Development and hormonal control of thioredoxin and the thioredoxin-reductase system in the rat liver during the perinatal period

The development and hormonal regulation of thioredoxin and of the thioredoxin-reductase system were investigated during the perinatal period in rat liver. An immunological procedure was developed in order to quantify thioredoxin in fetal and neonatal hepatocytes. Both immunoreactive thioredoxin and thioredoxin-reductase activity appeared on day 16.5 of pregnancy. The level of immunoreactive thioredoxin increased during the late fetal period, and its level was the same 24 h after birth. Moreover, its development was not subjected to hormonal regulation by corticosteroids and glucagon. In contrast, thioredoxin-reductase activity increased 3 times during the late fetal period and presented a marked increase 24 h after birth. In the absence of glucocorticoids there was no increase in the level of thioredoxin reductase, while administration of hydrocortisone acetate and glucagon to fetuses prematurely evoked its activity. This study suggests that if thioredoxin acts physiologically, this activity is related to the state of reduction of the molecule rather than to the total concentration in the liver.     

Development and hormonal control of thioredoxin and the thioredoxin-reductase system in the rat liver during the perinatal period

Summary The development and hormonal regulation of thioredoxin and of the thioredoxin-reductase system were investigated during the perinatal period in rat liver. An immunological procedure was developed in order to quantify thioredoxin in fetal and neonatal hepatocytes. Both immunoreactive thioredoxin and thioredoxin-reductase activity appeared on day 16.5 of pregnancy. The level of immunoreactive thioredoxin increased during the late fetal period, and its level was the same 24 h after birth. Moreover, its development was not subjected to hormonal regulation by corticosteroids and glucagon. In contrast, thioredoxin-reductase activity increased 3 times during the late fetal period and presented a marked increase 24 h after birth. In the absence of glucocorticoids there was no increase in the level of thioredoxin reductase, while administration of hydrocortisone acetate and glucagon to fetuses prematurely evoked its activity. This study suggests that if thioredoxin acts physiologically, this activity is related to the state of reduction of the molecule rather than to the total concentration in the liver.     

Organophosphate-mediated inhibition of choline acetyltransferase activity in rat brain tissue

Administration of the organophosphate compound soman in rats resulted in an inhibition of choline acetyltransferase activity in almost all brain regions examined. Enzyme activity was inhibited by 20-50% in various brain regions 30 min after soman injection (94-120 micrograms/kg). Enzyme activity in two regions decreased with time to a near zero level by 3 h after injection.     

Transketolase and 2-oxoglutarate dehydrogenase activities in the brain and liver of the developing rat

Rat brain transketolase showed little change in activity from birth to adulthood, whereas the liver enzyme activity increased in a biphasic way. In both brain and liver, 2-oxoglutarate dehydrogenase activity increased gradually after birth and reached a plateau at 5 weeks of age. A developmental change in thiamin content in the brain was similar to the change in the 2-oxoglutarate dehydrogenase activity, but this was not the case in the liver.     

Transketolase and 2-oxoglutarate dehydrogenase activities in the brain and liver of the developing rat

Summary Rat brain transketolase showed little change in activity from birth to adulthood, whereas the liver enzyme activity increased in a biphasic way. In both brain and liver, 2-oxoglutarate dehydrogenase activity increased gradually after birth and reached a plateau at 5 weeks of age. A developmental change in thiamin content in the brain was similar to the change in the 2-oxoglutarate dehydrogenase activity, but this was not the case in the liver.     

Organophosphate-mediated inhibition of choline acetyltransferase activity in rat brain tissue

Summary Administration of the organophosphate compound soman in rats resulted in an inhibition of choline acetyltransferase activity in almost all brain regions examined. Enzyme activity was inhibited by 20–50% in various brain regions 30 min after soman injection (94–120 g/kg). Enzyme activity in two regions decreased with time to a near zero level by 3 h after injection.Research sponsored by the Air Force Office of Scientific Research/AFSC, United States Air Force, under Contract F49620-82-C-0035. This work was also supported by PHS MBRS Grant No. RR08037. The cooperation of Dr G. Goddard of the School of Aerospace Medicine, Brooks AFB, is gratefully acknowledged.     

