Coenzyme Q10 and its putative role in the ageing process

Summary A phenomenon associated with the aging process is a general age-dependent decline in cellular bioenergetic capacity that varies from tissue to tissue and even from cell to cell within the same tissue. This variation eventually forms a tissue bioenergy mosaic. Recent evidence by our group suggests that the accumulation of mitochondrial DNA mutations, in conjunction with a concurrent decrease in full-length mtDNA in tissues such as skeletal and cardiac muscle, strongly correlates with decreased mitochondrial function and accounts for the bioenergy mosaic. Evidence is also presented suggesting that amelioration with coenzyme Q₁₀ may restore some of the age-associated decline in bioenergy function, in effect providing the potential for a “redox therapy”. Coenzyme Q is a naturally occurring material that is present in the membranes of all animal cells. Its primary function is to act as an electron carrier in the mitochondrial electron transport chain enabling the energy from substrates such as fats and sugars (in the form of reducing equivalents) to be ultimately captured in the form of ATP, which in turn may be utilised as a source of cellular bioenergy. Coenzyme Q₁₀ has no known toxic effects and has been used in a limited number of animal studies and human clinical trials; however, the mechanism of action of coenzyme Q₁₀ remains unclear. A series of experiments by this group aimed at determining the efficacy of coenzyme Q₁₀ treatment on ameliorating the bioenergy capacity at the organ and cellular level will also be reviewed.     

Gene silencing of mannose 6-phosphate reductase in the parasitic weed Orobanche aegyptiaca through the production of homologous dsRNA sequences in the host plant

Orobanche spp. (broomrape) are parasitic plants which subsist on the roots of a wide range of hosts, including tomato, causing severe losses in yield quality and quantity. Large amounts of mannitol accumulate in this parasitic weed during development. Mannose 6-phosphate reductase (M6PR) is a key enzyme in mannitol biosynthesis, and it has been suggested that mannitol accumulation may be very important for Orobanche development. Therefore, the Orobanche M6PR gene is a potential target for efforts to control this parasite. Transgenic tomato plants were produced bearing a gene construct containing a specific 277-bp fragment from Orobanche aegyptiaca M6PR-mRNA, in an inverted-repeat configuration. M6PR-siRNA was detected in three independent transgenic tomato lines in the R1 generation, but was not detected in the parasite. Quantitative RT-PCR analysis showed that the amount of endogenous M6PR mRNA in the tubercles and underground shoots of O. aegyptiaca grown on transgenic host plants was reduced by 60%–80%. Concomitant with M6PR mRNA suppression, there was a significant decrease in mannitol level and a significant increase in the percentage of dead O. aegyptiaca tubercles on the transgenic host plants. The detection of mir390, which is involved with cytoplasmic dsRNA processing, is the first indication of the existence of gene-silencing mechanisms in Orobanche spp. Gene silencing mechanisms are probably involved with the production of decreased levels of M6PR mRNA in the parasites grown on the transformed tomato lines.     

Neonatal injury rapidly alters markers of pain and stress in rat pups

Less than 60% of infants undergoing invasive procedures in the neonatal intensive care unit receive analgesic therapy. These infants show long‐term decreases in pain sensitivity and cortisol reactivity. In rats, we have previously shown that inflammatory pain experienced on the day of birth significantly decreases adult somatosensory thresholds and responses to anxiety‐ and stress‐provoking stimuli. These long‐term changes in pain and stress responsiveness are accompanied by two‐fold increases in central met‐enkephalin and β‐endorphin expression. However, the time course over which these changes in central opioid peptide expression occur, relative to the time of injury, are not known. The present studies were conducted to determine whether the observed changes in adult opioid peptide expression were present within the first postnatal week following injury. The impact of neonatal inflammation on plasma corticosterone, a marker for stress reactivity, was also determined. Brain, spinal cord, and trunk blood were harvested at 24 h, 48 h, and 7 d following intraplantar administration of the inflammatory agent carrageenan on the day of birth. Radioimmunoassay was used to determine plasma corticosterone and met‐enkephalin and β‐endorphin levels within the forebrain, cortex, midbrain, and spinal cord. Within 24 h of injury, met‐enkephalin levels were significantly increased in the midbrain, but decreased in the spinal cord and cortex; forebrain β‐endorphin levels were significantly increased as a result of early life pain. Corticosterone levels were also significantly increased. At 7 d post‐injury, opioid peptides remained elevated relative to controls, suggesting a time point by which injury‐induced changes become programmed and permanent. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 42–51, 2014