Tryptophan과 imipramine처리가 흰쥐의 중뇌 솔기핵의 serotonin 면역반응 신경 세포체에 미치는 영향

김명순(Myoung-Soon Kim),이창현(Chang-Hyun Lee) 대한해부학회 2002 Anatomy & Cell Biology Vol.35 No.1

필수 아미노산인 tryptophan과 imipramine을 흰쥐의 복강에 장기간 (20일) 투여한 후 중뇌 솔기핵의 신경 세포체의 수와염색강도를 면역조직화학 염색법에 의하여 관찰한 바 다음과 같은 결과를 얻었다. 1) Tryptophan을 투여한 군에서는 imipramine을 투여한 군에 비해 serotonin에 면역반응을 보인 신경 세포체의 수가 유 의성있게 증가함을 알 수 있었다. 2) Imipramine을 투여한 군에서는 saline 투여군에 비해 serotonin에 대한 면역 반응을 보인 신경 세포체의 수가 감소 되었다. 3) Tryptophan-imipramine 투여군에서는 tryptophan을 투여한 군보다 serotonin에 면역 반응을 보인 신경 세포체의 수가 감소하였으나 imipramine 투여군에 비하여 serotonin에 면역반응을 보인 신경 세포체의 수는 유의성있게 증가 하였다. 이상의 실험결과로 tryptophan 투여시 전전구물질인 tryptophan의 축적으로 인하여 중뇌 솔기핵의 serotonin에 면역 반응을 보인 신경 세포체들이 활성화되어 증가되었으나 imipramine과 병용해서 투여할 때는 imipramine에 의하여 serotonin에 면역 반응을 보인 신경 세포체의 활성이 억제됨을 알 수 있었다. These experiments were performed to investigate the effect of saline, tryptophan, tryptophan-imipramine and/or imipramine on serotonin immunoreactivity in raphe nucleus of midbrain of the rats (180~200 g, body weight). The animals were injected i.p. with tryptophan (15 mg/kg) and imipramine (15 mg/kg) for 20 days. The result by immunohistochemical methods were as follows; 1. Serotonin-immunoreactive neurons in the raphe of midbrain were significantly increased in tryptophan treated group compared to imipramine treated group. 2. Serotonin-immunoreactive neurons in the raphe of midbrain were decreased in imipramine treated group compared all the other group. 3. Serotonin-immunoreactive neurons in the raphe of midbrain were significantly decreased in tryptophanimipramine treated group compared to imipramine treated group. These experiments indicated that serotonin immunoreactive neurons in raphe of midbrain were increased due to the activation of tryptophan and decreased by suppresing activation of tryptophan through imipramine treatment.

모유 수유아와 조제 분유 영양아에서 수유 방법에 따른 아미노산 농도 비교 및 혈청 트립토판 농도와 수면 유도와의 관계

정다운,김은영,양은석,박상기,박영봉,문경래 朝鮮大學校 附設 醫學硏究所 2005 The Medical Journal of Chosun University Vol.30 No.2

