» Articles » PMID: 20007710

The Mitochondrial Pathway of Anesthetic Isoflurane-induced Apoptosis

Overview
Journal J Biol Chem
Specialty Biochemistry
Date 2009 Dec 17
PMID 20007710
Citations 112
Authors
Affiliations
Soon will be listed here.
Abstract

The common inhalation anesthetic isoflurane has been shown to induce apoptosis, which then leads to accumulation of beta-amyloid protein, the hallmark feature of Alzheimer disease neuropathogenesis. The underlying molecular mechanism of the isoflurane-induced apoptosis is largely unknown. We, therefore, set out to assess whether isoflurane can induce apoptosis by regulating Bcl-2 family proteins, enhancing reactive oxygen species (ROS) accumulation, and activating the mitochondrial pathway of apoptosis. We performed these studies in cultured cells, primary neurons, and mice. Here we show for the first time that treatment with 2% isoflurane for 6 h can increase pro-apoptotic factor Bax levels, decrease anti-apoptotic factor Bcl-2 levels, increase ROS accumulation, facilitate cytochrome c release from the mitochondria to the cytosol, induce activation of caspase-9 and caspase-3, and finally cause apoptosis as compared with the control condition. We have further found that isoflurane can increase the mRNA levels of Bax and reduce the mRNA levels of Bcl-2. The isoflurane-induced ROS accumulation can be attenuated by the intracellular calcium chelator BAPTA. Finally, the anesthetic desflurane does not induce activation of mitochondrial pathway of apoptosis. These results suggest that isoflurane may induce apoptosis through Bcl-2 family proteins- and ROS-associated mitochondrial pathway of apoptosis. These findings, which have identified at least partially the molecular mechanism by which isoflurane induces apoptosis, will promote more studies aimed at studying the potential neurotoxic effects of anesthetics.

Citing Articles

The antioxidative effect of STAT3 involved in cellular vulnerability to isoflurane.

Yang Y, Song S, Wang H, Ma Z, Gao Q BMC Neurosci. 2024; 25(1):75.

PMID: 39633283 PMC: 11619428. DOI: 10.1186/s12868-024-00911-x.


Unraveling the role and mechanism of mitochondria in postoperative cognitive dysfunction: a narrative review.

Zhang Z, Yang W, Wang L, Zhu C, Cui S, Wang T J Neuroinflammation. 2024; 21(1):293.

PMID: 39533332 PMC: 11559051. DOI: 10.1186/s12974-024-03285-3.


Sophoricoside attenuates neuronal injury and altered cognitive function by regulating the LTR-4/NF-κB/PI3K signalling pathway in anaesthetic-exposed neonatal rats.

Yang L, Xu Y, Zhang W Arch Med Sci. 2024; 20(1):248-254.

PMID: 38414447 PMC: 10895946. DOI: 10.5114/aoms.2020.93638.


Towards a potent and rapidly reversible Dexmedetomidine-based general anesthetic.

Xie Z, Fong R, Fox A PLoS One. 2023; 18(9):e0291827.

PMID: 37751454 PMC: 10522005. DOI: 10.1371/journal.pone.0291827.


Research Advances of Mitochondrial Dysfunction in Perioperative Neurocognitive Disorders.

Chen M, Yan R, Ding L, Luo J, Ning J, Zhou R Neurochem Res. 2023; 48(10):2983-2995.

PMID: 37294392 DOI: 10.1007/s11064-023-03962-4.


References
1.
Yang H, Liang G, Hawkins B, Madesh M, Pierwola A, Wei H . Inhalational anesthetics induce cell damage by disruption of intracellular calcium homeostasis with different potencies. Anesthesiology. 2008; 109(2):243-50. PMC: 2598762. DOI: 10.1097/ALN.0b013e31817f5c47. View

2.
Zhang B, Dong Y, Zhang G, Moir R, Xia W, Yue Y . The inhalation anesthetic desflurane induces caspase activation and increases amyloid beta-protein levels under hypoxic conditions. J Biol Chem. 2008; 283(18):11866-75. PMC: 2335348. DOI: 10.1074/jbc.M800199200. View

3.
Xie Z, Dong Y, Maeda U, Moir R, Inouye S, Culley D . Isoflurane-induced apoptosis: a potential pathogenic link between delirium and dementia. J Gerontol A Biol Sci Med Sci. 2007; 61(12):1300-6. DOI: 10.1093/gerona/61.12.1300. View

4.
Lee T, Wolozin B, Weiss K, Bednar M . Assessment of the emergence of Alzheimer's disease following coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty. J Alzheimers Dis. 2005; 7(4):319-24. DOI: 10.3233/jad-2005-7408. View

5.
Xie Z, Dong Y, Maeda U, Moir R, Xia W, Culley D . The inhalation anesthetic isoflurane induces a vicious cycle of apoptosis and amyloid beta-protein accumulation. J Neurosci. 2007; 27(6):1247-54. PMC: 6673586. DOI: 10.1523/JNEUROSCI.5320-06.2007. View