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Medical Gas Research
Published in: Medical Gas Research 1/2012

Open Access 01-12-2012 | Research

Propofol and magnesium attenuate isoflurane-induced caspase-3 activation via inhibiting mitochondrial permeability transition pore

Authors: Yiying Zhang, Yuanlin Dong, Zhipeng Xu, Zhongcong Xie

Published in: Medical Gas Research | Issue 1/2012

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Abstract

Background

The inhalation anesthetic isoflurane has been shown to open the mitochondrial permeability transition pore (mPTP) and induce caspase activation and apoptosis, which may lead to learning and memory impairment. Cyclosporine A, a blocker of mPTP opening might attenuate the isoflurane-induced mPTP opening, lessening its ripple effects. Magnesium and anesthetic propofol are also mPTP blockers. We therefore set out to determine whether propofol and magnesium can attenuate the isoflurane-induced caspase activation and mPTP opening.

Methods

We investigated the effects of magnesium sulfate (Mg2+), propofol, and isoflurane on the opening of mPTP and caspase activation in H4 human neuroglioma cells stably transfected to express full-length human amyloid precursor protein (APP) (H4 APP cells) and in six day-old wild-type mice, employing Western blot analysis and flowcytometry.

Results

Here we show that Mg2+ and propofol attenuated the isoflurane-induced caspase-3 activation in H4-APP cells and mouse brain tissue. Moreover, Mg2+ and propofol, the blockers of mPTP opening, mitigated the isoflurane-induced mPTP opening in the H4-APP cells.