Objective: Sleep behavior is modulated by serotonergic neurons within the brain, and the synthesis and release of serotonin by such neurons is thought to be influenced by the availability of tryptophan, the amino acid precursor of serotonin. Formula-feeding infants have depressed plasma tryptophan concentration relative to breast milk-feeding infants. Because tryptophan alters sleep waking patterns in adults, a study was designed to determine the difference of sleep latency relative to differences in plasma tryptophan and tryptophan : large neutral amino acid (LNAA) ratio between formula-feeding infants and breast milk-feeding infants. Method: 45 newborns who were born in Chosun University Hospital from December 2002 to December 2003 were selected. The newborns were divided to three group, 15 newborns were fed breast milk and 15 newborns were fed formula A, and last 15 newborns were fed formula B. At 6 weeks and 12 weeks, infants were sampled for measuring of serum amino acid level and tryptophan, tryptophan : LNAA ratio. And we taught infants' parents to measure sleep latency that means the time after a feeding to the first episode of active REM sleep that persist ≥ 1 min. Result: 1) At 6weeks, Serum α-amino-n-butyric acid, citrulline, tryptophan level was higher in formula A group than breastmilk group (P<0.05) and proline level was lower than breast milk group (P<0.05). In formula B group, serum n-amino-n-buryric acid, citrulline, cystine, hydroxylysine, hydroxyproline, isoleucine, leucine, lysine, methionine, phenylalanine, taurine, threonine, valine levels were higher than breastmilk group (P<0.05). And Serum isoleucine, methionine, proline, valine level were higher in formula B group than formula A group (P<0.05). 2) At 12 weeks, serum glutamic acid, methionine, ornithine levels were higher in formula group A than breast milk group (P<0.05). Serum β-alanine, aspartic acid, α-amino-n-butyric acid, ethanolamine, glutamic acid, threonine level were higher in formula B group than breast milk group (P<0.05). Serum β-alanine, ethanolamine levels were higher and arginine level was lower in formula B group than formula A (P<0.05). 3) At 6 weeks, serum tryptophan concentration and tryptophan: LNAA ratio were higher in formula A group (P<0.05). Sleep latency was 21 minutes in formula group A, 24 minutes in breast milk group, 25 minutes in formula B group but there was no statistically significance (P>0.05). 4) At 12 weeks, serum tryptophan concentration and tryptophan: LNAA ratio, time after feeding to the first episode of active REM sleep were no difference with each other group. Conclusion: There is significant difference of serum amino acids between breast-feeding infants and formula-feeding infants. And serum tryptophan and tryptophan: LNAA ratio differ between brest-feeding infants and formula-feeding infants. But there is no association between serum tryptophan, tryptophan: LNM ratio and sleep latency.

Exogenous Tryptophan Aggravates Experimental Lung Fibrosis Through Activation of AKT-mTORC1 Pathway

( Ki Sung Song ),( Jisu Hong ),( Ae-rin Baek ),( Susie Chin ),( An Soo Jang ),( Do Jin Kim ),( Sung Woo Park ) 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.-

Background Using the metabolomic approach, we previously reported that lung tryptophan levels were significantly increased in IPF. However, the role of tryptophan in IPF pathogenesis remains unclear. we investigated whether regulation of tryptophan modulates the severity of lung fibrosis and to find its possible mechanism. Methods We measured the expression of main extracellular matrix components in MRC-5 cells with or without tryptophan. IPF primary fibroblasts were used to perform proliferation assay and measurement of tryptophan hydroxylase (TPH-1). Exogenous tryptophan was administrated in the bleomycin (BLM) exposed mice. Results In IPF lung lysates and fibroblast, TPH-1 protein levels were significantly increased than controls. Treatment of tryptophan increased collagen, fibronectin, and a-SMA expressions in MRC5 cells. Tryptophan dramatically augments fibroblast proliferation. Treatment of tryptophan activates AKT-mTOR C1 pathway molecules in IPF fibroblast. Exogenous tryptophan promotes BLM-induced lung damage and fibrosis in mice. Conclusions These findings suggest that overproduction of tryptophan may contribute to the IPF pathogenesis and regulation of the tryptophan pathway may have therapeutic potential in preventing lung fibrosis. This study was supported by National research foundation of Korea grant 2019R1A2C1006351.

