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Journal of Anesthesia

Erschienen in:

10.11.2017 | Original Article

Pink1 attenuates propofol-induced apoptosis and oxidative stress in developing neurons

verfasst von: Chao Liang, Fang Du, Jing Cang, Zhanggang Xue

Erschienen in: Journal of Anesthesia | Ausgabe 1/2018

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Abstract

Background

The underlying mechanisms of propofol-induced neurotoxicity in developing neurons are still not completely understood. We examined the role of PTEN-induced kinase 1 (Pink1), an antioxidant protein, in propofol-induced apoptosis in developing neurons.

Materials and methods

Primary hippocampal neurons isolated from neonatal Sprague–Dawley rats were exposed to propofol 20 μM for 2, 4, 6 and 12 h. Subsequently, neurons underwent overexpression and knockdown of Pink1, followed by propofol exposure (20 μM, 6 h). Neuron apoptosis was detected by terminal transferase deoxyuridine triphosphate-biotin nick-end labeling (TUNEL). Reactive oxygen species (ROS) production in neurons was detected by using a 2,7-dichlorodihydro-fluorescein diacetate probe and target protein or mRNA levels were analyzed by Western blotting or real-time polymerase chain reaction.

Results

Propofol treatment time-dependently increased the number of TUNEL-positive neurons and the expression levels of cleaved caspase-3 and B-cell lymphoma 2 (BcL-2) associated X protein, but decreased expression levels of BcL-2. Furthermore, propofol treatment time-dependently reduced the expression levels of Pink1 mRNA and protein. ROS production and the markers of oxidative stress, 2,4-dinitrophenol and 4-hydroxynonenal, were increased by propofol treatment. However, these propofol-induced changes were significantly restored by Pink1 overexpression.

Conclusions

Pink1 plays an important role in neuronal apoptosis induced by propofol. Our results may provide some new insights in propofol-induced neurotoxicity in developing neurons.

Bosnjak ZJ, Logan S, Liu Y, Bai X. Recent insights into molecular mechanisms of propofol-induced developmental neurotoxicity: implications for the protective strategies. Anesth Analg. 2016;123:1286–96.CrossRefPubMedPubMedCentral

Bai X, Yan Y, Canfield S, Muravyeva MY, Kikuchi C, Zaja I, Corbett JA, Bosnjak ZJ. Ketamine enhances human neural stem cell proliferation and induces neuronal apoptosis via reactive oxygen species-mediated mitochondrial pathway. Anesth Analg. 2013;116:869–80.CrossRefPubMedPubMedCentral

Han XD, Li M, Zhang XG, Xue ZG, Cang J. Single sevoflurane exposure increases methyl-CpG island binding protein 2 phosphorylation in the hippocampus of developing mice. Mol Med Rep. 2015;11:226–30.CrossRefPubMed

Wei H. The role of calcium dysregulation in anesthetic-mediated neurotoxicity. Anesth Analg. 2011;113:972–4.CrossRefPubMedPubMedCentral

Cui Y, Ling-Shan G, Yi L, Xing-Qi W, Xue-Mei Z, Xiao-Xing Y. Repeated administration of propofol upregulated the expression of c-Fos and cleaved-caspase-3 proteins in the developing mouse brain. Indian J Pharmacol. 2011;43:648–51.PubMedPubMedCentral

Unoki M, Nakamura Y. Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway. Oncogene. 2001;20:4457–65.CrossRefPubMed

Exner N, Treske B, Paquet D, Holmstrom K, Schiesling C, Gispert S, Carballo-Carbajal I, Berg D, Hoepken HH, Gasser T, Kruger R, Winklhofer KF, Vogel F, Reichert AS, Auburger G, Kahle PJ, Schmid B, Haass C. Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin. J Neurosci. 2007;27:12413–8.CrossRefPubMed

Jendrach M, Gispert S, Ricciardi F, Klinkenberg M, Schemm R, Auburger G. The mitochondrial kinase PINK1, stress response and Parkinson’s disease. J Bioenerg Biomembr. 2009;41:481–6.CrossRefPubMed

McLelland GL, Soubannier V, Chen CX, McBride HM, Fon EA. Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control. EMBO J. 2014;33:282–95.PubMedPubMedCentral

10.

Pilsl A, Winklhofer KF. Parkin, PINK1 and mitochondrial integrity: emerging concepts of mitochondrial dysfunction in Parkinson’s disease. Acta Neuropathol. 2012;123:173–88.CrossRefPubMed

11.

Li L, Hu GK. Pink1 protects cortical neurons from thapsigargin-induced oxidative stress and neuronal apoptosis. Biosci Rep. 2015;35:e00174.PubMedPubMedCentral

12.

Zhang Y, Dong Y, Wu X, Lu Y, Xu Z, Knapp A, Yue Y, Xu T, Xie Z. The mitochondrial pathway of anesthetic isoflurane-induced apoptosis. J Biol Chem. 2010;285:4025–37.CrossRefPubMed

13.

Wang C, Zhang X, Liu F, Paule MG, Slikker W Jr. Anesthetic-induced oxidative stress and potential protection. Sci World J. 2010;10:1473–82.CrossRef

14.

Arena G, Gelmetti V, Torosantucci L, Vignone D, Lamorte G, De Rosa P, Cilia E, Jonas EA, Valente EM. PINK1 protects against cell death induced by mitochondrial depolarization, by phosphorylating Bcl-xL and impairing its pro-apoptotic cleavage. Cell Death Differ. 2013;20:920–30.CrossRefPubMedPubMedCentral

15.

Twaroski DM, Yan Y, Zaja I, Clark E, Bosnjak ZJ, Bai X. Altered mitochondrial dynamics contributes to propofol-induced cell death in human stem cell-derived neurons. Anesthesiology. 2015;123:1067–83.CrossRefPubMedPubMedCentral

16.

