Sevoflurane postconditioning reduces apoptosis by activating the JAK-STAT pathway after transient global cerebral ischemia in rats

Hyun Chang Kim, Eugene Kim, Jung Il Bae, Kook Hyun Lee, Young Tae Jeon, Jung Won Hwang, Young Jin Lim, Seong Won Min, Hee Pyoung Park

Research output: Contribution to journalArticle

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Abstract

Background: The antiapoptotic effects of sevoflurane postconditioning are responsible for neuroprotection against cerebral ischemia-reperfusion injury. Phosphorylation of the Janus family tyrosine kinases (JAK) 2-signal transducers and activators of transcription (STAT) 3 pathway is linked to antiapoptosis. Here, we determined whether the antiapoptotic effects of sevoflurane postconditioning are associated with activation of the JAK2-STAT3 pathway after global transient cerebral ischemia in rats. Materials and Methods: Forty-five rats were randomly assigned to 5 groups: sham (n = 5), control (10 min of ischemia, n = 10), sevoflurane postconditioning (2 periods of sevoflurane inhalation after ischemia for 10 min, n = 10), AG490 (a JAK2 selective inhibitor, intraperitoneal administration of 40 mg/kg before ischemia, n = 10), and sevoflurane postconditioning plus AG490 group (n = 10). The number of apoptotic cells as well as the expression of JAK2, phosphorylated JAK2 (P-JAK2), STAT3, phosphorylated STAT3 (P-STAT3), Bcl-2 (antiapoptotic protein), and Bax (proapoptotic protein) were evaluated 3 days after ischemia. Results: The apoptotic cell count was significantly lower in the sevoflurane postconditioning group than in the control, AG490, and sevoflurane postconditioning plus AG490 groups. JAK2 and STAT3 levels were comparable among all 5 groups. PJAK2, P-STAT3, and Bcl-2 levels were higher and Bax levels were lower in the sevoflurane postconditioning group relative to the control, AG490, and sevoflurane postconditioning plus AG490 groups. Conclusions: Sevoflurane postconditioning reduced apoptosis by increasing P-JAK and P-STAT expression after transient global ischemia in rats, and AG490 reversed the beneficial antiapoptotic effects of sevoflurane postconditioning, suggesting that the JAK-STAT pathway may be involved in the antiapoptotic mechanism of sevoflurane postconditioning.

Original languageEnglish
Pages (from-to)37-45
Number of pages9
JournalJournal of Neurosurgical Anesthesiology
Volume29
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

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STAT2 Transcription Factor
Transient Ischemic Attack
Apoptosis
Ischemia
sevoflurane
Cell Count
TYK2 Kinase
bcl-2-Associated X Protein
STAT3 Transcription Factor

All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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Sevoflurane postconditioning reduces apoptosis by activating the JAK-STAT pathway after transient global cerebral ischemia in rats. / Kim, Hyun Chang; Kim, Eugene; Bae, Jung Il; Lee, Kook Hyun; Jeon, Young Tae; Hwang, Jung Won; Lim, Young Jin; Min, Seong Won; Park, Hee Pyoung.

In: Journal of Neurosurgical Anesthesiology, Vol. 29, No. 1, 01.01.2017, p. 37-45.

Research output: Contribution to journalArticle

Kim, Hyun Chang ; Kim, Eugene ; Bae, Jung Il ; Lee, Kook Hyun ; Jeon, Young Tae ; Hwang, Jung Won ; Lim, Young Jin ; Min, Seong Won ; Park, Hee Pyoung. / Sevoflurane postconditioning reduces apoptosis by activating the JAK-STAT pathway after transient global cerebral ischemia in rats. In: Journal of Neurosurgical Anesthesiology. 2017 ; Vol. 29, No. 1. pp. 37-45.
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abstract = "Background: The antiapoptotic effects of sevoflurane postconditioning are responsible for neuroprotection against cerebral ischemia-reperfusion injury. Phosphorylation of the Janus family tyrosine kinases (JAK) 2-signal transducers and activators of transcription (STAT) 3 pathway is linked to antiapoptosis. Here, we determined whether the antiapoptotic effects of sevoflurane postconditioning are associated with activation of the JAK2-STAT3 pathway after global transient cerebral ischemia in rats. Materials and Methods: Forty-five rats were randomly assigned to 5 groups: sham (n = 5), control (10 min of ischemia, n = 10), sevoflurane postconditioning (2 periods of sevoflurane inhalation after ischemia for 10 min, n = 10), AG490 (a JAK2 selective inhibitor, intraperitoneal administration of 40 mg/kg before ischemia, n = 10), and sevoflurane postconditioning plus AG490 group (n = 10). The number of apoptotic cells as well as the expression of JAK2, phosphorylated JAK2 (P-JAK2), STAT3, phosphorylated STAT3 (P-STAT3), Bcl-2 (antiapoptotic protein), and Bax (proapoptotic protein) were evaluated 3 days after ischemia. Results: The apoptotic cell count was significantly lower in the sevoflurane postconditioning group than in the control, AG490, and sevoflurane postconditioning plus AG490 groups. JAK2 and STAT3 levels were comparable among all 5 groups. PJAK2, P-STAT3, and Bcl-2 levels were higher and Bax levels were lower in the sevoflurane postconditioning group relative to the control, AG490, and sevoflurane postconditioning plus AG490 groups. Conclusions: Sevoflurane postconditioning reduced apoptosis by increasing P-JAK and P-STAT expression after transient global ischemia in rats, and AG490 reversed the beneficial antiapoptotic effects of sevoflurane postconditioning, suggesting that the JAK-STAT pathway may be involved in the antiapoptotic mechanism of sevoflurane postconditioning.",
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T1 - Sevoflurane postconditioning reduces apoptosis by activating the JAK-STAT pathway after transient global cerebral ischemia in rats

