Detoxification Mechanism in the Rat Extraorbital Lacrimal Gland: Conjugation of Brefeldin A to Glutathione

In this work the existence of a glutathione based detoxification system in rat lacrimal glands is reported. We showed that brefeldin A, a drug used as a tool for the study of intracellular trafficking mechanisms, was inactivated by metabolization and converted into two derivatives. We purified them by high performance liquid chromatography and determined, by mass spectroscopy, that they correspond to glutathione and cysteine derivatives of BFA. The determination of the respective amounts of these derivatives in the medium and the tissue in different experimental conditions, revealed that glutathione-BFA is formed in the tissue, excreted from the cells, cleaved by γ-glutamyl transpeptidase and finally converted to cysteine-BFA.     

Properties of γ-Glutamyl Transpeptidase in Squamous Cell Carcinoma

γ-Glutamyl transpeptidase (GGT) was extracted from squamous cell carcinoma tissues of human skin (SCC) by Triton X-100 and bromelain treatment, and some of its biochemical properties were compared with those of GGT extracted from eccrine gland-rich tissue and normal kidney. GGT activity significantly increased in SCC, but there was no definitive differences in enzymological properties between GGT of SCC and normal tissue enzyme. However, GGT of SCC was distinguishable from those of normal tissues by isoelectric point, electrophoretic mobility, and sensitivity to neuraminidase treatment. These results indicate that GGT of SCC has some variant properties which may be related to skin carcinogenesis.     

Enzyme-altered Liver Cell Foci in Woodchucks Infected with Woodchuck Hepatitis Virus

The histochemical characteristics of liver cell foci in woodchucks were investigated. The foci appeared to be distributed throughout the liver and were observed only in the woodchuck hepatitis virus (WHV)-positive animals, including all 19 woodchucks with hepatocellular carcinoma(HCC), and 7 without HCC. No foci appeared in 11 WHV-negative animals. Histochemical studies revealed that liver cell foci and carcinoma cells were characterized by positive gamma-glutamyl transpeptidase (GGT) enzymatic reactions and decreased glucose-6-phosphatase enzyme activity compared to non-neoplastic liver. Furthermore, serum GGT was significantly elevated in almost all of the animals which had larger carcinomas. Ultrastructural findings of foci showed some resemblance to carcinoma cells, being characterized by abundant free ribosomes within the cytoplasm and undeveloped endoplasmic reticulum. These results suggest that the liver cell foci are potential precursors of HCC in WHV-infected animals, and that serum GGT may be a useful marker for indicating the development of carcinoma.     

Effects of L-glutamine on tyrosinase and gamma-glutamyl transpeptidase of B-16 melanoma cells in culture

Omission of L-glutamine (Gln) from the culture medium decreases tyrosinase activity and increases γ-GTP activity in cultured melanotic B-16 melanoma cells; inclusion of this amino acid in the medium shows the reverse effects. Its absence, however, decreases the γ-GTP activity in non-pigmented cells like HeLa cells, fibroblasts and amelanotic melanoma cells and its presence induces a dose dependent increase in this enzyme activity in these cells. The decrease of γ-GTP activity in the melanotic melanoma cells by Gln is attributed to increased production of dopa and its derivatives by these cells, as evidenced by our results. Our data also indicate the inhibitory effects of dopa and several other dopa derivatives known to be produced by the melanoma cells on isolated bovine kidney γ-GTP.     

Transient elevation of hepatic enzymes in volunteers after intake of alcohol

BACKGROUND: In the organs that mediate alcohol effects on the human body and its health, the liver plays a particular important role. This study was designed to detect the changes of hepatic enzymes after alcohol intake and evaluate the corresponding damage to the human body. METHODS: Fifteen volunteers were included according to the criteria. After the intake of 80g ethanol containing beverage, alcohol levels were detected and blood samples were collected at 0.5-to 3-hour interval to detect the levels of hepatic enzymes simultaneously. RESULTS: After the intake of 80g ethanol, various symptoms occurred in volunteers while the concentration of blood alcohol peaked at 1 hour and normalized within 24 hours. The ratio of alanine aminotransferase (ALT) to aspartate aminotransferase (AST) increased significantly when the venous alcoholic concentration increased from 0g/L to 1.2g/L and the levels of alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase(γ-GT) were elevated when the alcoholic concentration reached 0.4g/L. No significant changes were noticed in ALT, AST or cholinesterase (CHE). CONCLUSION: Acute alcohol intoxication may cause the changes of hepatic enzymes and prove the existence of reversible hepatic injury.     

