Search

Abstract: Rnd proteins are a family of small GTPases that have been involved in axon path finding and CNS development by their control of actin cytoskeleton dynamics. Rnd proteins are constitutively activated and, subsequently, their functions determined by their localization and expression levels. In this work we have analyzed by Western blot and immunohistochemistry the levels and localization of Rnd3/RhoE during mouse postnatal development. CNS was found to be the main tissue for RhoE protein expression, which was detected in all regions of the adult brain and spinal cord, with the highest levels in the olfactory bulb and cortex. RhoE protein levels were considerably higher in all the regions of the CNS the first 2–3 weeks of postnatal development, undergoing later a decrease that led to low levels in the adult. Immunohistochemical detection of RhoE at postnatal day 21 showed an intense and widespread labelling throughout the CNS. RhoE immunoreactivity was detected in the granular and mitral cells and anterior olfactory nuclei of the olfactory bulb and in all cerebral layers. In the striatum, diencephalon, mesencephalon, pons, medulla oblongata and spinal cord, RhoE was widely distributed with higher intensity in the motoneurones and in some brainstem nuclei such as the red nucleus or the reticulotegmental nucleus. The pyramidal cells of CA1-3 and the polymorph layer, but not the granular cells of the dentate gyrus in the hippocampus were strongly labelled. At earlier stages the labelling was nearly similar; however, a prominent labelling was detected in the cells of the rostral migratory stream and in the external granule cells of the cerebellum. Our results suggest that RhoE can play important roles in the postnatal development and maturation of the CNS, especially in the migratory processes affecting the neurones. [Copyright &y& Elsevier] more...

The arachidonic acid-derived metabolite 12-(S)hydroxyeicosatetraenoic acid (12(S)-HETE), catalyzed by 12-lipoxygenase (12-LOX, ALOX12), exhibits a variety of biological activities with implications in cardiovascular disease. Previous studies have shown higher urinary excretion of this metabolite in essential hypertension. The aim of this study was to analyze the association of polymorphisms in ALOX12 with hypertension and urinary levels of 12(S)-HETE. We studied 200 patients with essential hypertension (aged 56±1 years, mean±s.e.m., 97 males) and 166 matched controls (aged 54±1 years, 91 males). Out of six polymorphisms in the coding region of ALOX12, only R261Q determined a nonconservative amino-acid change and was evaluated by polymerase chain reaction and restriction digestion. Urinary 12(S)-HETE was measured in Sep-Pack-extracted samples using specific enzyme-linked immunosorbent assay. The distribution of genotypes of the R261Q polymorphism was significantly different between patients and controls: patients 92 (0.46) GG, 84 (0.42) GA, 24 (0.12) AA vs controls 56 (0.34) GG, 78 (0.47) GA, 32 (0.19) AA (P=0.030). On the contrary, no association was observed for two intronic polymorphisms. The urinary excretion of 12(S)-HETE (ng/mg creatinine) was significantly higher in GG homozygous patients (13.0±1.5) than in GA (8.2±1.8) or in AA (8±1.5) patients (P=0.018). These results indicate that a nonsynonymous polymorphism in ALOX12 is associated to essential hypertension and to urinary levels of 12(S)-HETE, thus suggesting a role for this gene in this disease.Kidney International (2006) 69, 526–530. doi:10.1038/sj.ki.5000147; published online 6 January 2006 [ABSTRACT FROM AUTHOR] more...