식이 단백질 수준 및 Tryptophan 투여가 Serotonin 대사에 미치는 영향

신동순,김미경 이화여자대학교 생명과학연구소 1993 생명과학연구논문집 Vol.4 No.-

This study was desigend to confirm the effect of dietary protein level and oral administration of tryptophan on brain serotonin metabolism. Two animal experiments were conducted. The objectives and results of each research were as follows: In the first experiment, it was investigated whether administration of reserpine to Sprague-Dawely rats fed 6% or 20% casein diet induced decrease in serum tryptophan and large neutral amino acid(LNAA) concentrations. tryptophan/LNAA concentration ratio, brain tryptophan, serotonin and 5-hydroxyindoleacetic acid(5-HIAA) contents. Brain serotonin content 6% casein diet group was lower than those of 20% casein diet group. Both 6% and 20% casein diet groups administered with reserpine to induce the analogous depression, showed the notable decrease in brain serotonin content when they were compared with 20% casein diet group not administered with reserpin. Serum tryptophan/LNAA ratio and brain 5-HIAA content showed a tendency similar to the change of serotonin content, but the mean difference among all groups was not significant. From these results, it could be said that when the dietary protein level was low, brain serotonin content was decreased. The second experiment was to see the change in serum tryptophan concentration and tryptophan/LNAA ratio and brain tryptophan, serotonin and 5-HIAA content when tryptophan was administered orally to the animals treated with reserpine. Serum tryptophan concentration tended to increase in both reserpine-treated 6% and 20% casein diet groups administered with tryptophan, especially in the 6% casein diet group. Serum tryptophan/LNAA concentration ratio tended to increase in reserpine-treated 6% casein diet group, while decrease in reserpine-treated 20% casein diet group. Brain tryptophan content was increased in both reserpine-treated 6% and 20% casein diet groups. However, brain serotonin content of reserpine-treated 6% casein diet group showed a tendency to decrease, while that of reserpine-treated 20% casein group increase. Consequently, the effect of tryptophan administration on increase of brain tryptophan and serotonin content in animals treated with reserpine was far more excellent in 20% casein diet groups. It was concluded that dietary protein intake and tryptophan administration increase brain serotonin level. Accordingly, it was possible to confirm that brain function, particularly in aspect of behavior related to the serotonin, was changed with manipulation of ditary composition.

The Effect of Spray-dried Porcine Plasma and Tryptophan on Feed Intake and Performance of Weaning Piglets

Hsia, Liang Chou Asian Australasian Association of Animal Productio 2005 Animal Bioscience Vol.18 No.1

There were three trials involved in this experiment. All piglets in Trial 1 were randomly distributed into the following 4 treatments. Treatment 1. Corn-soybean diet with 5% SDPP. The tryptophan level was 0.237%. Treatment 2. Corn-soybean diet with 10% meat and bone meal. The tryptophan level was 0.177%. Treatment 3. Treatment 1+0.0662% synthetic tryptophan. The total tryptophan level was 0.303. Treatment 4. Treatment 2+0.0662% synthetic tryptophan. The total tryptophan level was 0.236. Piglets in Trial 2 were distributed randomly into the following 4 treatments. Treatment 1: corn-soybean diet+10% meat and bone meal. The total tryptophan level was 0.176%. Treatment 2: corn-soybean diet+10% meat and bone meal+5% SDPP. The total tryptophan level was 0.180%. Treatment 3: Treatment 1 diet+0.004% synthetic tryptophan. The total tryptophan level was 0.180%. Treatment 4: Treatment 1 diet+0.631% synthetic tryptophan. The total tryptophan level was 0.237%. There were 4 treatments in Trial 3. Treatment 1: cornsoybean diet+10% meat and bone meal. The total tryptophan level was 0.176%. Treatment 2: Treatment 1 diet+0.061% synthetic tryptophan. The total tryptophan level was 0.237%. Treatment 3: Treatment 2 diet+0.061% synthetic tryptophan. The total tryptophan level was 0.298%. Treatment 4: corn-soybean diet+10% meat and bone meal+5% SDPP. The total tryptophan level was 0.180%. The results of Trial 1 showed that the piglets ate significantly more (p<0.05) when feed included SDPP in the diet during the first 2 weeks. The feed intake also increased when synthetic tryptophan was added in the 5% meat and bone meal diet; however, the difference did not reach a significant level (p>0.05) during the first 2 weeks. Three weeks onwards the feed intake of 5% meat and bone meal treatment was significantly lower (p<0.05) than for the other three treatments. The results of Trial 2 showed that the feed intake could be significantly improved only when the total tryptophan level reached 0.237%. Piglets in the 5% SDPP treatment had higher feed intake than piglets in 10% meat and bone meal treatment with 0.180% of tryptophan, but did not reach a significant level (p<0.05). Body weight gain also had the same trend as feed intake. The pigs in Treatment 1, the lowest total level of tryptophan treatment (0.176%), had lowest feed intake and weight gain, but the difference did not reach a significant level (p>0.05). The pigs in Treatment 1 of Trial 3 had the lowest feed intake and weight gain (p>0.05). Treatment 2 (0.237%) had the highest average feed intake from Week 1 to Week 5; the second best result was recorded in Treatment 4. As for the weight gain of the piglets in Treatment 4 (5% SDPP), they had a higher average weight during the first 3 weeks. The feed efficiency was better for Treatment 4 (5% SDPP) during the first 2 weeks. The results of these trials showed that both SDPP and tryptophan had a trend to improve the feed intake and weight gain.

