Propofol Attenuates Peroxynitrite-mediated DNA Damage and Apoptosis in Cultured Astrocytes: An Alternative Protective Mechanism

  title={Propofol Attenuates Peroxynitrite-mediated DNA Damage and Apoptosis in Cultured Astrocytes: An Alternative Protective Mechanism},
  author={Rosaria Acquaviva and Agata Campisi and Paolo Murabito and Giuseppina Raciti and Roberto Avola and Salvatore Mangiameli and Ilenia Musumeci and Maria Luisa Barcellona and Angelo Vanella and Giovanni Li Volti},
Background:The concentration of peroxynitrite in the brain increases after central nervous system injuries. The authors hypothesized that propofol, because of its particular chemical structure, mitigates the effects of peroxynitrite-mediated oxidative stress and apoptosis by the induction of heme oxygenase (HO)-1 in primary cultured astroglial cells. Methods:Primary cultured astroglial cells were incubated for 18 h with a known peroxynitrite donor (3 mm SIN-1) in the presence or absence of… 

Propofol attenuation of hydrogen peroxide‐mediated oxidative stress and apoptosis in cultured cardiomyocytes involves haeme oxygenase‐1

Propofol can protect cardiomyocytes against H2O2‐mediated cytotoxicity in a dose‐dependent manner and increase haeme oxygenase‐1 expression, which may partly mediate the cytoprotective effects of propofol.

Preventive role of propofol in hypoxia/reoxygenation-induced apoptotic H9c2 rat cardiac myoblast cell death.

It is reported that propofol protects cardiac H9c2 cells from hypoxia/reoxygenation-induced cell death by attenuating the phosphorylation of extracellular signal-regulated kinases (ERKs) and by up-regulating heme oxygenase 1 (HO-1) expression levels.

Propofol protects against oxidative-stress-induced COS-7 cell apoptosis by inducing autophagy

PPC has a protective effect on H2O2-induced COS-7 cell apoptosis, which is mediated by autophagy activation, and pretreatment with 3-MA inhibited the protective effect of propofol during apoptosis.

Propofol-Induced Protection of SH-SY5Y Cells against Hydrogen Peroxide Is Associated with the HO-1 via the ERK Pathway

The results suggest that the ERK pathway plays an important role in the regulation of propofol-mediated antioxidant effects in SH-SY5Y cells.

Propofol Protects Hepatic L02 Cells from Hydrogen Peroxide-Induced Apoptosis via Activation of Extracellular Signal-Regulated Kinases Pathway

It is demonstrated that propofol protects hepatic L02 cells from H2O2-induced apoptosis, partly through activating the MEK-ERK pathway and further suppressing Bad and Bax expression.

Propofol exerts hippocampal neuron protective effects via up-regulation of metallothionein-3

It is shown that propofol is neuroprotective in H/R model on hippocampal neuron cells and that it may act by up-regulation of MT-3, a growth inhibitory factor that exists mainly in the central nervous system.

Propofol protects against hydrogen peroxide-induced oxidative stress and cell dysfunction in human umbilical vein endothelial cells

It is concluded that propofol, by inhibiting p38 MAPK and NF-κB activity, decreasing NOS expression, reducing NO production, could protect HUVECs which are exposed to oxidative stress and becoming dysfunctional.



Peroxynitrite-induced apoptosis in photoreceptor cells

Results show that peroxynitrite induces apoptosis in photoreceptor cells and that such retinal damage appears to be mediated by caspase-3, and that the apoptotic process can be minimized by peroxlynitrite scavenger urate, as well as by the casp enzyme inhibitor Z-VAD-fmk.

Peroxynitrite and caspase-3 expression after ischemia/reperfusion in mouse cardiac arrest model.

The present findings suggest that peroxynitrite generated by cerebral ischemia/ reperfusion was strongly cytotoxic and induced neuronal cell death (apoptosis) mediated by caspase-3.

Effects of propofol on endothelial cells subjected to a peroxynitrite donor (SIN‐1)

It is concluded that propofol protects endothelial cells against the toxicity of ONOO− and can be partially attributed to its scavenging effect on peroxynitrite, a property that might be relevant in pathological situations involving a significant contribution of peroxlynitrite to tissue damage.

Endothelial dysfunction in a rat model of endotoxic shock. Importance of the activation of poly (ADP-ribose) synthetase by peroxynitrite.

Data suggest that PARS plays a role in peroxynitrite-induced cytotoxicity, but at very high levels of oxidant exposure, PARS-independent cytotoxic mechanisms become predominant.

Cystamine inhibits transglutaminase and caspase‐3 cleavage in glutamate‐exposed astroglial cells

It is demonstrated that prolonged exposure to glutamate of cultured astrocytes caused an increase in the expression of tissue transglutaminase (tTG), and this effect was prevented by preincubation with GYKI 52466, an antagonist of AMPA/KA receptors.

In vivo and in vitro apoptosis of human thymocytes are associated with nitrotyrosine formation.

The results support the notion of a physiologic role for peroxynitrite in human thymocyte apoptosis and nitrotyrosine formation, as shown by messenger RNA levels, protein analysis, and nitrite production in the supernatants.

Peroxynitrite‐Induced Alterations in Synaptosomal Membrane Proteins

Investigation of damage to brain neocortical synaptosomal membrane proteins and the oxidation‐sensitive enzyme glutamine synthetase caused by exposure to ONOO shows that ONOO‐ can oxidatively modify both membranous and cytosolic proteins, affecting both their physical and chemical nature.

Immunocytochemical localization and expression of heme oxygenase-1 in primary astroglial cell cultures during differentiation: effect of glutamate.