Propofol Inhibits Caspase-3 in Astroglial Cells: Role of Heme Oxygenase-1

Abstract

Several lines of evidence have extensively demonstrated that peroxynitrite plays a pivotal role in Central Nervous System (CNS) injuries. The present study was aimed at elucidating the molecular mechanism by which propofol attenuates peroxynitrite-mediated injury in the brain. Primary cultured astroglial cells were incubated for 18 h with a known peroxynitrite donor (SIN-1,3 mM) in the presence or absence of propofol (40 microM, 80 microM and 160 microM). The protective effects of propofol were evaluated by MTT cytotoxicity assay, LDH release, and caspase-3 activation by Western blot analysis. Appropriate propofol concentrations (ranging from 40 microM to 160 microM) significantly increased HO-1 expression and attenuated SIN-1-mediated cytotoxicity and caspase-3 activation. The protective effects of propofol were mitigated by the addition of tin-mesoporphirin (SnMP), a potent inhibitor of HO activity. The addition of a specific synthetic inhibitor of NF-kappaB abolished propofol-mediated HO-1 induction, suggesting a possible role for this nuclear transcriptional factor in our experimental conditions. These findings indicate that propofol attenuates peroxynitrite-mediated apoptosis in astroglial cells, a property that may be relevant in both physiological and pathological processes in the CNS.

Propofol attenuates intestinal mucosa injury induced by intestinal ischemia-reperfusion in the rat

“…Indeed, propofol has been shown to significantly increase heme oxygenase production in astrocytes and astroglial cells. 27,28 Heme oxygenase is a molecule with antioxidant properties that has been demonstrated to play a critical role in intestinal ischemic preconditioning that mediates protection against intestinal mucosal injury and the subsequent systemic inflammatory response. 29,30 Therefore, propofol may have initiated a preconditioning-like effect that is characterized by an increase of the endogenous antioxidant defenses, such as the increase of heme oxygenase and SOD activities.…”

Functional impairment of the auditory pathway after perinatal asphyxia and the short-term effect of perinatal propofol anesthesia in lambs

“…Of these, propofol is one of the most promising agents in mediating neuroprotection after hypoxicischemic insults in adult patients and animals (15)(16)(17)(18). However, in the developing brain, anesthetic agents have also been shown to induce apoptosis in newborn animal models (19).…”

Pharmacological Induction of Heme Oxygenase-1 Reduces KB Cell Viability:Role of Carbon Monoxide

“…As such, scavenging ROS with phenolic phytochemicals should inhibit these cellular processes and thus cancer cell proliferation. However, we and others [18,27] suggested a potential novel aspect in the mode of action of phenolic phytochemicals; that is, the ultimate stimulation of Hmox1 pathway is likely to account for the established and powerful antioxidant/antiinflammatory properties of these polyphenols. Our recent studies [28] evidenced that KB cells are more sensitive to the Chilean propolis ethanolic extract, containing a high concentration of CAPE and exhibiting interesting antioxidant activity, when compared to others tumor cell lines such as Caco-2 and DU-145.…”

“…Hmox-2 is constitutively expressed in blood vessels, endothelium, testis and most other tissues and its levels are relatively unaffected by factors inducing Hmox1 [15]. Hmox1 is expressed under basal conditions and its expression and activity can be induced by oxidative stress-causing agents, heavy metals and polyphenolic compounds such as rosolic acid, caffeic acid phenethyl ester (CAPE) [16][17][18][19][20]. This is an active compound of propolis, a natural honeybee product exhibiting a spectrum of biological activities, including anti-microbial, anti-inflammatory, anti-oxidant and anti-tumoral actions [21][22][23].…”