Expression and subcellular distribution of native estrogen receptor β in murine C2C12 cells and skeletal muscle tissue

We have recently described the expression and intracellular localization of ER α in murine C2C12 cells and skeletal muscle tissue. In separate studies, a protective role of 17β-estradiol against apoptosis exerted mainly at the mitochondrial level was also shown in the C2C12 muscle cell line. However, this functional evidence was in accordance with the participation of ER β. We have then here investigated the expression and subcellular distribution of native ER β in similar skeletal muscle cultured cells and tissue developed in vivo. ER β was detected by immunoblotting using specific antibodies and ligand blot analysis after subcellular fractionation. Immunolocalization was confirmed using conventional and confocal microscopy. ER β was found to a great extent in mitochondria and in lower amounts in the cytosolic fraction, differently to ER α which localizes in microsomes, cytosol, mitochondria, and also in the nucleus of muscle tissue. ER β expression was also demonstrated by RT-PCR. Finally, the mitochondrial localization of native ER β in C2C12 muscle cells was corroborated after transient transfection with specific ER β siRNAs. These data raise the possibility that the antiapoptotic action of 17β-estradiol in muscle cells may be related in part to a direct action of the hormone on mitochondria through ER β.     

Differential impact of ageing on cellular and humoral immunity to a persistent murine γ-herpesvirus

Background  

Oncogenic γ-herpesviruses establish life-long infections in their hosts and control of these latent infections is dependent on continual immune surveillance. Immune function declines with age, raising the possibility that immune control of γ-herpesvirus infection becomes compromised with increasing age, allowing viral reactivation and/or increased latent load, both of which are associated with the development of malignancies.     

Ca2+ signaling down-regulation in ageing and Alzheimer's disease: why is Ca2+ so difficult to measure?

Ca2+ signaling is a central process in brain function, but the direction of its change in ageing and in the presymptomatic stages of Alzheimer's disease has been controversial. A great deal of studies have been interpreted as supportive to the current hypothesis that intracellular Ca2+ levels are steadily increased in ageing. We, however, believe that, although current studies have provided valuable knowledge for the mechanisms of the signal transduction process, they have not furnished relevant information regarding the global Ca2+ changes in the ageing brain, because the cognition-related Ca2+ pulses exist only in the intact brain.     

Medicinal herbs and antioxidants: potential of Rhinacanthus nasutus for disease treatment?

This review covers the biological activities of the medicinal herb, Rhinacanthus nasutus, which is part of the Acanthaceae family. This herb and the compounds isolated from it have the potential to be used for the treatment of a vast array of diseases, including neurological, (such as Alzheimer’s, Parkinson’s and depression), viral and bacterial infections (such as hepatitis and herpes virus), skin disorders, and control sugar levels in diabetic patients. Many diseases involve oxidative stress, particularly neurological diseases, where oxidative stress leads to neurodegeneration. Medicinal herbs such as R. nasutus appear to be effective at protecting against such oxidative stress. Herein we discuss the potential mechanisms by which they have their antioxidant effects, and their effects on other cellular pathways, which are involved in various disease states.     

The Utah paradigm on animal models of skeletal disorders: quo vadis?

Skeletal disorders that need effective studies in suitable animal models include "osteoporosis", arthroses and hard and soft tissue healing. For people doing or analyzing such studies this article provides a brief overview and some salient implications of the Utah paradigm of skeletal physiology. The article leaves discussing and resolving any disagreements and controversies about such things to other times, places and people.     

Sex and gonadal hormones in mouse models of Alzheimer’s disease: what is relevant to the human condition?

Biologic sex and gonadal hormones matter in human aging and diseases of aging such as Alzheimer’s – and the importance of studying their influences relates directly to human health. The goal of this article is to review the literature to date on sex and hormones in mouse models of Alzheimer’s disease (AD) with an exclusive focus on interpreting the relevance of findings to the human condition. To this end, we highlight advances in AD and in sex and hormone biology, discuss what these advances mean for merging the two fields, review the current mouse model literature, raise major unresolved questions, and offer a research framework that incorporates human reproductive aging for future studies aimed at translational discoveries in this important area. Unraveling human relevant pathways in sex and hormone-based biology may ultimately pave the way to novel and urgently needed treatments for AD and other neurodegenerative diseases.     

Genomics and policymaking: from static models to complex systems?

In the 20 years following the launching of the Human Genome Project, socio-ethical and legal responses to the policy issues raised have varied across jurisdictions. There seems, however, to be a move away from the more static, classical responses that characterized the first decade to a more epigenetic and complex one. The latter policy approach better reflects the dynamic nature of the science itself.     

p53 and ageing: too much of a good thing?

