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

WANG Weiping; GAO Wen; CHEN Hang; LIU Ling; TU Shengfen; YANG Fei

doi:10.16016/j.2097-0927.202111024

Di-san junyi daxue xuebao (May 2022)

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

WANG Weiping,
GAO Wen,
CHEN Hang,
LIU Ling,
TU Shengfen,
YANG Fei

Affiliations

WANG Weiping: Department 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, China
GAO Wen: Department 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, China
CHEN Hang: Department 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, China
LIU Ling: Department 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, China
TU Shengfen: Department 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, China
YANG Fei: Department 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, China

DOI: https://doi.org/10.16016/j.2097-0927.202111024
Journal volume & issue: Vol. 44, no. 10
pp. 1025 – 1032

Abstract

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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.

Published in Di-san junyi daxue xuebao

ISSN: 1000-5404 (Print)
Publisher: Editorial Office of Journal of Third Military Medical University
Country of publisher: China
LCC subjects: Medicine: Medicine (General)
Website: https://aammt.tmmu.edu.cn/

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