Galactosyltransferase of Neurospora

Summary An enzyme, galactosyltransferase, able to catalyze the formation of galactose polymers was detected in cell-free extracts of a wild type strain of Neurospora crassa. Enzyme activity was found in both the supernatant and the particle fractions after centrifugation at 100,000 xg. The enzyme assayed in the 100,000 xg supernatant showed a 4fold difference in specific activity as compared to that found in the particle fraction.Acknowledgment. This work was supported by a grant from the Research Corporation.     

Persistance of maternally derived3H-estradiol in fetal and neonatal rats

Summary Injection of³H-estradiol into pregnant rats resulted in fetal blood radioactivity 5 times higher than in maternal blood. Significant amounts of³H-estradiol were found in fetal blood 24 h later and in the offspring 5 days after birth.Supported by NIH Grant HD 08844.     

gamma-Glutamyltranspeptidase (GGTP) and cytochrome P-450 after portacaval shunt in the rat.

The increased hepatic activity of gamma-glutamyltranspeptidase after portacaval shunt is due to derepression of a fetal enzyme rather than to an induction mechanism.     

Serum creatine kinase in marathon runners

Serum creatine phosphokinase (CK) and CK-MB activity were determined in 21 trained runners participating in a marathon race (42.2 km). Enzyme activities immediately after the race increased two to three times compared with activities before the race. The greatest increases were found in the slowest runners, suggesting greater skeletal muscular trauma in the least trained or fit. As these are likely to include the older athletes who are also more likely to suffer acute myocardial injury during strenuous exercise, our findings assume special import in the interpretation of increased CK and CK-MB serum activities of older athletes.     

Galactosyltransferase of Neurospora.

An enzyme, galactosyltransferase, able to catalyze the formation of galactose polymers was detected in cell-free extracts of a wild type strain of Neurospora crassa. Enzyme activity was found in both the supernatant and the particle fractions after centrifugation at 100,000 X g. The enzyme assayed in the 100,000 X g supernatant showed a 4fold difference in specific activity as compared to that found in the particle fraction.     

Endocrine control of lysosomal alterations in rat liver during the perinatal period

Within hours of birth, some physical properties of liver lysosomes are modified. These alterations, which may be related to the autophagic vacuoles formation known to occur during this period, were inhibited by insulin administration. Glucagon, a potent inducer of autophagy in adult rat liver, did not anticipate this process in fetal liver. Our results suggest that the decrease of plasma insulin immediately after birth is an important factor in the development of hepatic autophagy.     

Increased ALA dehydratase activity and spleen weight in lead-intoxicated rats. A consequence of increased blood cell destruction

Lead was given in the diet (1%) to rats from birth and at different times the animals were studies for delta amino levulinic acid dehydratase (ALAD) activity, spleen weight, 59Fe incorporation in erythrocytes and 51Cr-labeled erythrocytes survival. The increased ALAD and spleen weight found after lead treatment is explained as a consequence of a shortened survival, which results in a younger age of circulating erythrocytes with higher ALAD activity.     

Endocrine control of lysosomal alterations in rat liver during the perinatal period

Summary Within hours of birth, some physical properties of liver lysosomes are modified. These alterations, which may be related to the autophagic vacuoles formation known to occur during this period, were inhibited by insulin administration. Glucagon, a potent inducer of autophagy in adult rat liver, did not anticipate this process in fetal liver. Our results suggest that the decrease of plasma insulin immediately after birth is a important factor in the development of hepatic autophagy.     

Serum creatine kinase in marathon runners

Summary Serum creatine phosphokinase (CK) and CK-MB activity were determined in 21 trained runners participating in a marathon race (42.2 km). Enzyme activities immediately after the race increased two to three times compared with activities before the race. The greatest increases were found in the slowest runners, suggesting greater skeletal muscular trauma in the least trained or fit. As these are likely to include the older athletes who are also more likely to suffer acute myocardial injury during strenuous exercise, our findings assume special import in the interpretation of increased CK and CK-MB serum activities of older athletes.Acknowledgments. The authors wish to thank the members and president of the Columbia Track Club for their cooperation.     

