Increased platelet activation in sleep apnea subjects with intermittent hypoxemia.

Purpose: Obstructive sleep apnea (OSA) is independently associated with increased risk for stroke and other cardiovascular diseases. Since activated platelets play an important role in cardiovascular disease, the objective of this study was to determine whether platelet reactivity was altered in OSA subjects with intermittent nocturnal hypoxemia.

Methods: Thirty-one subjects, without hypertension or cardiovascular disease and not taking medication, participated in the study.

The m.3243A>G mtDNA mutation is pathogenic in an in vitro model of the human blood brain barrier.

MELAS is a common mitochondrial disease frequently associated with the m.3243A>G point mutation in the tRNA(Leu(UUR)) of mitochondrial DNA and characterized by stroke-like episodes with vasogenic edema and lactic acidosis. The pathogenic mechanism of stroke and brain edema is not known.

Evidence for nuclear modifier gene in mitochondrial cardiomyopathy.

Mitochondrial DNA (mtDNA) inheritance and maintenance and function of the respiratory chain are the result of a synergistic action of the nuclear and the mitochondrial genomes. Mutations in either or both genomes can result in a wide range of multisystemic disorders. We have studied a homoplasmic mtDNA mutation in the tRNA(Ile) gene that segregates exclusively with cardiomyopathy in two unrelated families.

A functionally dominant mitochondrial DNA mutation.

Mutations in mitochondrial DNA (mtDNA) tRNA genes can be considered functionally recessive because they result in a clinical or biochemical phenotype only when the percentage of mutant molecules exceeds a critical threshold value, in the range of 70-90%. We report a novel mtDNA mutation that contradicts this rule, since it caused a severe multisystem disorder and respiratory chain (RC) deficiency even at low levels of heteroplasmy. We studied a 13-year-old boy with clinical, radiological and biochemical evidence of a mitochondrial disorder.

Arsenic induced mitochondrial DNA damage and altered mitochondrial oxidative function: implications for genotoxic mechanisms in mammalian cells.

Arsenic is a well-established human carcinogen that is chronically consumed in drinking water by millions of people worldwide. Recent evidence has suggested that arsenic is a genotoxic carcinogen. Furthermore, we have shown that mitochondria mediate the mutagenic effects of arsenic in mammalian cells, as arsenic did not induce nuclear mutations in mitochondrial DNA (mtDNA)-depleted cells.

Biochemical analysis of respiratory function in cybrid cell lines harbouring mitochondrial DNA mutations.

We analysed key biochemical features that reflect the balance between glycolysis and glucose oxidation in cybrids (cytoplasmic hybrids) harbouring a representative sample of mitochondrial DNA point mutations and deletions. The cybrids analysed had the same 143B cell nuclear background and were isogenic for the mitochondrial background. The 143B cell line and its rho(0) counterpart were used as controls.

Copper supplementation restores cytochrome c oxidase activity in cultured cells from patients with SCO2 mutations.

Human SCO2 is a nuclear-encoded Cu-binding protein, presumed to be responsible for the insertion of Cu into the mitochondrial cytochrome c oxidase (COX) holoenzyme. Mutations in SCO2 are associated with cardioencephalomyopathy and COX deficiency. Studies in yeast and bacteria have shown that Cu supplementation can restore COX activity in cells harbouring mutations in genes involving Cu transport.