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Biomedical subjects

C A Lang

Publications and source records attributed to C A Lang.

66 records · Page 4Linked to original sources
PubMed1967

Nicotinamide-adenine dinucleotide phosphate enzymes in the mosquito during growth and aging.

1. Optimum conditions were established for determining the activities of the NADP(+)-linked enzymes, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and isocitrate dehydrogenase, in mosquito tissues. 2. The activity of each dehydrogenase was determined in samples of mosquitoes of different ages throughout the life-span. The specific-activity curves attained maximal values in the pupal or early adult period. From these maxima an 81% decrease in glucose 6-phosphate-dehydrogenase and 67% decrease in 6-phosphogluconate-dehydrogenase activities occurred after the tenth day of adult life; a 77% decrease in isocitrate-dehydrogenase activity occurred before the fifth day. 3. The activity differences were found in different body regions as well as in whole organisms. 4. Starvation of the larva or adult did not result in decreases in enzyme activity. 5. These findings support the hypothesis that the activities of enzymes that form NADPH are related to the biosynthetic activity, for the enzyme activities increased during the period of cellular growth and decreased during the aging period.

Abdomen↗
PubMed1966

Nicotinamide-adenine dinucleotide pyrophosphatase in the growing and aging mosquito.

1. The disappearance of pyridine nucleotides during incubation with mosquito homogenates proceeds through the hydrolysis of the pyrophosphate linkage of these compounds as demonstrated by the formation of NMN and AMP from NAD(+). This reaction was also demonstrated by the loss in the coenzyme functioning property of NAD(+) (yeast alcohol dehydrogenase reaction) without a concomitant loss in reactivity towards cyanide. Transglycosidase activity was not observed in the mosquito homogenates, and low concentrations of nicotinamide did not inhibit the NAD(+) splitting activity of these homogenates. These observations are all in accord with the presence in these homogenates of a NAD(+) pyrophosphatase rather than a NADase. 2. The NAD(+) pyrophosphatase is destroyed by boiling, is not heat-activated, and has a pH optimum at pH8.75. In addition to NAD(+), other dinucleotides such as NADP(+), the 3-acetylpyridine and thionicotinamide analogues of NAD(+) and the thionicotinamide analogue of NADP(+), function as substrates in the hydrolysis catalysed by the pyrophosphatase. 3. A decrease in the specific activity of NAD(+) pyrophosphatase was observed during larval development, and a barely detectable activity was found in the pupa and adult. 4. Enzyme activity per organism increased in the larva but decreased to a very low value in the pupa and adult. These results indicate that the decrease in specific activity was due to a decrease in enzyme concentration rather than an increase in amounts of protein.

Adenine Nucleotides↗
PubMedDate not supplied

Life span profiles of glutathione and acetaminophen detoxification.

Our previous finding of a glutathione (GSH) deficiency in aging or senescent mice suggested that a concomitant decrease in detoxification capacity also may occur. To test this, mice at different biological stages of the life span (growth, maturity, aging or senescence) were injected with various doses of acetaminophen (APAP), and GSH depletion and recovery rates were determined. At intervals for 24 hr, samples of blood and other tissues were obtained, processed, and analyzed for reduced GSH, glutathione disulfide (GSSG), cysteine, and cystine using HPLC with dual electrochemical detection. In the uninjected controls, the GSH concentration decreased about 30% in all tissues of the aging mouse, but the GSSG cysteine, and cystine levels were unchanged during the life span. APAP administration depleted liver and lung GSH contents in a dose- and time-dependent manner. Four hr after APAP administration, hepatic GSH levels of all ages had decreased 70-80%. After 24 hr, the GSH levels of the young, growing (3-6 months), and mature (12 months) mice recovered to 94 and 66%, respectively, of the controls. In contrast, the level in aging (31 months) mice rose only 41%, a lower recovery that was correlated with their decreased GSH content. The lungs of old mice also were GSH-deficient but differed from liver, for there was less GSH depletion by APAP and no decrease in GSH recovery. Thus, these findings demonstrate clearly the occurrence of decreased detoxification capacity in the GSH-deficient, aging mouse.

Acetaminophen↗
PubMedDate not supplied

Aging effects on acetaminophen toxicity and glutathione status in the mosquito.

Previously we found that a decrease in glutathione (GSH) concentration is a general phenomenon in aging organisms. This suggested our hypothesis that the capacity for detoxification involving GSH will decrease in senescence. Thus the present objectives were to determine the toxicity of acetaminophen (APAP) and its relationship to GSH status in the aging mosquito. Different concentrations of APAP in Aedes Ringer were injected into adult mosquitoes of different ages through the life-span. The results showed that the LD50 values were highest in the young adult, plateaued in the mature, and decreased 7-fold in the very old adults (p less than 0.0001). Of special interest was that these decreasing LD50 values were closely correlated with the aging-specific decreases in GSH concentration observed in our previous experiments (r = 0.99). Also a direct relationship was established as the administration of a lethal dose (LD50) of APAP depleted more than 99% of the GSH content (p less than 0.0001). This is the first demonstration of an aging-specific decrease in detoxification capacity in a well characterized aging model. Further, these findings suggest that GSH levels may serve as an indicator of vulnerability to other toxicants.

Acetaminophen↗