Conclusion

These data illustrate that Mg2+ and propofol may ameliorate the isoflurane-induced neurotoxicity by inhibiting its mitochondrial dysfunction. Pending further studies, these findings may suggest the use of Mg2+ and propofol in preventing and treating anesthesia neurotoxicity.
Appendix
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Literature
1.
Thies W, Bleiler L: 2011 Alzheimer's disease facts and figures. Alzheimers Dement. 2011, 7 (2): 208-244.
2.
Lunkes A, Trottier Y, Mandel JL: Pathological mechanisms in Huntington's disease and other polyglutamine expansion diseases. Essays Biochem. 1998, 33: 149-163.PubMed
3.
Namura S, et al: Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia. J Neurosci. 1998, 18 (10): 3659-3668.PubMed
4.
Holtzman DM, Deshmukh M: Caspases: a treatment target for neurodegenerative disease?. Nat Med. 1997, 3 (9): 954-955. 10.1038/nm0997-954.PubMed
5.
Kim TW, et al: Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease. Science. 1997, 277 (5324): 373-376. 10.1126/science.277.5324.373.PubMed
6.
Loetscher H, et al: Presenilins are processed by caspase-type proteases. J Biol Chem. 1997, 272 (33): 20655-20659. 10.1074/jbc.272.33.20655.PubMed
7.
Barnes NY, et al: Increased production of amyloid precursor protein provides a substrate for caspase-3 in dying motoneurons. J Neurosci. 1998, 18 (15): 5869-5880.PubMed
8.
Kovacs DM, et al: Staurosporine-induced activation of caspase-3 is potentiated by presenilin 1 familial Alzheimer's disease mutations in human neuroglioma cells. J Neurochem. 1999, 73 (6): 2278-2285.PubMed
9.
Su JH, et al: Immunohistochemical evidence for apoptosis in Alzheimer's disease. Neuroreport. 1994, 5 (18): 2529-2533. 10.1097/00001756-199412000-00031.PubMed
10.
Su JH, Deng G, Cotman CW: Bax protein expression is increased in Alzheimer's brain: correlations with DNA damage, Bcl-2 expression, and brain pathology. J Neuropathol Exp Neurol. 1997, 56 (1): 86-93. 10.1097/00005072-199701000-00009.PubMed
11.
Tesco G, et al: Depletion of GGA3 stabilizes BACE and enhances beta-secretase activity. Neuron. 2007, 54 (5): 721-737. 10.1016/j.neuron.2007.05.012.PubMedCentralPubMed
12.
Mattson MP: Contributions of mitochondrial alterations, resulting from bad genes and a hostile environment, to the pathogenesis of Alzheimer's disease. Int Rev Neurobiol. 2002, 53: 387-409.PubMed
13.
Raina AK, et al: Apoptotic promoters and inhibitors in Alzheimer's disease: Who wins out?. Prog Neuropsychopharmacol Biol Psychiatry. 2003, 27 (2): 251-254. 10.1016/S0278-5846(03)00020-4.PubMed
14.
Burguillos MA, et al: Caspase signalling controls microglia activation and neurotoxicity. Nature. 2011, 472 (7343): 319-324. 10.1038/nature09788.PubMed
15.
Eckenhoff RG, et al: Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity. Anesthesiology. 2004, 101 (3): 703-709. 10.1097/00000542-200409000-00019.PubMed
16.
Brambrink AM, et al: Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain. Anesthesiology. 2010, 112 (4): 834-841. 10.1097/ALN.0b013e3181d049cd.PubMedCentralPubMed
17.
Xie Z, et al: The common inhalation anesthetic isoflurane induces caspase activation and increases amyloid beta-protein level in vivo. Ann Neurol. 2008, 64 (6): 618-627. 10.1002/ana.21548.PubMedCentralPubMed
18.
Xie Z, et al: The common inhalation anesthetic isoflurane induces apoptosis and increases amyloid beta protein levels. Anesthesiology. 2006, 104 (5): 988-994. 10.1097/00000542-200605000-00015.PubMed
19.
Xie Z, et al: Isoflurane-induced apoptosis: a potential pathogenic link between delirium and dementia. The journals of gerontology. Series A. Biological sciences and medical sciences. 2006, 61 (12): 1300-1306.PubMed
20.
Xie Z, et al: The inhalation anesthetic isoflurane induces a vicious cycle of apoptosis and amyloid beta-protein accumulation. J Neurosci. 2007, 27 (6): 1247-1254. 10.1523/JNEUROSCI.5320-06.2007.PubMed
21.