Comparative ontogenesis of gamma-glutamyl transpeptidase in rat tissues

Summary In rats, placental gamma glutamyl transpeptidase (GGTP) specific activity declined linearly during the last third of gestation. In contrast, the kidney enzyme activity progressively increased 15-fold. In the gut, peak activity was reached at mid-lactation (age 12 days). Hepatic GGTP levels were maximal during the foetal stage. Brain GGTP was negligible at birth and attained its highest specific activity at weaning.This work was supported in part by USPHS NIH SO8 RR-09128-03.     

Administration of D-alanine did not cause increase of D-amino acid oxidase activity in mice.

D-amino acid oxidase (DAAO) activity was not altered in the liver and kidney by oral administration of D-alanine to adult mice. The enzyme was apparently not induced by the enteric microflora either, since the enzyme activity in the liver and kidney of germ-free mice was not different from that of specific-pathogen-free mice. The times of appearance of DAAO activity and of free D-amino acids in the kidney were elucidated using suckling mice. DAAO activity started to increase 7 days after birth, and reached almost the adult level by 28 days. The content of free neutral D-amino acids also increased with age, in a similar fashion. A possible conclusion is that the enzyme activity normally increases during this period, to eliminate the free D-amino acids which have increased with age in the suckling mice. Consequently, the administration of D-alanine had no further effect in increasing enzyme activity.     

Administration of D-alanine did not cause increase of D-amino acid oxidase activity in mice

D-amino acid oxidase (DAAO) activity was not altered in the liver and kidney by oral administration of D-alanine to adult mice. The enzyme was apparently not induced by the enteric microflora either, since the enzyme activity in the liver and kidney of germ-free mice was not different from that of specific-pathogen-free mice. The times of appearance of DAAO activity and of free D-amino acids in the kidney were elucidated using suckling mice. DAAO activity started to increase 7 days after birth, and reached almost the adult level by 28 days. The content of free neutral D-amino acids also increased with age, in a similar fashion. A possible conclusion is that the enzyme activity normally increases during this period, to eliminate the free D-amino acids which have increased with age in the suckling mice. Consequently, the administration of D-alanine had no further effect in increasing enzyme activity.     

Establishment of intestinal homeostasis during the neonatal period

The intestinal mucosa faces the challenge of regulating the balance between immune tolerance towards commensal bacteria, environmental stimuli and food antigens on the one hand, and induction of efficient immune responses against invading pathogens on the other hand. This regulatory task is of critical importance to prevent inappropriate immune activation that may otherwise lead to chronic inflammation, tissue disruption and organ dysfunction. The most striking example for the efficacy of the adaptive nature of the intestinal mucosa is birth. Whereas the body surfaces are protected from environmental and microbial exposure during fetal life, bacterial colonization and contact with potent immunostimulatory substances start immediately after birth. In the present review, we summarize the current knowledge on the mechanisms underlying the transition of the intestinal mucosa during the neonatal period leading to the establishment of a stable, life-long host–microbial homeostasis. The environmental exposure and microbial colonization during the neonatal period, and also the influence of maternal milk on the immune protection of the mucosa and the role of antimicrobial peptides, are described. We further highlight the molecular mechanisms of innate immune tolerance in neonatal intestinal epithelium. Finally, we link the described immunoregulatory mechanisms to the increased susceptibility to inflammatory and infectious diseases during the neonatal period.     

Postnatal decline of (Ca2+ + Mg2+)-activated membrane ATPase in cattle red cells.

Acitivity of membrane bound (Ca2+ + Mg2+)-stimulated ATPase, associated with Ca2+ outward transport, in calf red cells is high at birth and declines with a rate constant of 0.041 d-1 after the 3rd week. The decline parallels the disappearance of fetal hemoglobin.