Lau CF, Ho YS, Hung CH, Wuwongse S, Poon CH, Chiu K, Yang X, Chu LW, Chang RC. Protective effects of testosterone on presynaptic terminals against oligomeric beta-amyloid peptide in primary culture of hippocampal neurons. Biomed Res Int. 2014;2014:103906.PubMedPubMedCentral

17.

Kang BR, Kim H, Nam SH, Yun EY, Kim SR, Ahn MY, Chang JS, Hwang JS. CopA3 peptide from Copris tripartitus induces apoptosis in human leukemia cells via a caspase-independent pathway. BMB Rep. 2012;45:85–90.CrossRefPubMed

18.

Wang H, Joseph JA. Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med. 1999;27:612–6.CrossRefPubMed

19.

Jevtovic-Todorovic V, Hartman RE, Izumi Y, Benshoff ND, Dikranian K, Zorumski CF, Olney JW, Wozniak DF. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci. 2003;23:876–82.PubMed

20.

Viviand X, Berdugo L, De La Noe CA, Lando A, Martin C. Target concentration of propofol required to insert the laryngeal mask airway in children. Paediatr Anaesth. 2003;13:217–22.CrossRefPubMed

21.

Varveris DA, Morton NS. Target controlled infusion of propofol for induction and maintenance of anaesthesia using the paedfusor: an open pilot study. Paediatr Anaesth. 2002;12:589–93.CrossRefPubMed

22.

Hume-Smith HV, Sanatani S, Lim J, Chau A, Whyte SD. The effect of propofol concentration on dispersion of myocardial repolarization in children. Anesth Analg. 2008;107:806–10.CrossRefPubMed

23.

Xiong M, Li J, Alhashem HM, Tilak V, Patel A, Pisklakov S, Siegel A, Ye JH, Bekker A. Propofol exposure in pregnant rats induces neurotoxicity and persistent learning deficit in the offspring. Brain Sci. 2014;4:356–75.CrossRefPubMedPubMedCentral

24.

Creeley C, Dikranian K, Dissen G, Martin L, Olney J, Brambrink A. Propofol-induced apoptosis of neurones and oligodendrocytes in fetal and neonatal rhesus macaque brain. Br J Anaesth. 2013;110(Suppl 1):i29–38.CrossRefPubMedPubMedCentral

25.

Pearn ML, Hu Y, Niesman IR, Patel HH, Drummond JC, Roth DM, Akassoglou K, Patel PM, Head BP. Propofol neurotoxicity is mediated by p75 neurotrophin receptor activation. Anesthesiology. 2012;116:352–61.CrossRefPubMedPubMedCentral

26.

Ola MS, Nawaz M, Ahsan H. Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem. 2011;351:41–58.CrossRefPubMed

27.

Dubinina EE, Dadali VA. Role of 4-hydroxy-trans-2-nonenal in cell functions. Biochemistry (Mosc). 2010;75:1069–87.CrossRef

28.

Dagda RK, Pien I, Wang R, Zhu J, Wang KZ, Callio J, Banerjee TD, Dagda RY, Chu CT. Beyond the mitochondrion: cytosolic PINK1 remodels dendrites through protein kinase A. J Neurochem. 2014;128:864–77.CrossRefPubMed

29.

Morais VA, Verstreken P, Roethig A, Smet J, Snellinx A, Vanbrabant M, Haddad D, Frezza C, Mandemakers W, Vogt-Weisenhorn D, Van Coster R, Wurst W, Scorrano L, De Strooper B. Parkinson’s disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic function. EMBO Mol Med. 2009;1:99–111.CrossRefPubMedPubMedCentral

30.

Rojas-Charry L, Cookson MR, Nino A, Arboleda H, Arboleda G. Downregulation of Pink1 influences mitochondrial fusion-fission machinery and sensitizes to neurotoxins in dopaminergic cells. Neurotoxicology. 2014;44:140–8.CrossRefPubMedPubMedCentral

31.

Qi Z, Yang W, Liu Y, Cui T, Gao H, Duan C, Lu L, Zhao C, Zhao H, Yang H. Loss of PINK1 function decreases PP2A activity and promotes autophagy in dopaminergic cells and a murine model. Neurochem Int. 2011;59:572–81.CrossRefPubMed

32.

Stiles BL. PI-3-K and AKT: onto the mitochondria. Adv Drug Deliv Rev. 2009;61:1276–82.CrossRefPubMed

33.

Timmons S, Coakley MF, Moloney AM, O’Neill C. Akt signal transduction dysfunction in Parkinson’s disease. Neurosci Lett. 2009;467:30–5.CrossRefPubMed

34.

Sanchez-Mora RM, Arboleda H, Arboleda G. PINK1 overexpression protects against C2-ceramide-induced CAD cell death through the PI3K/AKT pathway. J Mol Neurosci. 2012;47:582–94.CrossRefPubMed

Titel: Pink1 attenuates propofol-induced apoptosis and oxidative stress in developing neurons
verfasst von: Chao Liang
Fang Du
Jing Cang
Zhanggang Xue
Publikationsdatum: 10.11.2017
Verlag: Springer Japan
Erschienen in: Journal of Anesthesia / Ausgabe 1/2018
Print ISSN: 0913-8668
Elektronische ISSN: 1438-8359
DOI: https://doi.org/10.1007/s00540-017-2431-2

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Pink1 attenuates propofol-induced apoptosis and oxidative stress in developing neurons

Abstract

Background

Materials and methods

Results

Conclusions

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Springer Medizin

Abstract

Background

Materials and methods

Results

Conclusions

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