Propofol protects rat astroglial cells against tert-butyl hydroperoxide-induced cytotoxicity; the effect on histone and cAMP-response-element-binding protein (CREB) signalling.
Propofol can be potentially beneficial in oxidative stress related malignancies as neurodegenerative diseases and traumatic brain injury but its signalling pathways are poorly understood. In this study effect of propofol on astroglial signalling in oxidative stress was evaluated. Ten days old cultures of rat astroglial cells were treated for 1 hour with t-butyl hydroperoxide (tBHP) to induce oxidative stress following by 1 hour propofol. We measured cytotoxicity, changes in cell growth and apoptosis as well as alterations in expression and acetylation of chromatin core H3 and H4 histone proteins and changes in native and phosphorylated cAMP-response-element-binding protein (CREB). tBHP induced limited cytotoxicity, increased apoptosis, decreased glutamine synthetase and enolase activities, decreased nuclear CREB, CREB-P and histone proteins but unchanged cytosolic CREB and histone acetyltransferase (HDAC) expression. Propofol clearly protected the cells against tBPH-induced toxicity, normalized alterations in cell growth, restored to some extent glial enzyme activities and reduced apoptotic cell numbers. Also, propofol restored H3 but not H4 expression/activation, but was without effect on decreased nuclear CREB expression/activation. These data show that oxidative stress in cultured astroglia significantly affects nuclear CREB and histone proteins and point to the protective role of propofol.
Holownia
A
A
Department of Clinical Pharmacology, Medical University of Bialystok, Bialystok, Poland. Holow_Sinai@hotmail.com
Mroz
R M
RM
Wielgat
P
P
Skiepko
A
A
Sitko
E
E
Jakubow
P
P
Kolodziejczyk
A
A
Braszko
J J
JJ
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002843:Chromatin / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000302:isolation & purification / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D020122:tert-Butylhydroperoxide / Q000633:toxicity*
D018686:Anesthetics, Intravenous; D002843:Chromatin; D017362:Cyclic AMP Response Element-Binding Protein; D006657:Histones; D020122:tert-Butylhydroperoxide; D051548:Histone Acetyltransferases; D010751:Phosphopyruvate Hydratase; D005974:Glutamate-Ammonia Ligase; D015742:Propofol