Biomedical subjects

Sara Borniquel

Publications and source records attributed to Sara Borniquel.

4 recordsLinked to original sources

PubMed2007

Mitochondrial dysfunction in human pathologies.

The integrity of mitochondrial function is fundamental to cell life. The cell demands for mitochondria and their complex integration into cell biology, extends far beyond the provision of ATP. It follows that disturbances of mitochondrial function lead to disruption of cell function, expressed as disease or even death. Mitochondria are major producers of free radical species and also possibly of nitric oxide, and are, at the same time, major targets for oxidative damage. In this review we consider recent developments in our knowledge of how the mitochondrial production of reactive oxygen species (ROS) plays a critical role in several major human pathologies. We will also consider recent advances in our understanding of the molecular mechanisms involved in mitochondrial ROS detoxification.

Aging↗

PubMed2006

Nitric oxide regulates mitochondrial oxidative stress protection via the transcriptional coactivator PGC-1alpha.

Nitric oxide (NO) has both prooxidant and antioxidant activities in the endothelium; however, the molecular mechanisms involved are still a matter of controversy. PGC-1alpha [peroxisome proliferators-activated receptor (PPAR) gamma coactivator 1-alpha] induces the expression of several members of the mitochondrial reactive oxygen species (ROS) detoxification system. Here, we show that NO regulates this system through the modulation of PGC-1alpha expression. Short-term (<12 h) treatment of endothelial cells with NO donors down-regulates PGC-1alpha expression, whereas long-term (>24 h) treatment up-regulates it. Treatment with the NOS inhibitor l-NAME has the opposite effect. Down-regulation of PGC-1alpha by NO is mediated by protein kinase G (PKG). It is blocked by the soluble guanylate cyclase (sGC) inhibitor ODQ and the PKG inhibitor KT5823, and mimicked by the cGMP analog 8-Br-cGMP. Changes in PGC-1alpha expression are in all cases paralleled by corresponding variations in the mitochondrial ROS detoxification system. Cells that transiently overexpress PGC-1alpha from the cytomeglovirus (CMV) promoter respond poorly to NO donors. Analysis of tissues from eNOS(-/-) mice showed reduced levels of PGC-1alpha and the mitochondrial ROS detoxification system. These data suggest that NO can regulate the mitochondrial ROS detoxification system both positively and negatively through PGC-1alpha.

Animals↗

PubMed2005

Cytotoxicity and bioaccumulation of heavy metals by ciliated protozoa isolated from urban wastewater treatment plants.

We studied the cytotoxic effect of the heavy metals Cd, Zn and Cu on three different species of ciliated protozoa isolated from an urban wastewater treatment plant. The order of toxicity was Cd>Cu>>Zn or Cu>Cd>>Zn, depending on the microbial species. In bimetallic (Cd+Zn) treatments, results indicated that, in general, the presence of Zn in the same medium decreased Cd cytotoxicity. Both cellular assays and microscopic observations showed that bioaccumulation is an important mechanism of resistance to these toxic environmental pollutants in such eukaryotic microorganisms. However, bioaccumulation might not be the main mechanism involved in Cu resistance. For the first time, fluorescence methodology was applied for revealing metal deposits in the cellular cytoplasm. This microscopic method is only useful when cell cultures can be exposed to rather high metal concentrations, as in the case of Zn. Inside the ciliated protozoa exposed to sublethal concentrations of Cd or Zn, it is possible to observe diverse electron-dense granules by TEM which are not seen in controls. Problems in comparing our results on heavy metal cytotoxic effects on ciliates with already published data are exposed and discussed. The use of these eukaryotic microorganisms as potential whole cells or molecular (ciliate metallothioneins) biosensors seems to be a reasonable useful alternative for assessing metallic pollution.

Animals↗

PubMed2005

Ultrastructural alterations in ciliated protozoa under heavy metal exposure.

Transmission electron microscopy was used to study the ultrastructural changes induced by exposure to Cd or Zn in three species of ciliated protozoa: Colpoda steinii, Cyrtolophosis elongata and Drepanomonas revoluta. The main cytoplasmic alterations were partial mitochondrial degeneration, cytoplasmic vacuolisation, accumulation of membranous debris and autophagosome formation. At the nuclear level we detected nucleolar fusion in the macronucleus, and micronuclear membrane modifications. We compared these modifications with those coinciding with ciliate encystment (a differentiation process induced by environmental nutritional stress) and with changes in eukaryotic cells treated with staurosporine, a potent protein kinase inhibitor considered to be an apoptosis inducer. Exposure to heavy metals also coincided with the appearance of electron-dense accumulations in the cytoplasm, which might be related to metallothionein-mediated detoxification. The results are compared with previously reported data from ciliates and microalgae treated with heavy metals.

Animals↗