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Phosphodiesterase 4 Inhibitor Roflumilast Protects Rat Hippocampal Neurons from Sevoflurane Induced Injury via Modulation of MEK/ERK Signaling Pathway.
Cell Physiol Biochem. 2018; 45(6):2329-2337.CP

Abstract

BACKGROUND/AIMS

Sevoflurane, a commonly used volatile anesthetic, recently has been found has neurotoxicity in the central nervous system of neonatal rodents. This study aimed to reveal whether phosphodiesterase 4 (PDE-4) inhibitor roflumilast has protective functions in sevoflurane-induced nerve damage.

METHODS

Hippocampal neurons were isolated from juvenile rats, and were exposed to sevoflurane with or without roflumilast treatment. Cell viability and apoptosis were respectively assessed by CCK-8 and flow cytometry. Western blot analysis was performed to detect the protein expressions of apoptosis-related factors, and core factors in MEK/ERK and mTOR signaling pathways.

RESULTS

Toxic effects of sevoflurane on hippocampal neurons were observed, as cell viability was reduced, apoptotic cell rate was increased, Bcl-2 was down-regulated, and Bax, cleaved caspase-3 and -9 were up-regulated after 1% sevoflurane exposure for 16 h. Sevoflurane exhibited a temporarily (less than 16 h) inhibitory effect on MEK/ERK pathway, but has no impact on mTOR pathway. Roflumilast promoted the release of cAMP and down-regulated the protein expression of PDE-4. Roflumilast (1 µM) alone has no impact on viability and apoptosis of hippocampal neurons. However, roflumilast increased cell viability and deceased apoptosis in sevoflurane-injured neurons. Besides, roflumilast could recover sevoflurane-induced deactivation of MEK/ERK pathway.

CONCLUSION

To conclude, this study demonstrated a neuroprotective role of roflumilast in sevoflurane-induced nerve damage. Roflumilast promoted hippocampal neurons viability, and reduced apoptosis possibly via modulation of MEK/ERK signaling pathway.

Authors+Show Affiliations

Department of Anesthesiology, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.Department of Pathology, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.Department of Anesthesiology, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.Department of Anesthesiology, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.Department of Anesthesiology, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.Department of Anesthesiology, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.Department of Anesthesiology, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29550808

Citation

Peng, Sheng, et al. "Phosphodiesterase 4 Inhibitor Roflumilast Protects Rat Hippocampal Neurons From Sevoflurane Induced Injury Via Modulation of MEK/ERK Signaling Pathway." Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, vol. 45, no. 6, 2018, pp. 2329-2337.
Peng S, Yan HZ, Liu PR, et al. Phosphodiesterase 4 Inhibitor Roflumilast Protects Rat Hippocampal Neurons from Sevoflurane Induced Injury via Modulation of MEK/ERK Signaling Pathway. Cell Physiol Biochem. 2018;45(6):2329-2337.
Peng, S., Yan, H. Z., Liu, P. R., Shi, X. W., Liu, C. L., Liu, Q., & Zhang, Y. (2018). Phosphodiesterase 4 Inhibitor Roflumilast Protects Rat Hippocampal Neurons from Sevoflurane Induced Injury via Modulation of MEK/ERK Signaling Pathway. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 45(6), 2329-2337. https://doi.org/10.1159/000488180
Peng S, et al. Phosphodiesterase 4 Inhibitor Roflumilast Protects Rat Hippocampal Neurons From Sevoflurane Induced Injury Via Modulation of MEK/ERK Signaling Pathway. Cell Physiol Biochem. 2018;45(6):2329-2337. PubMed PMID: 29550808.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phosphodiesterase 4 Inhibitor Roflumilast Protects Rat Hippocampal Neurons from Sevoflurane Induced Injury via Modulation of MEK/ERK Signaling Pathway. AU - Peng,Sheng, AU - Yan,Hong-Zhu, AU - Liu,Pei-Rong, AU - Shi,Xiao-Wei, AU - Liu,Chun-Liang, AU - Liu,Qi, AU - Zhang,Yu, Y1 - 2018/03/13/ PY - 2017/08/03/received PY - 2018/01/16/accepted PY - 2018/3/20/pubmed PY - 2018/6/21/medline PY - 2018/3/19/entrez KW - CAMP KW - MEK/ERK pathway KW - Nerve damage KW - Phosphodiesterase 4 inhibitor (PDE-4i) KW - Roflumilast KW - Sevoflurane SP - 2329 EP - 2337 JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JO - Cell. Physiol. Biochem. VL - 45 IS - 6 N2 - BACKGROUND/AIMS: Sevoflurane, a commonly used volatile anesthetic, recently has been found has neurotoxicity in the central nervous system of neonatal rodents. This study aimed to reveal whether phosphodiesterase 4 (PDE-4) inhibitor roflumilast has protective functions in sevoflurane-induced nerve damage. METHODS: Hippocampal neurons were isolated from juvenile rats, and were exposed to sevoflurane with or without roflumilast treatment. Cell viability and apoptosis were respectively assessed by CCK-8 and flow cytometry. Western blot analysis was performed to detect the protein expressions of apoptosis-related factors, and core factors in MEK/ERK and mTOR signaling pathways. RESULTS: Toxic effects of sevoflurane on hippocampal neurons were observed, as cell viability was reduced, apoptotic cell rate was increased, Bcl-2 was down-regulated, and Bax, cleaved caspase-3 and -9 were up-regulated after 1% sevoflurane exposure for 16 h. Sevoflurane exhibited a temporarily (less than 16 h) inhibitory effect on MEK/ERK pathway, but has no impact on mTOR pathway. Roflumilast promoted the release of cAMP and down-regulated the protein expression of PDE-4. Roflumilast (1 µM) alone has no impact on viability and apoptosis of hippocampal neurons. However, roflumilast increased cell viability and deceased apoptosis in sevoflurane-injured neurons. Besides, roflumilast could recover sevoflurane-induced deactivation of MEK/ERK pathway. CONCLUSION: To conclude, this study demonstrated a neuroprotective role of roflumilast in sevoflurane-induced nerve damage. Roflumilast promoted hippocampal neurons viability, and reduced apoptosis possibly via modulation of MEK/ERK signaling pathway. SN - 1421-9778 UR - https://www.unboundmedicine.com/medline/citation/29550808/Phosphodiesterase_4_Inhibitor_Roflumilast_Protects_Rat_Hippocampal_Neurons_from_Sevoflurane_Induced_Injury_via_Modulation_of_MEK/ERK_Signaling_Pathway_ L2 - https://www.karger.com?DOI=10.1159/000488180 DB - PRIME DP - Unbound Medicine ER -