Wei H, et al: Isoflurane and sevoflurane affect cell survival and BCL-2/BAX ratio differently. Brain Res. 2005, 1037 (1–2): 139-147.PubMed
22.
Wei H, et al: The common inhalational anesthetic isoflurane induces apoptosis via activation of inositol 1,4,5-trisphosphate receptors. Anesthesiology. 2008, 108 (2): 251-260. 10.1097/01.anes.0000299435.59242.0e.PubMed
23.
Loop T, Priebe HJ: Costs of anaesthesia. Eur J Anaesthesiol. 2005, 22 (2): 162-10.1017/S0265021505260283. author reply 162–3PubMed
24.
Zhang B, et al: The effects of isoflurane and desflurane on cognitive function in humans. Anesth Analg. 2012, 114 (2): 410-415. 10.1213/ANE.0b013e31823b2602.PubMedCentralPubMed
25.
Fournier N, Ducet G, Crevat A: Action of cyclosporine on mitochondrial calcium fluxes. J Bioenerg Biomembr. 1987, 19 (3): 297-303. 10.1007/BF00762419.PubMed
26.
Bernardi P: The permeability transition pore. Control points of a cyclosporin A-sensitive mitochondrial channel involved in cell death. Biochim Biophys Acta. 1996, 1275 (1–2): 5-9.PubMed
27.
Bernardi P, Petronilli V: The permeability transition pore as a mitochondrial calcium release channel: a critical appraisal. J Bioenerg Biomembr. 1996, 28 (2): 131-138. 10.1007/BF02110643.PubMed
28.
Hansson MJ, et al: Brain-derived respiring mitochondria exhibit homogeneous, complete and cyclosporin-sensitive permeability transition. J Neurochem. 2004, 89 (3): 715-729. 10.1111/j.1471-4159.2004.02400.x.PubMed
29.
He L, Lemasters JJ: Dephosphorylation of the Rieske iron-sulfur protein after induction of the mitochondrial permeability transition. Biochem Biophys Res Commun. 2005, 334 (3): 829-837. 10.1016/j.bbrc.2005.06.170.PubMed
30.
Nicolli A, et al: Interactions of cyclophilin with the mitochondrial inner membrane and regulation of the permeability transition pore, and cyclosporin A-sensitive channel. J Biol Chem. 1996, 271 (4): 2185-2192. 10.1074/jbc.271.4.2185.PubMed
31.
Norman KG, et al: Cyclosporine A suppresses keratinocyte cell death through MPTP inhibition in a model for skin cancer in organ transplant recipients. Mitochondrion. 2010, 10 (2): 94-101. 10.1016/j.mito.2009.10.001.PubMed
32.
Alessandri B, et al: Cyclosporin A improves brain tissue oxygen consumption and learning/memory performance after lateral fluid percussion injury in rats. J Neurotrauma. 2002, 19 (7): 829-841. 10.1089/08977150260190429.PubMed
33.
Osman MM, et al: Cyclosporine-A as a neuroprotective agent against stroke: its translation from laboratory research to clinical application. Neuropeptides. 2011, 45 (6): 359-368. 10.1016/j.npep.2011.04.002.PubMed
34.
Halestrap AP, Clarke SJ, Javadov SA: Mitochondrial permeability transition pore opening during myocardial reperfusion–a target for cardioprotection. Cardiovasc Res. 2004, 61 (3): 372-385. 10.1016/S0008-6363(03)00533-9.PubMed
35.
Wei H, Liang G, Yang H: Isoflurane preconditioning inhibited isoflurane-induced neurotoxicity. Neurosci Lett. 2007, 425 (1): 59-62. 10.1016/j.neulet.2007.08.011.PubMedCentralPubMed
36.
Ljubkovic M, et al: Isoflurane preconditioning uncouples mitochondria and protects against hypoxia-reoxygenation. Am J Physiol Cell Physiol. 2007, 292 (5): C1583-C1590.PubMed
37.
Pan C, et al: The potential dual effects of anesthetic isoflurane on hypoxia-induced caspase-3 activation and increases in beta-site amyloid precursor protein-cleaving enzyme levels. Anesth Analg. 2011, 113 (1): 145-152. 10.1213/ANE.0b013e3182185fee.PubMedCentralPubMed
38.
Xu Z, et al: The potential dual effects of anesthetic isoflurane on Abeta-induced apoptosis. Curr Alzheimer Res. 2011, 8 (7): 741-752. 10.2174/156720511797633223.PubMedCentralPubMed
39.
Zaugg M, et al: Differential effects of anesthetics on mitochondrial K(ATP) channel activity and cardiomyocyte protection. Anesthesiology. 2002, 97 (1): 15-23. 10.1097/00000542-200207000-00004.PubMed
40.
Jiang MT, et al: Isoflurane activates human cardiac mitochondrial adenosine triphosphate-sensitive K + channels reconstituted in lipid bilayers. Anesth Analg. 2007, 105 (4): 926-932. 10.1213/01.ane.0000278640.81206.92. table of contentsPubMed