Pyruvic Acid 생산 미생물과 연결된 Pyruvic Acid의 Tryptophan으로의 효소적 전환

정남현,방원기 한국미생물 · 생명공학회 1987 한국미생물·생명공학회지 Vol.15 No.5

Pyruvic acid 생산 미생물로부터 얻어진 pyruvic acid의 tryptophan으로의 효소적 전환을 조사하였다. 발광 미생물인 Beneckea sp.가 pyruvic acid의 생산에 사용되었다. pyruvic acid, indole과 ammonia로 부터 tryptophan을 합성하는 tryptophanase의 효소원으로 Enterobacter aerogenes ATCC10031의 균체가 반응용액에 직접 사용되었다. Tryptophan의 생산량을 증가시키기 위해, 비이온성 계면활성제와 비 수용성 유기용매가 indole의 저장소로 사용되었다. 비이온성 계면활성제의 경우 triton X-100은 매우 효과적이였다. 1.5%의 triton X-100 이 사용되었을 때, 37$^{\circ}C$에서 48시간 동안에 7.7g/$\ell$의 tryptophan이 생산되었다. 비수용성 유기용매의 경우 10%의 benzene이 사용되었을 때, 37$^{\circ}C$에서 48시간 동안에 8.7g/$\ell$의 tryptophan이 생산되었다. 이 tryptophan의 양은 indole과 pyruvic acid를 기준으로 각각 48%와 36%의 전환율에 해당한다. Enzymatic conversion of pyruvic acid produced by microorganism to tryptophan was investigated. A luminescent bacteria. Beneckea sp., was used for the production of pyruvic acid. As a source of tryptophanase which synthesizes tryptophan from pyruvic acid, indole and ammonia, whole cells of Enterobacter aerogenes ATCC 10031 were used directly in the reaction mixture. To increase the production of tryptophan, nonionic detergents and nonaqeous organic solvents were used ms reserviors of indole in the reaction mixture. In the case of nonionic detergents, TritonX-100 was very effective. When 1.5% of Triton X-100 was used, 7.7g/$\ell$ of tryptophan was produced at 37$^{\circ}C$ for 48hr. In the case of nonaqueous solvents, 8.7g/$\ell$ of tryptophan was produced at 37$^{\circ}C$ for 48 hr, when 10% of benzene was used. This amount of tryptophan corresponds to conversion of 48% of Indole and 36% of pyruvic acid, respectively.

The Effect of Varying Levels of Tryptophan on Growth Performance and Carcass Characteristics of Growing and Finishing Broilers

Hsia, L.C.,Hsu, J.H.,Liao, C.T. Asian Australasian Association of Animal Productio 2005 Animal Bioscience Vol.18 No.2

The purpose of this experiment was to study the effect of varying levels of tryptophan on the performance and carcass character of broiler. Trial 1: Ninety-six, five-week-old male Hubbard chickens, average weight 1.97 kg, were used in the trial. All birds were allocated into 3 treatments of 32 birds each. Each bird was kept in an individual cage. The trial period was 3 weeks. Treatment 1: Tryptophan content 0.198%. Treatment 2: Tryptophan content 0.228%. Treatment 3: Tryptophan content 0.258%. Trial 2: Ninety-six, three-week-old male Hubbard chickens, average weight 1.23 kg, were randomly distributed into the following two treatments. Each treatment had 48 birds. Treatment 1: Tryptophan content 0.167%. Treatment 2: Tryptophan content 0.198%. Trial 3: Ninety-six, twoweek-old Hubbard chickens, average body weight 0.72 kg, were used in this experiment. There were three treatments as follows. Treatment 1. Tryptophan content 0.136%. Treatment 2. Tryptophan content 0.167%. Treatment 3. Tryptophan content 0.198%. The result of Trial 1 showed that the feed intake, performance, and carcass characteristics were not influenced by tryptophan content in the diet which between 0.198% and 0.258% (p>0.05). There was no significant difference (p>0.05) in feed intake in either treatment in Trial 2. However, weight gain, feed conversion efficiency, and most carcass characteristics in the 0.198% treatment were significantly better (p<0.05) than in the 0.167% treatment. There was a trend that feed intake increased with increasing level of tryptophan, but there was no significant difference in Trial 3. The weight gain and feed conversion efficiency were significantly reduced for the broiler in the 0.136% treatment. This series of experiment showed that broilers need about 0.198% of tryptophan.

