In this review, we address the regulatory and toxic role of ·NO along several pathways, from the gut to the brain. Initially, we address the role on ·NO in the regulation of mitochondrial respiration with emphasis on the possible contribution to Parkinson’s disease via mechanisms that involve its interaction with a major dopamine metabolite, DOPAC. In parallel with initial discoveries of the inhibition of mitochondrial respiration by ·NO, it became clear the potential for toxic ·NO-mediated mechanisms involving the production of more reactive species and the post-translational modification of mitochondrial proteins. Accordingly, we have proposed a novel mechanism potentially leading to dopaminergic cell death, providing evidence that NO synergistically interact with DOPAC in promoting cell death via mechanisms that involve GSH depletion. The modulatory role of NO will be then briefly discussed as a master regulator on brain energy metabolism. The energy metabolism in the brain is central to the understanding of brain function and disease. The core role of ·NO in the regulation of brain metabolism and vascular responses is further substantiated by discussing its role as a mediator of neurovascular coupling, the increase in local microvessels blood flow in response to spatially restricted increase of neuronal activity. The many facets of NO as intracellular and intercellular messenger, conveying information associated with its spatial and temporal concentration dynamics, involve not only the discussion of its reactions and potential targets on a defined biological environment but also the regulation of its synthesis by the family of nitric oxide synthases. More recently, a novel pathway, out of control of NOS, has been the subject of a great deal of controversy, the nitrate:nitrite:NO pathway, adding new perspectives to ·NO biology. Thus, finally, this novel pathway will be addressed in connection with nitrate consumption in the diet and the beneficial effects of protein nitration by reactive nitrogen species.
In 46,XY individuals, testes are determined by the activity of the SRY gene (sex-determining region Y), located on the short arm of the Ychromosome. The other genetic components of the cascade
that leads to testis formation are unknown and may be located on the Xchromosome or on the autosomes. Evidence for the existence
of several loci associated with failure of male sexual development is indicated by reports of 46,XY gonadal dysgenesis associated
with structural abnormalities of the Xchromosome or of autosomes (chromosomes9, 10, 11 and 17). In this report, we describe
the investigation of a child presenting with multiple congenital abnormalities, mental retardation and partial testicular
failure. The patient had a homogeneous de novo 46,XY,inv dup(9)(pter→p24.1::p21.1 →p23.3::p24.1→qter) chromosome complement.
No deletion was found by either cytogenetic or molecular analysis. The SRY gene and DSS region showed no abnormalities. Southern blotting dosage analysis with 9p probes and fluorescent in situ hybridisation data
indicated that the distal breakpoint of the duplicated fragment was located at 9p24.1, proximal to the SNF2 gene. We therefore suggest that a gene involved in normal testicular development and/or maintenance is present at this position
on chromosome 9.
Received: 20 January 1997 / Accepted: 5 November 1997 相似文献
Abstract. Contrary to current assumptions, the reflex blood of two-spot ladybirds, Adalia bipunctata , and seven-spot ladybirds, Coccinella septempunctata , contains haemocyte-like cells. Furthermore, DNA can be extracted and amplified from coccinellid reflex blood, confirming the presence of haemocyte-like cells and demonstrating a nondestructive method of DNA extraction. 相似文献
A case of plasma cell granuloma of the tongue in an otherwise symptomless 48-year-old caucasian female is reported. The polyclonal nature of the plasmocytes was revealed by immunostaining of kappa and lambda light chains. Electron microscopic observations showed typical mature plasmocytes. A parasitic etiology of this type of lesion is suggested. 相似文献