Tannic acid, a higher galloylated pentagalloylglucose, suppresses antigen-specific IgE production by inhibiting ɛ germline transcription induced by STAT6 activation.

Interleukin (IL)-4 is a critical stimulator that induces ɛ germline transcripts (ɛGT) for switch recombination to initiate immunoglobulin (Ig) E and is important in allergic disease pathogenesis. We found pentagalloylglucose (PGG) inhibited IL-4-induced ɛGT expression. PGG exerted its inhibitory function by suppressing IL-4-induced activation of IL-4Rα, JAK3 and STAT6. Furthermore, tannic acid, a higher galloylated PGG, attenuated ovalbumin-induced IgE production in vivo by inhibiting IL-4-induced ɛGT expression and the IL-4 signaling pathway. In conclusion, our results suggest that tannic acid may attenuate allergic diseases by suppressing IgE production by inhibiting IL-4-induced signaling.

Contents of all forms of vitamin B6, pyridoxine-ß-glucoside and 4-pyridoxic acid in mature milk of Japanese women according to 4-pyridoxolactone-conversion high performance liquid chromatography.

The contents of six vitamin B6 forms, pyridoxine-ß-glucoside, and 4-pyridoxic acid in mature milk of 20 Japanese lactating women consuming ordinary Japanese foods were determined by a 4-pyridoxolactone-conversion HPLC method. These compounds were determined with the average recovery rate of 83.9% or more. The average total content of vitamin B6 forms was 1.01 ± 0.32 (µmol/L). Pyridoxal and pyridoxal 5'-phosphate were found in all of the samples, and their average contents were 0.71 ± 0.28 (µmol/L) and 0.16 ± 0.07 (µmol/L), respectively. Pyridoxamine, pyridoxine, pyridoxamine 5'-phosphate, pyridoxine 5'-phosphate, and pyridoxine-ß-glucoside were found in 15, 14, 13, 9, and 7 samples, respectively. The presence of pyridoxine 5'-phosphate was for the first time found in human milk. A method for the determination of 4-pyridoxic acid, which is the excretion form of vitamin B6, was modified to quantitate it by isocratic HPLC. 4-Pyridoxic acid was found in all samples, and its average content was 0.094 ± 0.040 (µmol/L), which was only 12% of its content in cow (Holstein) milk. The total content of vitamin B6 forms, and predominant presence of pyridoxal among other vitamin B6 forms in the Japanese women's milk samples shared similar characteristics with American women's milk samples.

Activity of prolidase isoenzymes in the rat brain: subcellular and regional distribution during development.

Prolidase deficiency is characterized by chronic ulcerative dermatitis, mental retardation, and frequent infections. In the present study we examined the characteristics of rat brain prolidase isoenzymes. Prolidase isoenzymes (PD I and PD II) were isolated from the rat brain using DEAE cellulose column chromatography. PD I showed higher activity against seryl-proline and alanyl-proline, while PD II was particularly active against methionyl-proline. Prolidase activity in the whole brain and in the different brain regions showed higher activity against methionyl-proline and seryl-proline. PD II activity was highest in the hippocampus, followed by the cerebellum, cerebral cortex, caudatum, and the midbrain. The most rapid changes in the activities of PD I and PD II occurred perinatally, with a peak at three days before birth and a nadir at two days after birth, which then gradually increased until 21 days. N-benzyloxycarbonyl-l-proline inhibited PD I activity against various substrates in a dose-dependent manner. In contrast, there was no inhibition of PD II activity against methionyl-proline at low concentrations. In summary, these data suggest that maintenance of levels of proline, other amino acids and peptides containing proline in the rat brain is regulated by prolidase isoenzymes. The age-related alterations in PD I and PD II also may help to elucidate the fundation of prolidase isoenzymes in brain nervous system.

Prolidase isoenzymes in the rat: their organ distribution, developmental change and specific inhibitors.

Lack of prolidase I (PD I) leads to prolidase deficiency, a disease characterized by intractable skin lesions, recurrent respiratory infections, and mental retardation. The present study was undertaken to characterize and determine the physiologic roles of different prolidase isoenzymes. Two isoforms of prolidase were isolated from rat kidney. PD I showed higher activity against seryl-proline and alanyl-proline, whereas PD II was active especially against methionyl-proline. PD I was highly concentrated in the small intestine and kidney, whereas PD II was shown not to vary in the organs examined. Expression of PD I and PD II in the small intestine were maximal within 1 wk of birth, and then rapidly declined. The changes of prolidase in the kidney and heart were found to differ slightly. N-benzyloxycarbonyl-l-proline and captopril inhibited PD I dose-dependently, but showed no inhibition of PD II at low concentrations. NiCl2 inhibited PD II much more effectively than PD I. Our findings suggest that PD I functions by way of an intestinal peptide carrier, which may also be regulated by the uptake of various iminodipeptides. Similarly, age-related alterations of prolidase isoenzymes suggest that intestinal PD II also participates in absorption of proline and other amino acids early in life.

Different effects of sulfur amino acids on prolidase and prolinase activity in normal and prolidase-deficient human erythrocytes.

