Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytosolic Ca2+ overload may play a key role in the process of lead-induced retinal injury and degeneration. We report that retinal calcium content was elevated following developmental and in vitro lead exposure. To determine the concentration-dependent effects of Ca2+ (5-1000 nM) on retinal mitochondrial bioenergetics an isolation procedure was developed. Isolated mitochondria were efficiently coupled; had good respiratory control ratios with the NAD-linked substrates, glutamate or pyruvate plus malate (G/M or P/M), and the FAD-linked substrate, succinate plus rotenone (S/R); and possessed a Na+/Ca2+ exchanger. The major finding was that at equimolar [Ca2+] > or = 35 nM, mitochondria were more sensitive to and exhibited a greater degree of inhibition of coupled and uncoupled respiration with NAD-linked substrates compared to S/R. At all [Ca2+], decreases in State 3 and uncoupled respiration were similar, thereby eliminating the ATP synthase and ADP/ATP translocase as sites of inhibition and suggesting that opening the mitochondrial permeability transition pore (MTP) did not contribute to the inhibition. The effects of toxicological [Ca2+] were: (1) blocked by ruthenium red, (2) blocked by dibucaine only in the presence of NAD-linked substrates, and (3) partially reversed by NAD+ with G/M after opening the MTP. Results with G/M suggest that Ca2+ acts on the inner membrane phospholipase A2 to decrease NADH CoQ reductase activity and/or produce a NAD+ leak, whereas with S/R, Ca2+ may inhibit succinate dehydrogenase. In conclusion, Ca2+ inhibits retinal mitochondrial ATP production, which may contribute to the retinal cell injury and death observed in developmentally lead-exposed rats.
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PMID:Substrate-dependent effects of calcium on rat retinal mitochondrial respiration: physiological and toxicological studies. 817 38

1. Winter survival for numerous cold-blooded animals includes freeze tolerance: the ability to endure the conversion of as much as 65% of total body water into extracellular ice. Selected molecular adaptations underlying freeze tolerance (e.g. cryoprotectants, ice nucleating proteins) have been widely studied, but the full range of metabolic adjustments needed for freeze endurance remains unknown. 2. Recent studies using gene screening techniques are providing a different approach to the search for biochemical responses that support freezing survival by identifying genes and proteins that are up-regulated by freezing or thawing in freeze-tolerant amphibians and reptiles. 3. Screening of a cDNA library from wood frog liver revealed the freeze-induced up-regulation of genes coding for the alpha- and gamma-subunits of fibrinogen (a plasma clotting protein), the mitochondrial ADP/ATP translocase and a novel 10 kDa protein containing a nuclear exporting sequence. 4. Northern blotting revealed that these genes were differentially responsive to two of the component stresses of freezing (dehydration and anoxia), indicating that different genes are induced by signals radiating either from cell volume change or oxygen deprivation during freezing. 5. Freeze up-regulation of fibrinogen synthesis in liver and other organs appears to be a damage repair response that anticipates a need for enhanced plasma clotting capacity to deal with ice crystal damage to capillary beds. 6. Up-regulation of ADP/ATP translocase in frog liver is linked with ischaemia resistance and studies with freeze-tolerant turtles have shown that other genes encoding proteins involved in mitochondrial energetics (NADH-ubiquinone oxido-reductase subunit 5, cytochrome C oxidase subunit 1) are also up-regulated by both anoxia and freezing exposures. 7. These studies are making major advances in our understanding of freeze tolerance as a natural phenomenon and also highlight new key areas that can be targeted by applied interventions for the optimization of medical cryopreservation techniques for cells, tissues and organs.
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PMID:Living in the cold: freeze-induced gene responses in freeze-tolerant vertebrates. 1002 71