Upregulation of matrix metalloproteinase 1 and disruption of mitochondrial network in skin fibroblasts of patients with MERRF syndrome.

By using cDNA microarray and RT-PCR techniques, we investigated the genome-wide alteration of gene expression in skin fibroblasts from patients with myoclonic epilepsy and ragged-red fibers (MERRF) syndrome. By screening for the genes with altered levels of expression, we first discovered that matrix metalloproteinase 1 (MMP1) was highly induced in the primary culture of skin fibroblasts of a female patient in a four-generation family with MERRF syndrome. This phenomenon was confirmed in skin fibroblasts from three other MERRF patients harboring about 85% of mtDNA with A8344G mutation.

Chromosome positional effects of gene expressions after cellular senescence.

Normal human fibroblasts stop dividing after a limited number of cell divisions termed cellular senescence. Telomere shortening has been shown to be the main factor that causes cellular senescence, however, the molecular mechanism of how telomere shortening causes cellular senescence is unclear. Here we analyze the relationship between gene expressions and their chromosomal locations during cellular senescence.

Increased expression of manganese-superoxide dismutase in fibroblasts of patients with CPEO syndrome.

Alterations in the expression of free radical scavenging enzymes and production of reactive oxygen species (ROS) in tissue cells may contribute to the pathogenesis of mitochondrial diseases such as chronic progressive external ophthalmoplegia (CPEO) syndrome. Since the mitochondria with impaired respiratory function in affected tissues generate more ROS via electron leakage, we examined the expression levels of free radical scavenging enzymes in primary culture of muscle fibroblasts of eight patients with CPEO syndrome. The results showed that the enzyme activity and protein levels of Mn-SOD of the fibroblasts from CPEO patients were significantly increased but those of Cu,Zn-SOD, catalase and glutathione peroxidase (GPx) were not increased compared with controls.