Inhibitory Effects of 5-Hydroxytryptamine and Trytophan an Metal Ions and Reactive Oxygen Species-induced Liqid Peroxidation

Ham, Dong Suk,Shin, Yong Kyoo,Lee, Chung Soo 중앙대학교 의과대학 의과학연구소 1994 中央醫大誌 Vol.19 No.2

5-Hydroxytryptamin과 5-hydroxytryptophan은 마이크로조움과 미토콘드리아의 비효소성 지질 과산화를 억제한다고 제시되고 있으나, 이들의 항산화 작용기전은 밝혀지고 있지 않다. 본 연구에서는 Fe_2+ 단독 또는 Cu^2+와 H_2O_2에 의한 간 마이크로조움의 산화성 손상에 나타내는 5-hydroxytryptamine(5-HT)과 tryptophan의 효괄르 관찰하였다. 이들의 효과를 지질 과산화와 반응성 산소대사물에 대한 제거 작용으로써 조사하였다. Fe^2+ 단독 또는 Cu^2+와 H_2O_2에 의한 마이크로조움의 지질 과산화는 5-HT에 의하여 용량에 따라 뚜렷하게 억제되었으며 tryptophan에 의하여 억제되었다. Fe^2+에 의한 지질 과산화는 SOD, DABCO와 DETAPAC에 의하여 억제되었고 catalase, DMSO와 sodium formate에 의하여 약간 억제되었다. Cu^2+와 H_2O_2의 과산화 작용은 catalase와 DABCO에 의하여 억제되었고 sodium formate에 의하여 약간 억제되었으나 DMSO는 유의한 효과를 나타내지 않았다. Ferricytochrome c는 Fe^2+첨가에 따라 환원되었으며 이러한 환원은 SOD와 tryptophan에 의하여 효과적으로 억제되었다. Fe^2+ 단독 또는 xanthine과 xanthine oxidase의 존재하에서 OHㆍ생성은 5-HT, tryptophan과 DMSO에 의하여 억제되었다. 자외선 조사에 따른 ^1O_2의 생성은 DABCO에 의하여 억제되었으나 5-HT와 tryptophan의 영향은 받지 않았다. 이상의 결과로부터 5-HT와 tryptophan은 O^-ㆍ_2와 OHㆍ 같은 반응성 산소대사물과 아마도 산소-금속이온 복합체에 대한 제거 작용으로써 H_2O_2가 있거나 없는 상태에서 금속이온에 의한 지질 과산화를 포함한 산화성 조직손상을 억제할 것으로 추정된다. 5-Hydroxytrytamine and 5-hydroxytryptophan have been shown to inhibit nonenzymically induced-lipid peroxidations of microsomes and mitochondria. However, the antioxidant action mechanism of them has not been elucidated. In this study, effects of 5-hydroxytryptamine and tryptophan on the oxidative injury of liver microsomes caused by either Fe^+ alone or Cu^2+ and H_2O_2 were investigated. Their effects were studied with respect to lipid peroxidation and scavenging effect on reactive oxygen intermediates. Lipid peroxidation of microsomes induced by either Fe^2+ alone or Cu^2+ and H_2O_2 was remarkably inhibited by 5-HT and was inhibited by tryptophan in a dose dependent fashion. Fe^2+ - induced lipid peroxidation was inhibited by SOD, DABCO, DETAPAC and was slightly inhibited by catalase, DMSO and sodium formate. The proxidative action of Cu^2+ and H_2O_2 was inhibited by catalase and DABCO and was slightly inhibited by sodium formate, whereas DMSO did not show any significant effect. Ferricytochrome c was reduced by the addition of Fe^2+ and the reduction was effectively inhibited by SOD and tryptophan. OHㆍ production in the presence of either Fe^2+ alone or xanthine and xanthine oxidase was inhibited by 5-HT, tryptophan and DMSO. Production of ^1O_2 by U.V. irradiation, which is inhibited by DABCO, was not affected 5-HT and tryptophan. These results suggest that 5-HT and tryptophan may inhibit the oxidative tissue injury including lipid peroxidation induced by metal ion with or without H_2O_2 though scavenging action on reactive oxygen species, such as O^-ㆍ_2 and OHㆍ and probably oxygen-metal ion complexes.

