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M Coma

Publications and source records attributed to M Coma.

6 recordsLinked to original sources

Lack of oestrogen protection in amyloid-mediated endothelial damage due to protein nitrotyrosination.

Amyloid beta-peptide (Abeta) cytotoxicity, the hallmark of Alzheimer's disease, implicates oxidative stress in both neurons and vascular cells, particularly endothelial cells. Consequently, antioxidants have shown neuroprotective activities against Abeta-induced cytotoxicity. Among the different antioxidants used in both in vitro and in vivo studies, 17beta-oestradiol (E2) has garnered the most attention. Oestrogen attenuated Abeta(E22Q)-induced toxicity in neurons but failed to protect endothelial cells. Here we show that E2-mediated activation of endothelial nitric oxide synthase (eNOS) increases the production of nitric oxide (NO), which, under Abeta(E22Q)-induced oxidative damage, results in the formation of peroxynitrite and increased nitration of tyrosine residues. Inhibition of eNOS prevents nitrotyrosination and permits E2-mediated protection against Abeta(E22Q) on endothelial cells. The main nitrotyrosinated proteins in the presence of E2 and Abeta(E22Q) were identified by MALDI-TOF mass spectrometry. These proteins are key players in the regulation of energy production, cytoskeletal integrity, protein metabolism and protection against oxidative stress. Our data highlight the potential damaging consequences of E2 in vascular disorders dealing with oxidative stress conditions, such as cerebral amyloid angiopathy, stroke and ischaemia-reperfusion conditions.

Aged↗

The physiology and pathophysiology of nitric oxide in the brain.

Nitric oxide (NO) is a molecule with pleiotropic effects in different tissues. NO is synthesized by NO synthases (NOS), a family with four major types: endothelial, neuronal, inducible and mitochondrial. They can be found in almost all the tissues and they can even co-exist in the same tissue. NO is a well-known vasorelaxant agent, but it works as a neurotransmitter when produced by neurons and is also involved in defense functions when it is produced by immune and glial cells. NO is thermodynamically unstable and tends to react with other molecules, resulting in the oxidation, nitrosylation or nitration of proteins, with the concomitant effects on many cellular mechanisms. NO intracellular signaling involves the activation of guanylate cyclase but it also interacts with MAPKs, apoptosis-related proteins, and mitochondrial respiratory chain or anti-proliferative molecules. It also plays a role in post-translational modification of proteins and protein degradation by the proteasome. However, under pathophysiological conditions NO has damaging effects. In disorders involving oxidative stress, such as Alzheimer's disease, stroke and Parkinson's disease, NO increases cell damage through the formation of highly reactive peroxynitrite. The paradox of beneficial and damaging effects of NO will be discussed in this review.

Animals↗

Different Kv2.1/Kv9.3 heteromer expression during brain and lung post-natal development in the rat.

The Kv2.1/Kv9.3 heteromer generates an O2 sensitive potassium channel and induces a slow deactivation that has important consequences for brain and lung physiology. We examined the developmental regulation of Kv2.1 and Kv9.3 mRNAs in brain and lung. Both genes followed parallel expression patterns in brain, increasing progressively through post-natal life. In lung, however, the expression of the two genes followed opposite trends: Kv2.1 transcripts decreased, while Kv9.3 mRNA increased. The Kv9.3/Kv2.1 ratio shows that while in brain the expression of both genes followed a similar pattern, the relative abundance of Kv9.3 increased steadily through post-natal life in lung. Furthermore, there is selective regulation of gene expression during the suckling-weaning transition. Our results suggest that different Kv9.3/Kv2.1 ratios could have physiological implications in both organs during post-natal development, and that diet composition and selective tissue-specific insulin regulation modulate the expression of Kv2.1 and Kv9.3.

Animals↗

One-step reverse transcription polymerase chain reaction for semiquantitative analysis of mRNA expression.

Analysis of mRNA expression is one of the main targets of scientific research. However, its quantification can be difficult, especially when dealing with low-expression mRNAs (ionic channels, carriers, receptors, etc.) or when only small samples are available (human biopsies). Here we suggest an easy, rapid and reliable method to assess semiquantitative changes in mRNA that combines several technical improvements: i) one-step reverse transcription polymerase chain reaction (RT-PCR) from total RNA; ii) addition of ethidium bromide to the gel, which provides a more homogeneous binding to DNA; iii) direct capture of the gel image using a charged-coupled device camera and then saving the image on computer before quantification, which increases resolution and thus improves and shortens the analysis; and iv) the use of 18S rRNA as a control, which is especially useful when samples from activation, differentiation and proliferation models are used. The technique was validated by checking the system conditions of image capturing and quantification. This was corroborated by a study of Kvl.3 ion channel expression in the brain. In these conditions, the wide range of PCR cycles and total RNA allows us to correlate relative gene expression and direct input of the target gene.

Animals↗

[Prevalence of xerostomia in the general population].

OBJECTIVE: Principally, to establish the prevalence of xerostomia in the general population and, second, to find the association of xerostomia with the consumption of tranquillizers and anti-depression, anti-allergy, anti-Hypertension and hypnotic drugs. DESIGN: A crossover study of prevalence. SETTING: The urban area of Sant Joan Despí, Barcelona. PARTICIPANTS: Random sample, stratified by age and gender (268 people). MEASUREMENTS AND MAIN RESULTS: A telephone survey on xerostomia and drugs intake was conducted. Prevalence in the population of xerostomia was 9.7%. There was a linear relationship between being older and greater prevalence of xerostomia. The differences found for gender was not significant. There was an association between xerostomia and intake of the aforesaid drugs. CONCLUSIONS: The high prevalence of xerostomia and its association with commonly used drugs should arouse doctors to seek adequate solutions.

Adolescent↗