Propofol inhibits aquaporin 4 expression through a protein kinase C-dependent pathway in an astrocyte model of cerebral ischemia/reoxygenation

BACKGROUND: Aquaporin 4 (AQP4) plays a key role in maintaining water balance in the central nervous system, and its dysfunction may lead to brain edema. Previous studies have suggested that propofol may be involved in neuroprotection by preventing brain edema. In this study, we examined the effects of propofol on edema and assessed its neuroprotective actions in an oxygen and glucose deprivation (OGD) model of cultured rat astrocytes. We assessed the effects of propofol on AQP4 expression and the possible role of the protein kinase C (PKC) pathway on this effect.

METHODS: Neocortical astrocytes were exposed to OGD in an anaerobic chamber. After 6 h of OGD exposure, astrocytes were subsequently subjected to 24 h of reoxygenation. Propofol was added during the OGD phase of the model. Cell morphology was assessed by light microscopy. Astrocyte viability was assessed by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide absorbency (optical density value) and the percentage of lactate dehydrogenase released by injured astrocytes. AQP4 expression was evaluated with Western blot analysis. To investigate the possible mechanism of propofol's effects on AQP4 expression, cultured astrocytes were pretreated for 24 h with the PKC activator, 12-O-tetradecanoylphorbol 13-acetate, before the propofol treatment/OGD 6 h/reoxygenation 24 h.

RESULTS: We found by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide testing that astrocyte viability began to decrease after about 4 h of OGD exposure and decreased to 60% after 6 h of OGD. When 6 h of OGD was followed by 24 h of reoxygenation, cell viability was further decreased. AQP4 expression was attenuated after 6 h of OGD exposure but was reversed and exceeded baseline levels after 24 h of reoxygenation. Propofol dose-dependently reduced cell death assessed by lactate dehydrogenase test (P < 0.05), and 10 muM propofol significantly down-regulated AQP4 expression in astrocytes after 6 h of OGD followed by 24 h of reoxygenation (P < 0.01). Prolonged (24 h) pretreatment with the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate before OGD significantly reversed the effect of propofol on AQP4 expression (P < 0.01).

CONCLUSION: Propofol, administered during OGD, provided neuroprotective effects and down-regulated AQP4 expression in the OGD/reoxygenation model of cultured rat astrocytes. Activation of the PKC pathway may block the effects of propofol.

Medienart:	E-Artikel

Erscheinungsjahr:	2009
Erschienen:	2009

Enthalten in:	Zur Gesamtaufnahme - volume:109
Enthalten in:	Anesthesia and analgesia - 109(2009), 5 vom: 03. Nov., Seite 1493-9

Sprache:	Englisch

Beteiligte Personen:	Zhu, Sheng-Mei [VerfasserIn] Xiong, Xiao-Xing [VerfasserIn] Zheng, Yue-Ying [VerfasserIn] Pan, Cai-Fei [VerfasserIn]

Links:	Volltext

Themen:	Aqp4 protein, rat Aquaporin 4 EC 1.1.1.27 EC 2.7.11.13 Enzyme Activators Glucose IY9XDZ35W2 Journal Article L-Lactate Dehydrogenase NI40JAQ945 Neuroprotective Agents Oxygen Propofol Protein Kinase C Research Support, Non-U.S. Gov't S88TT14065 Tetradecanoylphorbol Acetate YI7VU623SF

Anmerkungen:	Date Completed 05.11.2009 Date Revised 21.11.2013 published: Print Citation Status MEDLINE

doi:	10.1213/ANE.0b013e3181b893f3

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	NLM19218783X