AU - Kim, Hyun Chang

AU - Kim, Eugene

AU - Bae, Jung Il

AU - Lee, Kook Hyun

AU - Jeon, Young Tae

AU - Hwang, Jung Won

AU - Lim, Young Jin

AU - Min, Seong Won

AU - Park, Hee Pyoung

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background: The antiapoptotic effects of sevoflurane postconditioning are responsible for neuroprotection against cerebral ischemia-reperfusion injury. Phosphorylation of the Janus family tyrosine kinases (JAK) 2-signal transducers and activators of transcription (STAT) 3 pathway is linked to antiapoptosis. Here, we determined whether the antiapoptotic effects of sevoflurane postconditioning are associated with activation of the JAK2-STAT3 pathway after global transient cerebral ischemia in rats. Materials and Methods: Forty-five rats were randomly assigned to 5 groups: sham (n = 5), control (10 min of ischemia, n = 10), sevoflurane postconditioning (2 periods of sevoflurane inhalation after ischemia for 10 min, n = 10), AG490 (a JAK2 selective inhibitor, intraperitoneal administration of 40 mg/kg before ischemia, n = 10), and sevoflurane postconditioning plus AG490 group (n = 10). The number of apoptotic cells as well as the expression of JAK2, phosphorylated JAK2 (P-JAK2), STAT3, phosphorylated STAT3 (P-STAT3), Bcl-2 (antiapoptotic protein), and Bax (proapoptotic protein) were evaluated 3 days after ischemia. Results: The apoptotic cell count was significantly lower in the sevoflurane postconditioning group than in the control, AG490, and sevoflurane postconditioning plus AG490 groups. JAK2 and STAT3 levels were comparable among all 5 groups. PJAK2, P-STAT3, and Bcl-2 levels were higher and Bax levels were lower in the sevoflurane postconditioning group relative to the control, AG490, and sevoflurane postconditioning plus AG490 groups. Conclusions: Sevoflurane postconditioning reduced apoptosis by increasing P-JAK and P-STAT expression after transient global ischemia in rats, and AG490 reversed the beneficial antiapoptotic effects of sevoflurane postconditioning, suggesting that the JAK-STAT pathway may be involved in the antiapoptotic mechanism of sevoflurane postconditioning.

AB - Background: The antiapoptotic effects of sevoflurane postconditioning are responsible for neuroprotection against cerebral ischemia-reperfusion injury. Phosphorylation of the Janus family tyrosine kinases (JAK) 2-signal transducers and activators of transcription (STAT) 3 pathway is linked to antiapoptosis. Here, we determined whether the antiapoptotic effects of sevoflurane postconditioning are associated with activation of the JAK2-STAT3 pathway after global transient cerebral ischemia in rats. Materials and Methods: Forty-five rats were randomly assigned to 5 groups: sham (n = 5), control (10 min of ischemia, n = 10), sevoflurane postconditioning (2 periods of sevoflurane inhalation after ischemia for 10 min, n = 10), AG490 (a JAK2 selective inhibitor, intraperitoneal administration of 40 mg/kg before ischemia, n = 10), and sevoflurane postconditioning plus AG490 group (n = 10). The number of apoptotic cells as well as the expression of JAK2, phosphorylated JAK2 (P-JAK2), STAT3, phosphorylated STAT3 (P-STAT3), Bcl-2 (antiapoptotic protein), and Bax (proapoptotic protein) were evaluated 3 days after ischemia. Results: The apoptotic cell count was significantly lower in the sevoflurane postconditioning group than in the control, AG490, and sevoflurane postconditioning plus AG490 groups. JAK2 and STAT3 levels were comparable among all 5 groups. PJAK2, P-STAT3, and Bcl-2 levels were higher and Bax levels were lower in the sevoflurane postconditioning group relative to the control, AG490, and sevoflurane postconditioning plus AG490 groups. Conclusions: Sevoflurane postconditioning reduced apoptosis by increasing P-JAK and P-STAT expression after transient global ischemia in rats, and AG490 reversed the beneficial antiapoptotic effects of sevoflurane postconditioning, suggesting that the JAK-STAT pathway may be involved in the antiapoptotic mechanism of sevoflurane postconditioning.

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