ALDH2 mediates both the detoxification of reactive aldehydes such as acetaldehyde and 4-hydroxy-2-nonenal
and the bioactivation of nitroglycerin to nitric oxide. In addition, chronic nitrate treatment results in ALDH2 inhibition and contributes to nitrate tolerance. Our laboratory recently identified ALDH2 to be a key mediator of endogenous cytoprotection. We reported that ALDH2 is phosphorylated and activated by the survival kinase protein kinase C epsilon and found a strong inverse correlation between ALDH2 activity and infarct size. We also identified a small molecule ALDH2 activator which reduces myocardial infarct size induced by ischemia/reperfusion in vivo. In this review, we discuss evidence that ALDH2 is a key mediator of endogenous survival signaling in the heart, suggest possible cardioprotective mechanisms mediated by ALDH2 and Tanespimycin nmr discuss potential clinical implications of these findings. (Trends
Cardiovasc Med 2009;19:158-164) (C) 2009, Elsevier Inc.”
“Early maternal deprivation (MD), 24 h of dam-litter separation on postnatal day (PND) 9, has been proposed as a suitable animal model to investigate some neuropsychiatric disorders with a base in neurodevelopment that also compromises metabolic and endocrine homeostasis. Atypical antipsychotics are frequently prescribed to children and adolescents as first-line treatment for several mental disorders despite the adverse metabolic effects frequently reported. However, persistent long-term effects after adolescent Selleck Cilengitide drug therapy have been scarcely investigated. In the present study we aimed to investigate the long-lasting metabolic selleck compound and behavioral effects of MD in combination with the administration of an atypical antipsychotic, i.e. olanzapine, during adolescence.
For that purpose, male and female Wistar rats not exposed (control group, Co) and exposed to the MD protocol were administered with oral olanzapine (Olan, 7.5 mg/kg/day) or vehicle (Vh, 1 mM acetic acid) in drinking water from PND 28 to PND 49. Body weight
gain, glycaemia and plasma triglyceride (TG) levels were evaluated as relevant metabolic parameters. MD significantly diminished body weight gain, while Olan administration only induced a subtle decrease in body weight gain among female animals in the long-term. Olan discontinuation decreased plasma TG levels in adult rats, an effect that was counteracted by neonatal exposure to the MD protocol. Both MD and Olan treatment impaired cognitive function in the novel object recognition test, although no interaction between treatments was observed. Neither MD nor Olan administration affected psychotic-related symptoms evaluated in the prepulse inhibition task, although animals treated with Olan showed an increased reactivity to the first acoustic stimulus. MD diminished the corticosterone stress-induced response among females, and reduced the expression of CB1 receptors in the hippocampus of both male and female rats.