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Sevoflurane post-conditioning increases nuclear factor erythroid 2-related factor and haemoxygenase-1 expression via protein kinase C pathway in a rat model of transient global cerebral ischaemia.
Br J Anaesth. 2015 Feb; 114(2):307-18.BJ

Abstract

BACKGROUND

The antioxidant mechanism of sevoflurane post-conditioning-induced neuroprotection remains unclear. We determined whether sevoflurane post-conditioning induces nuclear factor erythroid 2-related factor (Nrf2, a master transcription factor regulating antioxidant defence genes) and haemoxygenase-1 (HO-1, an antioxidant enzyme) expression, and whether protein kinase C (PKC) is involved in Nrf2 activation, in a rat model of transient global cerebral ischaemia/reperfusion (I/R) injury.

METHODS

Eighty-six rats were assigned to five groups: sham (n=6), control (n=20), sevoflurane post-conditioning (two cycles with 2 vol% sevoflurane inhalation for 10 min, n=20), chelerythrine (a PKC inhibitor; 5 mg kg(-1) i.v. administration, n=20), and sevoflurane post-conditioning plus chelerythrine (n=20). The levels of nuclear Nrf2 and cytoplasmic HO-1 were assessed 1 or 7 days after ischaemia (n=10 each, apart from the sham group, n=3).

RESULTS

On day 1 but not day 7 post-ischaemia, Nrf2 and HO-1 expression were significantly higher in the sevoflurane post-conditioning group than in the control group. Chelerythrine administration reduced the elevated Nrf2 and HO-1 expression induced by sevoflurane post-conditioning.

CONCLUSIONS

Sevoflurane post-conditioning increased Nrf2/HO-1 expression via PKC signalling in the early phase after transient global cerebral I/R injury, suggesting that activation of antioxidant enzymes may be responsible for sevoflurane post-conditioning-induced neuroprotection in the early phase after cerebral I/R injury.

Authors+Show Affiliations

Department of Anaesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.Department of Anaesthesiology and Pain Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea.Department of Anaesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.Department of Anaesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.Department of Anaesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.Department of Anaesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.Department of Anaesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.Department of Anaesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea hppark@snu.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25163467

Citation

Lee, H, et al. "Sevoflurane Post-conditioning Increases Nuclear Factor Erythroid 2-related Factor and Haemoxygenase-1 Expression Via Protein Kinase C Pathway in a Rat Model of Transient Global Cerebral Ischaemia." British Journal of Anaesthesia, vol. 114, no. 2, 2015, pp. 307-18.
Lee H, Park YH, Jeon YT, et al. Sevoflurane post-conditioning increases nuclear factor erythroid 2-related factor and haemoxygenase-1 expression via protein kinase C pathway in a rat model of transient global cerebral ischaemia. Br J Anaesth. 2015;114(2):307-18.
Lee, H., Park, Y. H., Jeon, Y. T., Hwang, J. W., Lim, Y. J., Kim, E., Park, S. Y., & Park, H. P. (2015). Sevoflurane post-conditioning increases nuclear factor erythroid 2-related factor and haemoxygenase-1 expression via protein kinase C pathway in a rat model of transient global cerebral ischaemia. British Journal of Anaesthesia, 114(2), 307-18. https://doi.org/10.1093/bja/aeu268
Lee H, et al. Sevoflurane Post-conditioning Increases Nuclear Factor Erythroid 2-related Factor and Haemoxygenase-1 Expression Via Protein Kinase C Pathway in a Rat Model of Transient Global Cerebral Ischaemia. Br J Anaesth. 2015;114(2):307-18. PubMed PMID: 25163467.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sevoflurane post-conditioning increases nuclear factor erythroid 2-related factor and haemoxygenase-1 expression via protein kinase C pathway in a rat model of transient global cerebral ischaemia. AU - Lee,H, AU - Park,Y H, AU - Jeon,Y T, AU - Hwang,J W, AU - Lim,Y J, AU - Kim,E, AU - Park,S Y, AU - Park,H P, Y1 - 2014/08/27/ PY - 2014/8/29/entrez PY - 2014/8/29/pubmed PY - 2015/3/19/medline KW - GA-binding protein transcription factor KW - anaesthetics, inhalation KW - haeme oxygenase-1 KW - protein kinase C SP - 307 EP - 18 JF - British journal of anaesthesia JO - Br J Anaesth VL - 114 IS - 2 N2 - BACKGROUND: The antioxidant mechanism of sevoflurane post-conditioning-induced neuroprotection remains unclear. We determined whether sevoflurane post-conditioning induces nuclear factor erythroid 2-related factor (Nrf2, a master transcription factor regulating antioxidant defence genes) and haemoxygenase-1 (HO-1, an antioxidant enzyme) expression, and whether protein kinase C (PKC) is involved in Nrf2 activation, in a rat model of transient global cerebral ischaemia/reperfusion (I/R) injury. METHODS: Eighty-six rats were assigned to five groups: sham (n=6), control (n=20), sevoflurane post-conditioning (two cycles with 2 vol% sevoflurane inhalation for 10 min, n=20), chelerythrine (a PKC inhibitor; 5 mg kg(-1) i.v. administration, n=20), and sevoflurane post-conditioning plus chelerythrine (n=20). The levels of nuclear Nrf2 and cytoplasmic HO-1 were assessed 1 or 7 days after ischaemia (n=10 each, apart from the sham group, n=3). RESULTS: On day 1 but not day 7 post-ischaemia, Nrf2 and HO-1 expression were significantly higher in the sevoflurane post-conditioning group than in the control group. Chelerythrine administration reduced the elevated Nrf2 and HO-1 expression induced by sevoflurane post-conditioning. CONCLUSIONS: Sevoflurane post-conditioning increased Nrf2/HO-1 expression via PKC signalling in the early phase after transient global cerebral I/R injury, suggesting that activation of antioxidant enzymes may be responsible for sevoflurane post-conditioning-induced neuroprotection in the early phase after cerebral I/R injury. SN - 1471-6771 UR - https://www.unboundmedicine.com/medline/citation/25163467/Sevoflurane_post_conditioning_increases_nuclear_factor_erythroid_2_related_factor_and_haemoxygenase_1_expression_via_protein_kinase_C_pathway_in_a_rat_model_of_transient_global_cerebral_ischaemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0007-0912(17)31723-3 DB - PRIME DP - Unbound Medicine ER -