Sialin, an anion transporter defective in sialic acid storage diseases, shows highly variable expression in adult mouse brain, and is developmentally regulated.

Sialin is a lysosomal membrane protein encoded by the SLC17A5 gene, which is mutated in patients with sialic acid storage diseases (SASD). To further understand the role of sialin in normal CNS development and in the progressive neuronal atrophy and dysmyelination seen in SASD, we investigated its normal cellular distribution in adult and developing mice. Overall, sialin showed granular immunoreactivity, consistent with a vesicular protein.

Candidate tumor-suppressor genes on chromosome arm 8p in early-onset and high-grade breast cancers.

Loss of genetic material from chromosome arm 8p occurs commonly in breast carcinomas, suggesting that this region is the site of one or more tumor-suppressor genes (TSGs). Comparative genomic hybridization analysis showed that 8p loss is more common in breast cancers from pre-menopausal compared with post-menopausal patients, as well as in high-grade breast cancers, regardless of the menopausal status. Subsequent high-resolution gene expression profiling of genes mapped to chromosome arm 8p, on an extended cohort of clinical tumor samples, indicated a similar dichotomy of breast cancer clinicopathologic types.

Cellular redox activity of coenzyme Q10: effect of CoQ10 supplementation on human skeletal muscle.

In this paper, we report results obtained from a continuing clinical trial on the effect of coenzyme Q10 (CoQ10) administration on human vastus lateralis (quadriceps) skeletal muscle. Muscle samples, obtained from aged individuals receiving placebo or CoQ10 supplementation (300mg per day for four weeks prior to hip replacement surgery) were analysed for changes in gene and protein expression and in muscle fibre type composition. Microarray analysis (Affymetrix U95A human oligonucleotide array) using a change in gene expression of 1.

Stochastic mitochondrial DNA changes: bioenergy decline in type I skeletal muscle fibres correlates with a decline in the amount of amplifiable full-length mtDNA.

Extra-long PCR (XL-PCR) was used to assess the relative concentration of functional full-length mitochondrial DNA (mtDNA) in single type I human vastus lateralis muscle fibres of defined cytochrome c oxidase (COX) activity. Type I muscle fibres rely more on mitochondrial oxidative phosphorylation for their energy demands, compared to the other common fibre types (IIa, IIab and IIb) that principally depend on glycolysis for their energy requirements. A total of 60 single type I fibres were analyzed from 15 individuals (8 males and 7 females) of various ages.

Age-related atrophy of rat soleus muscle is accompanied by changes in fibre type composition, bioenergy decline and mtDNA rearrangements.

A variety of techniques have been applied to investigate the interrelationship between age-related atrophy of rat soleus muscle and other signs of muscle aging, such as changes in muscle fibre type composition, decrease in bioenergy capacity and accumulation of mitochondrial DNA (mtDNA) arrangements. Age-related atrophy of rat soleus muscle was shown to start at the age of about 28 months. It was accompanied by a decrease in the number of slow twitch muscle fibres (type I) and an increase in the proportion of muscle fibres co-expressing slow and fast myosins (type Ic and IIc fibres).

Human aging and global function of coenzyme Q10.

In this paper, we review two parts of our recent work on human skeletal muscle. The first part mainly describes changes occurring during aging, whereas the second part discusses the functions of coenzyme Q10 (CoQ10), particularly in relation to the aging process. During the lifetime of an individual, mtDNA undergoes a variety of mutation events and rearrangements.