Cisplatin (cisPt) use in chemotherapy is limited by the occurrence of a severe nephrotoxicity. Both autophagy and apoptosis seem to contribute in kidney response to cisPt, however their cross-talk is ...still controversial, since the role played by autophagy (cytoprotective or harmful) and the cellular site driving their switch, are still unclear. Here, we used a multidisciplinary approach to study the correlation between autophagy and apoptosis in renal NRK-52E cells exposed to cisPt.
We showed two “sensitivity-thresholds” to cisPt, stating whether apoptosis or autophagy would develop: 10
μM dose of cisPt activated autophagy that preserved cell homeostasis; however 3-methyladenine co-administration affected cell viability and induced apoptosis. In contrast, 50
μM cisPt determined cell death by apoptosis, whereas the pre-conditioning with taurine contributed to cell rescue, delaying apoptosis and maintaining autophagy. Hence, autophagy protects NRK-52E cells from cisPt injury. By studying the expression of ER specific hallmarks, such as GRP78, GRP94 and GADD153/CHOP, we found a possible pivotal role of ER signaling modulation in the crosstalk between autophagy and apoptosis induced by cisPt. To the best of our knowledge, this is the first demonstration that taurine enhances autophagic protection against apoptosis by reducing ER stress, thus making it possible to develop new strategies to reduce severe cisPt-induced side-effects such as nephrotoxicity.
► Both autophagy and apoptosis characterize renal cell response against the chemotherapic drug cisPt. ► Identified two “sensitivity-thresholds” to cisPt, where only apoptosis or autophagy will develop. ► Autophagy activation grants cytoprotection to renal cells. ► ER signaling plays a pivotal role in cisPt-induced switch between autophagy and apoptosis. ► ER stress modulators may enhance autophagic cell protective response against apoptosis.
The extra-cellular matrix of the gingival tissue plays an important role in the homeostasis of dental implants. In this work we have studied immunohistochemically the distribution of collagen ...I–III–IV–V, tenascin, metalloproteinases (MMP) 1-3-8-13 and TIMP-1 in three groups of patients: (1) subjects with natural teeth (healthy periodontal tissue), (2) subjects with normal peri-implant mucosa and (3) subjects with clinically evident peri-implantitis. The immunolabelling for collagen I–III–IV showed a similar pattern in all three groups. The labelling for collagen V increased in lamina propria of healthy peri-implant tissue and peri-implantitis. Tenascin immunolabelling in healthy and peri-implant tissues was scattered in lamina propria. In peri-implantitis tenascin immunolabelling increased mainly near to the basal lamina. The MMP-1-3-8 and TIMP-1 immunolabelling were very faint and localized in the stroma in all three groups. In healthy and peri-implant tissues MMP-13 immunolabelling was found in the lamina propria whereas in peri-implantitis MMP-13 immunolabelling was also in epithelium. On the whole, these data suggest that in the extracellular matrix of peri-implantitis there are alterations of collagen V, tenascin and MMP-13 patterns.
The effects of high-potency statins on renal function are controversial. To address the impact of statins on renal morpho-functional aspects, normotensive young mice were treated with rosuvastatin ...(Rvs). Moreover, because statins may impair mitochondrial function, mice received either dietary supplementation with an amino acid mixture enriched in essential amino acids (EAAm), which we previously demonstrated to increase mitochondrial biogenesis in muscle or an unsupplemented control diet for 1 month. Mitochondrial biogenesis and function, apoptosis, and insulin signaling pathway events were studied, primarily in cortical proximal tubules. By electron microscopy analysis, mitochondria were more abundant and more heterogeneous in size, with dense granules in the inner matrix, in Rvs- and Rvs plus EAAm-treated animals. Rvs administration increased protein kinase B and endothelial nitric oxide synthase phosphorylation, but the mammalian target of rapamycin signaling pathway was not affected. Rvs increased the expression of sirtuin 1, peroxisome proliferator-activated receptor γ coactivator-1α, cytochrome oxidase type IV, cytochrome c, and mitochondrial biogenesis markers. Levels of glucose-regulated protein 75 (Grp75), B-cell lymphoma 2, and cyclin-dependent kinase inhibitor 1 were increased in cortical proximal tubules, and expression of the endoplasmic reticulum–mitochondrial chaperone Grp78 was decreased. EAAm supplementation maintained or enhanced these changes. Rvs promotes mitochondrial biogenesis, with a probable anti-apoptotic effect. EAAm boosts these processes and may contribute to the efficient control of cellular energetics and survival in the mouse kidney. This suggests that appropriate nutritional interventions may enhance the beneficial actions of Rvs, and could potentially prevent chronic renal side effects.
Sleep disorders are common in older individuals and are most prevalent in those who are institutionalized. Sleep complaints are often comorbid with medical and neuro-psychiatric illness and ...associated with polypharmacy. Various studies show an association between sleep disorders and altered levels of inflammatory cytokines, especially IL-6. In this study, an objective sleep analysis was performed using actigraphy, and IL-6 measurements in saliva in 61 older people residing in long-term nursing homes (72.1% women). Almost half (49.2%) of the people had no or mild cognitive impairment, and the rest suffered from moderate to severe dementia, mainly due to Alzheimer's disease (25 out of 31 individuals). A significant correlation was found between salivary IL6 and sleep parameters; e.g., less salivary IL-6 had significantly (
< 0.05) worse sleep efficiency and more night awakenings. In turn, actigraphy detected alterations in people with dementia in average sleep time, daily bedtime, and average daily time out of bed. There was no significant correlation between these sleep patterns and the total number of psychotropic drugs. No significant differences were found in salivary IL-6 between individuals with or without dementia. These results should be considered in future research with institutionalized people to detect sleep disturbances and to establish interventions aimed to improve sleep quality.
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