BACKGROUND: Prolidase and prolinase activity is known to be enhanced significantly in some diseases. Recently, the effect of amino acids on prolidase and prolinase activity in normal and prolidase-deficient human erythrocytes was investigated. It was reported that both enzymes were enhanced by glycine and alanine in the presence of MnCl(2). METHODS: Erythrocytes were isolated from heparinized blood from normal human and a patient with prolidase deficiency. Effects of various sulfur amino acids on prolidase and prolinase activities against iminodipeptides in the presence of 1 or 0.1 mmol/l MnCl(2) were investigated. RESULTS: Prolinase activity against prolylglycine in normal and prolidase-deficient erythrocyte lysates was inhibited by L-methionine, NAc-L-methionine and D,L-methionine in a concentration-dependent manner, but D-methionine enhanced the activity in low concentrations (0-20 mmol/l). D,L-Homocysteine inhibited the activity more strongly than other sulfur amino acids tested in a concentration-dependent manner. On the other hand, prolidase activity against glycylproline was enhanced by L-methionine, D-methionine, D,L-methionine, D,L-homocysteine thiolactone and D,L-ethionine. The rates of enhancement by these sulfur amino acids were in the following order: D,L-ethionine>D,L-methionine, D-methionine, D,L-homocysteine thiolactone>L-methionine (10 mmol/l). CONCLUSION: The prolinase activity in normal and prolidase-deficient erythrocyte lysates was inhibited by L-methionine, D,L-ethionine and D,L-homocysteine. On the other hand, prolidase activity in their erythrocyte lysates was enhanced by D,L-ethionine, D-methionine and L-methionine. These results indicate the effects of these sulfur amino acids on prolidase and prolinase activities were different.

Characterization of prolidase activity in erythrocytes from a patient with prolidase deficiency: comparison with prolidase I and II purified from normal human erythrocytes.

OBJECTIVES: The purpose of this study was to investigate the effect of various amino acids and their metabolites on the activities of prolidase I and II from human erythrocytes compared to those in a patient with prolidase deficiency. DESIGN AND METHODS: Prolidase I and II from human erythrocytes were purified by using column chromatography. Prolidase activity against various iminodipeptides was determined by spectrophotometry using Chinard's method. RESULTS: The activities of prolidase I and II against glycylproline and methionylproline were enhanced by glycine, L- and D-isoforms of alanine and serine and D-isoforms of valine, leucine and isoleucine. L-isoforms of branched amino acids inhibited the activity of prolidase I. On the other hand, the activity of prolidase II was enhanced by all of these L-branched amino acids. The patient's prolidase activity was also enhanced by all the L- and D-branched amino acids. CONCLUSION: The activities of prolidase I and II against various iminodipeptides were prominently enhanced by glycine, but the effect of L-valine differed between the two enzymes. Enzymatic properties of the patient's prolidase were essentially the same as those of prolidase II.

Effects of amino acids and its metabolites on prolidase activity against various iminodipeptides in erythrocytes from normal human and a patient with prolidase deficiency.

BACKGROUND: The characteristics of prolidase in erythrocytes from controls and patient with prolidase deficiency were investigated. METHODS: The erythrocytes were isolated from the heparinized blood of normal human and a patient with prolidase deficiency. Effects of various amino acids and their metabolites on prolidase activity against iminodipeptides in presence of 1 mmol/l MnCl(2) were investigated. RESULTS: Prolidase activity against glycylproline in erythrocytes from normal human was strongly enhanced by glycine, L-alanine, L-serine with MnCl(2), but the activity was strongly inhibited by L-valine, and L-leucine. However, the stereoisomers, D-leucine and D-valine enhanced the activity. The prolidase activity against methionylproline in erythrocytes from the patient with prolidase deficiency was also enhanced by glycine, L-alanine and L-serine. The activity was inhibited by l-leucine, but D-leucine and L-valine enhanced the activity against various iminodipeptides. CONCLUSION: Prolidase activity against glycylproline in normal human erythrocytes and against methionylproline from the prolidase-deficient patient was enhanced strongly by glycine, alanine and serine with MnCl(2). However, this activity was inhibited by L-leucine, but was enhanced by D-leucine.

Characteristics of prolidase from the erythrocytes of normal humans and patients with prolidase deficiency and their mother.

Prolidases I and II were highly purified from human erythrocytes. The effects of various amino acids, MnCl2 and mercaptoethanol, on these two enzymes were investigated. Normal prolidase II was very labile in the absence of MnCl2 or mercaptoethanol. The activity of prolidase II was maintained at about 76% by pre-incubation with MnCl2; it was then activated up to 140% by treatment with mercaptoethanol for 60 minutes at 37 degrees C. Normal prolidases I and II showed the highest activity against glycylproline or methionylproline in the presence of MnCl2. The activity of prolidase I against glycylproline was enhanced strongly by glycine and MnCl2, but not activated in the absence of MnCl2. The activity of prolidase II against methionylproline was enhanced three-fold in the presence of glycine and MnCl2, but its activity against glycylproline was very low even in the presence of MnCl2. A stronger enhancement of this activity was found in normal erythrocytes, and a lower level of this activity was found in erythrocytes of patients treated with glycine, MnCl2 and mercaptoethanol compared to those treated with glycine and MnCl2. The activity of prolidase II against methionylproline in all erythrocytes, of normal humans and of patients, was strongly activated by the addition of glycine with MnCl2 but suppressed by the addition of mercaptoethanol.