41.
Zhang G, et al: Isoflurane-induced caspase-3 activation is dependent on cytosolic calcium and can be attenuated by memantine. J Neurosci. 2008, 28 (17): 4551-4560. 10.1523/JNEUROSCI.5694-07.2008.PubMedCentralPubMed
42.
Lu Y, et al: Anesthetic sevoflurane causes neurotoxicity differently in neonatal naive and Alzheimer disease transgenic mice. Anesthesiology. 2010, 112 (6): 1404-1416. 10.1097/ALN.0b013e3181d94de1.PubMedCentralPubMed
43.
Rossaint J, et al: Propofol: neuroprotection in an in vitro model of traumatic brain injury. Crit Care. 2009, 13 (2): R61-10.1186/cc7795.PubMedCentralPubMed
44.
Shu L, et al: Inhibition of neuron-specific CREB dephosphorylation is involved in propofol and ketamine-induced neuroprotection against cerebral ischemic injuries of mice. Neurochem Res. 2012, 37 (1): 49-58. 10.1007/s11064-011-0582-3.PubMed
45.
Marinov MB, et al: Neuroprotective effects of preischemia intraarterial magnesium sulfate in reversible focal cerebral ischemia. J Neurosurg. 1996, 85 (1): 117-124. 10.3171/jns.1996.85.1.0117.PubMed
46.
Zhang Y, et al: The mitochondrial pathway of anesthetic isoflurane-induced apoptosis. J Biol Chem. 2010, 285 (6): 4025-4037. 10.1074/jbc.M109.065664.PubMedCentralPubMed
47.
Zhang J, et al: 2-Deoxy-D-glucose attenuates isoflurane-induced cytotoxicity in an in vitro cell culture model of H4 human neuroglioma cells. Anesth Analg. 2011, 113 (6): 1468-1475. 10.1213/ANE.0b013e31822e913c.PubMedCentralPubMed
48.
Zhang Y, et al: Anesthetic propofol attenuates the isoflurane-induced caspase-3 activation and Abeta oligomerization. PLoS One. 2011, 6 (11): e27019-10.1371/journal.pone.0027019.PubMedCentralPubMed
49.
Culley DJ, et al: Long-term impairment of acquisition of a spatial memory task following isoflurane-nitrous oxide anesthesia in rats. Anesthesiology. 2004, 100 (2): 309-314. 10.1097/00000542-200402000-00020.PubMed
50.
Bianchi SL, et al: Brain and behavior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics. Neurobiol Aging. 2008, 29 (7): 1002-1010. 10.1016/j.neurobiolaging.2007.02.009.PubMed
51.
Rezzani R: Exploring cyclosporine A-side effects and the protective role-played by antioxidants: the morphological and immunohistochemical studies. Histol Histopathol. 2006, 21 (3): 301-316.PubMed
52.
Wu X, et al: The inhalation anesthetic isoflurane increases levels of proinflammatory TNF-alpha, IL-6, and IL-1beta. Neurobiol Aging. 2012, 33 (7): 1364-1378. 10.1016/j.neurobiolaging.2010.11.002.PubMedCentralPubMed
53.
Dingledine R, et al: The glutamate receptor ion channels. Pharmacol Rev. 1999, 51 (1): 7-61.PubMed
54.
Zhang Y, et al: Anesthetics isoflurane and desflurane differently affect mitochondrial function, learning, and memory. Ann Neurol. 2012, 71 (5): 687-698. 10.1002/ana.23536.PubMedCentralPubMed
55.
Buljubasic N, et al: Effects of halothane and isoflurane on calcium and potassium channel currents in canine coronary arterial cells. Anesthesiology. 1992, 76 (6): 990-998. 10.1097/00000542-199206000-00020.PubMed
56.
Friederich P, Benzenberg D, Urban BW: Ketamine and propofol differentially inhibit human neuronal K(+) channels. Eur J Anaesthesiol. 2001, 18 (3): 177-183.PubMed
57.
Shao H, et al: Dose-dependent protective effect of propofol against mitochondrial dysfunction in ischaemic/reperfused rat heart: role of cardiolipin. Br J Pharmacol. 2008, 153 (8): 1641-1649. 10.1038/bjp.2008.45.PubMedCentralPubMed
Metadata
Title
Propofol and magnesium attenuate isoflurane-induced caspase-3 activation via inhibiting mitochondrial permeability transition pore
Authors
Yiying Zhang
Yuanlin Dong
Zhipeng Xu
Zhongcong Xie
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Medical Gas Research / Issue 1/2012
Electronic ISSN: 2045-9912
DOI
https://doi.org/10.1186/2045-9912-2-20

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