Might hyperthyroxinemic states exacerbate bronchial asthma by stimulating the production of leukotrienes C4, D4 or E4?

Thyrotoxicosis is known to exacerbate bronchial asthma. Leukotrienes C₄, D₄ and E₄ have the capacity to constrict airway smooth muscle and impair pulmonary compliance. A rationale is hereby suggested whereby thyroid hormones are implicated in the synthesis of leukotrienes C₄, D₄ and E₄.     

SERUM GAMMA-GLUTAMYL TRANSPEPTIDASE ACTIVITY AND URINARY D-GLUCARIC ACID EXCRETION IN NEWBORNS IN THE FIRST WEEK OF LIFE; Effects of phenobarbital and nicethamide combination

ABSTRACT. High serum γ-glutamyl transpeptidase activity was found in cord blood of newborn boys. This activity decreased to lower values on the 4th and 7th days. In newborns treated for 3 days following the birth with a combination of Phenobarbital and nicethamide an increase of γ-glutamyl transpeptidase activity occurred from the 4th to the 7th days. The 7th day levels were significantly higher when compared with the controls. Simultaneous determination of urinary glucaric acid excretion confirmed the induction of hepatic microsomal enzymes in glucuronic acid pathway. This could also be demonstrated by a pronounced decrease of serum bilirubin levels in groups receiving the enzyme inducers whether phenobarbital was administered intramuscularly or orally as sodium salt solution.     

丹参、肌苷对犬热缺血肾γ——GT.LAP活性的影响

给犬(每组10条)静脉注射丹参(1g/kg)或肌苷(50mg/kg),钳夹左肾动脉60分钟后重新开放肾血流,丹参组和肌苷组缺血肾尿γ-GT、LAP活性明显低于对照组,丹参组与肌苷组之间则无明显差异。左肾缺血对血清和右肾尿γ-GT、LAP活性没有明显影响。本文对实验结果作了讨论。     

Polarity of the blood-brain barrier: Distribution of enzymes between the luminal and antiluminal membranes of brain capillary endothelial cells

The subcellular distribution in brain capillaries of alkaline phosphatase and Na+, K+-ATPase was investigated by two methods. Cytochemical studies using whole brain perfusion and electron microscopic examination indicated that alkaline phosphatase activity was located in both the luminal and antiluminal cytoplasmic membranes of the brain capillary endothelial cells. By contrast, the K+-dependent phosphatase activity associated with Na+, K+-ATPase was located in only the antiluminal membrane. Biochemical studies using membranes prepared by homogenization of isolated brain capillaries and density gradient centrifugation resulted in identification of two plasma membrane fractions. The light fraction contained alkaline phosphatase but very little Na+, K+-ATPase while the heavier fraction contained both enzyme activities. In addition, gamma-glutamyl transpeptidase showed a distribution similar to alkaline phosphatase while 5'-nucleotidase activity was distributed with the Na+, K+-ATPase activity. We conclude that the luminal and antiluminal membranes of brain capillaries are biochemically and functionally different. This polarity should permit active solute transport across brain capillary endothelial cells which are the cells responsible for the blood-brain barrier.     

Might hyperthyroxinemic states exacerbate bronchial asthma by stimulating the production of leukotrienes C4, D4 or E4?

Thyrotoxicosis is known to exacerbate bronchial asthma. Leukotrienes C₄, D₄ and E₄ have the capacity to constrict airway smooth muscle and impair pulmonary compliance. A rationale is hereby suggested whereby thyroid hormones are implicated in the synthesis of leukotrienes C₄, D₄ and E₄.