Cyclo(His-Pro) up-regulates heme oxygenase 1 via activation of Nrf2-ARE signalling

Paraquat (1,1'-dimethyl-4,4'-bipyridinium), a widely used non-selective herbicide, is a redox cycling agent with adverse effects on dopamine systems. Epidemiological data have shown that exposure to paraquat is one of the several risk factors for Parkinson's disease. We have already shown that cyclo(His-Pro), an endogenous cyclic dipeptide produced by the cleavage of the thyrotropin releasing hormone, has a cytoprotective effect through a mechanism involving Nrf2 activation that decreases production of reactive oxygen species and increases glutathione synthesis. Using primary neuronal cultures and PC12 cells as targets of paraquat neurotoxicity, we addressed whether and how cyclo(His-Pro) causes cellular protective response against paraquat-mediated cell death. We found that cyclo(His-Pro) attenuated reactive oxygen species production, and prevented glutathione depletion by up-regulating Nrf2 gene expression, triggering its nuclear accumulation and activating the expression of heme oxygenase1. These protective effects were abolished by RNA interference-mediated Nrf2 knock down whereas were unaffected by RNA interference-mediated Keap1 knock down. Inhibition of heme oxygenase activity decreased cyclo(His-Pro)-induced neuroprotection. These results suggest that cyclo(His-Pro), acting as a selective activator of the brain modulable Nrf2 pathway, may be a promising candidate as neuroprotective agent that act through induction of phase II genes.     

Increased demand for NAD+ relative to ATP drives aerobic glycolysis

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A general,fast, and sensitive micromethod for DNA determination: Application to rat and mouse liver,rat hepatoma,human leukocytes,chicken fibroblasts,and yeast cells

A fluorometric method using 3,5-diaminobenzoic acid for DNA determination in tissues, cultured cells, nucleated blood cells, and yeast cells is described. The method is general, simple, and rapid, and does not require prior DNA extraction, since tissue is directly solubilized in Triton X-100 and ammonia. The procedure is highly sensitive, and is able to measure rather accurately as little as 10 ng of DNA. It is applicable to all types of DNA structure. The DNA content determined in various tissues and cells was: 2.50 mg/g fresh rat liver, 3.32 mg/g rat diethylnitrosamine-induced hepatoma, 2.49 mg/g fresh mouse liver, 8.76 μg/10⁶ human leukocytes, 3.37 μg/10⁶ chicken fibroblasts, 2.97 μg/10⁸ haploid yeast cells, and 2.84 μg/10⁸ haploid yeast protoplasts.     

Upon the identity of Ephemera hispanica Navás, 1903 (Ephemeroptera: Ephemeridae)

Ephemera hispanica Navás, 1903 has been considered a doubtful species until recently. It is shown to be a long established synonym of E. vulgata Linnaeus, 1758.     

Aminopeptidase activity is asymmetrically distributed in selected zones of rat brain

Levels of soluble aminopeptidase (AP), measured as arylamidase activity using L-Leucine-2-Naphthylamide (Leu-2-NA) as substrate, were determined in the soluble fraction of eleven zones of rat brain. Results showed that AP activity is asymmetrically distributed in frontal cortex and hypothalamus with both left sides having significantly higher levels of AP activity, respectively, than the right sides. Simultaneously, the activities of lactate dehydrogenase (LDH) and glutamate-oxalacetate aminotransferase (GOT) were measured in the same cerebral regions; no significant difference was recorded in these activities between either side of the rat brain in any of the zones studied. Provided that aminopeptidases are involved in the degradation of some endogenously released neuropeptides, the results suggest a new mode of expression of cerebral lateralization.