A recent report by Tyner et al.(1) suggests that p53 is bad for longevity. Heterozygotic mice carrying a p53 mutation that apparently enhances the stability of the wild-type protein showed shorter lifespans and faster ageing while also developing fewer tumours. This fits with the idea that cellular ageing is the price paid for better protection against unlimited proliferation of cancer cells. But other work shows that there is a strong positive association between DNA repair-mediated protection against cancer and ageing. So what are we to make of the new data with regard to overall understanding of the mechanisms of ageing?     

Tackling neurodegenerative diseases: animal models of Alzheimer’s disease and Parkinson’s disease

Our ageing society is confronted with a dramatic increase in incidence of age-related neurodegenerative diseases; biomedical research leading to novel therapeutic strategies is crucial to address this problem. Animal models of neurodegenerative conditions are invaluable in improving our understanding of the molecular basis of pathology, potentially revealing novel targets for intervention. Here, we review transgenic animal models of Alzheimer’s and Parkinson’s disease reported in mice, zebrafish, Caenorhabditis elegans and Drosophila melanogaster. This information will enable researchers to compare different animal models targeting disease-associated molecules by genomic engineering and to facilitate the development of novel animal models for any particular study, depending on the ultimate research goals.     

The actin cytoskeleton: a key regulator of apoptosis and ageing?

Evidence from many organisms has shown that the accumulation of reactive oxygen species (ROS) has a detrimental effect on cell well-being. High levels of ROS have been linked to programmed cell death pathways and to ageing. Recent reports have implicated changes to the dynamics of the actin cytoskeleton in the release of ROS from mitochondria and subsequent cell death.     

Differential morphology and composition of inclusions in the R6/2 mouse and PC12 cell models of Huntington’s disease

The histological hallmark feature of Huntington’s disease (HD) and other polyglutamine repeat diseases is the presence of intracellular inclusions. Much work has been devoted to trying to determine the relationship between inclusion formation and neuronal injury. However, little attention has been paid to the variability and characteristics of inclusions themselves. Here, we characterize the morphological and biochemical composition of inclusions in both a transgenic mouse model (R6/2 line) and an inducible cell culture model of HD (iPC12Q74). We identified several morphologically distinct kinds of inclusions in different locations (nuclei, cytoplasm and cellular processes). Ubiquitin colocalized completely with all of these inclusions in both the iPC12Q72 and R6/2 models. In the inclusions in iPC12Q74 cells, the 20S and 11S proteasome subunits colocalized variably, and the 19S subunit did not colocalize at all. In inclusions in R6/2 mouse neurons, the 20S subunit colocalized completely, but neither the 11S nor the 19S subunits colocalized at all. While the role of inclusions in the pathogenesis of HD continues to be debated, we suggest that the content and structure of inclusions vary considerably, not only from cell to cell but even within individual cells. Their role in the pathogenesis of HD is likely to depend on their location as well as their composition.     

Natural flavonoid silibinin promotes the migration and myogenic differentiation of murine C2C12 myoblasts via modulation of ROS generation and down-regulation of estrogen receptor α expression

Molecular and Cellular Biochemistry - Skeletal muscle regeneration is a complex process, involving the proliferation, migration, and differentiation of myoblasts. Recent studies suggest that some...     

Oxidative stress and antioxidants: a link to disease and prevention?

The thrust of this presentation takes a more programmatic approach and gives an overview of the programs at the NIH and the NCI that have a broad nutritional and basic science undercurrent and outline. Also discussed briefly are some areas of general concern that are under investigation in the nutrition group and are included in the group's outreach efforts among professional and academic organizations. The overarching focus of these efforts is to stress the importance of nutrition as a potential modulator of health/disease risks associated with genetic predisposition and environmentally induced disease from diet, lifestyle and exposure to pollutants.     

Lipooxygenase inhibition in osteoarthritis: a potential symptomatic and disease modifying effect?

5-Loxin is a compound extracted from an ancient herb that might be considered as a potent lipooxygenase inhibitor. The results observed in a preliminary trial suggest a highly intriguing clinically relevant symptomatic effect contrasting with a poor bioavailability of this compound. Moreover, in this trial, a statistically significant decrease in matrix metalloproteinase enzyme serum level suggests that, in addition to the observed symptomatic effect, such a compound might have a disease modifying effect in osteoarthritis. Further studies are required both to confirm the symptomatic efficacy and acceptable safety profile and to evaluate the potential chondromodulating effect of this compound.