살코스키 시약과 Indole-3-acetic Acid의 반응 중 트립토판의 간섭

이슬 ( Seul Lee ),어나미까커날 ( Anamika Khanal ),여준구 ( Junkoo Yeo ),노그라도캐시린 ( Kathyleen Nogrado ),조아현 ( Ahyeon Cho ),송윤진 ( Yoonjin Song ),권미지 ( Miji Kwon ),이지훈 ( Ji-hoon Lee ) 한국환경농학회 2018 한국환경농학회 학술대회집 Vol.2018 No.-

Indole-3-acetic acid (IAA) is the most common auxin hormone produced in the plant and is very important because it regulates various aspects of plant growth and development. Tryptophan is the main precursor for IAA while IAA can be synthesized by two pathways i.e., tryptophan-dependent pathway and tryptophan-independent pathway. There have been many studies using Salkowski regent to measure the IAA production by bacteria. In this study, we have found that there was the interference of tryptophan on the colorimetric estimations of indole-3-acetic acid (IAA) by using Salkowski reagent (35% HClO4 and 10 mM FeCl3), which developed a pink color complex of tris-(indole-3-acetate) iron(III) with IAA. Moreover, we detected the effect of different concentration of tryptophan (100, 200, and 300 μM) on different concentration of IAA (100, 200, and 300 μM). The absorbance on IAA for the tested concentrations was found to be increased with the increasing concentration of tryptophan. It seems that both the IAA and tryptophan show the maximum absorbance at the similar wavelengths. It was also observed that the difference between the predicted and measured concentrations of IAA became larger as the predicted IAA concentration decreased. From this study, it is expected that tryptophan would interfere with accurate measurements of IAA, and therefore care should be taken for the measurement of IAA generated by the precursor, tryptophan.

Tryptophan-derived Alkaloids from Hedera rhombea Fruits and Their Butyrylcholinesterase Inhibitory Activity

Manh Tuan Ha,박세은,김정아,우미희,Jae Sue CHOI,민병선 한국생약학회 2022 Natural Product Sciences Vol.28 No.3

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease in industrialized countries. It is estimated that about 47 million people living with dementia and the number of cases will be tripled by 2050. However, the exact mechanism of AD is not known, and full therapy has still not been found. Various tryptophan-derived alkaloids have been reported as promising agents for the treatment of AD. In the present study, a series of tryptophan-derived alkaloids were isolated and characterized from the methanol extract of Hedera rhombea fruit. Based on the analysis of their observed and reported spectroscopic data, their structures were identified as N-[4′-hydroxy-(E)-cinnamoyl]-L-tryptophan (1), N-[3′,4′-dihydroxy-(E)-cinnamoyl]-L-tryptophan (2), N-[4′-hydroxy-(E)-cinnamoyl]-L-tryptophan methyl ester (3), and N-[3′,4′-dihydroxy-(E)-cinnamoyl]-L-tryptophan methyl ester (4). These compounds were screened for anti-Alzheimer activity via their inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes in vitro. As a result, compounds 3 and 4 showed moderate BChE inhibition with IC50 values of 86.9 and 78.4 µM, respectively, compared to those of the positive control [berberine (IC50 = 11.5 µM)]. However, all four compounds did not show significant inhibition of the AChE enzyme. This is the first time, the AChE and BChE inhibitory activities of these tryptophan-derived alkaloids were investigated and reported.