Third Military Medical UniversityDi-san junyi daxue xuebao1000-54042022-05-0144101025103210.16016/j.2097-0927.202111024Role of parthanatos in PC12 cell injury induced by propofol combined with hypoxic conditionsWANG Weiping0GAO Wen1CHEN Hang2LIU Ling3 TU Shengfen4YANG Fei5Department of Anesthesiology, National Clinical Research Center of Child Health and Disease, Key Laboratory of Child Developmental Diseases of Ministry of Education, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, ChinaDepartment of Anesthesiology, National Clinical Research Center of Child Health and Disease, Key Laboratory of Child Developmental Diseases of Ministry of Education, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, ChinaDepartment of Anesthesiology, National Clinical Research Center of Child Health and Disease, Key Laboratory of Child Developmental Diseases of Ministry of Education, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, ChinaDepartment of Anesthesiology, National Clinical Research Center of Child Health and Disease, Key Laboratory of Child Developmental Diseases of Ministry of Education, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, ChinaDepartment of Anesthesiology, National Clinical Research Center of Child Health and Disease, Key Laboratory of Child Developmental Diseases of Ministry of Education, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, ChinaDepartment of Anesthesiology, National Clinical Research Center of Child Health and Disease, Key Laboratory of Child Developmental Diseases of Ministry of Education, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, ChinaObjective 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 (P < 0.01); the mRNA and protein levels of PARP-1 and AIF (P < 0.05) were increased; and the accumulation of cytoplasmic PAR (P < 0.01) and AIF nuclear translocation (P < 0.01) were observed as well. In comparison with the CH and PA groups, the levels of LDH and cell apoptosis (P < 0.01), the mRNA and protein expression of PARP-1 (P < 0.01), the formation of cytoplasmic PAR (P < 0.01), and the AIF nuclear translocation (P < 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 (P < 0.01), and restrained the up-regulation of PARP-1, AIF and PAR(P < 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.http://aammt.tmmu.edu.cn/Upload/rhtml/202111024.htmhypoxiapropofolrat adrenal pheochromocytoma cellsparthanatos
spellingShingle WANG Weiping
GAO Wen
CHEN Hang
LIU Ling
TU Shengfen
YANG Fei
Role of parthanatos in PC12 cell injury induced by propofol combined with hypoxic conditions
Di-san junyi daxue xuebao
hypoxia
propofol
rat adrenal pheochromocytoma cells
parthanatos
title Role of parthanatos in PC12 cell injury induced by propofol combined with hypoxic conditions
title_full Role of parthanatos in PC12 cell injury induced by propofol combined with hypoxic conditions
title_fullStr Role of parthanatos in PC12 cell injury induced by propofol combined with hypoxic conditions
title_full_unstemmed Role of parthanatos in PC12 cell injury induced by propofol combined with hypoxic conditions
title_short Role of parthanatos in PC12 cell injury induced by propofol combined with hypoxic conditions
title_sort role of parthanatos in pc12 cell injury induced by propofol combined with hypoxic conditions
topic hypoxia
propofol
rat adrenal pheochromocytoma cells
parthanatos
url http://aammt.tmmu.edu.cn/Upload/rhtml/202111024.htm
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