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Tryptophan-tagged peptide from serine threonine-protein kinase of Channa striatus improves antioxidant defence in L6 myotubes and attenuates caspase 3-dependent apoptotic response in zebrafish larvae

Issac PK, Lite C, Guru A, Velayutham M, Kuppusamy G, Saraswathi NT, et al.

Fish Physiol Biochem, 2021 Apr;47(2):293-311.
PMID: 33394283 DOI: 10.1007/s10695-020-00912-7

This study reports the antioxidant property and molecular mechanism of a tryptophan-tagged peptide derived from a teleost fish Channa striatus of serine threonine-protein kinase (STPK). The peptide was tagged with tryptophan to enhance the antioxidant property of STPK and named as IW13. The antioxidant activity of IW13 peptide was investigated using in vitro methods such as DPPH, ABTS, superoxide anion radical scavenging and hydrogen peroxide scavenging assay. Furthermore, to investigate the toxicity and dose response of IW13 peptide on antioxidant defence in vitro, L6 myotubes were induced with generic oxidative stress due to exposure of hydrogen peroxide (H2O2). IW13 peptide exposure was found to be non-cytotoxic to L6 cells in the tested concentration (10, 20, 30, 40 and 50 μM). Also, the pre-treatment of IW13 peptide decreased the lipid peroxidation level and increased glutathione enzyme activity. IW13 peptide treatment upregulated the antioxidant enzyme genes: GPx (glutathione peroxidase), GST (glutathione S transferase) and GCS (glutamine cysteine synthase), in vitro in L6 myotubes and in vivo in zebrafish larvae against the H2O2-induced oxidative stress. The results demonstrated that IW13 renders protection against the H2O2-induced oxidative stress through a cellular antioxidant defence mechanism by upregulating the gene expression, thus enhancing the antioxidant activity in the cellular or organismal level. The findings exhibited that the tryptophan-tagged IW13 peptide from STPK of C. striatus could be a promising candidate for the treatment of oxidative stress-associated diseases.

Matched MeSH terms: Tryptophan
Fulltext Purple urine bag syndrome: a startling phenomenon of purple urine in a urine drainage bag. A primary care approach and literature review

Wong, Y.W.E., Abdullah, N.

Malaysian Family Physician, 2018;13(2):42-44.
MyJurnal

Purple urine bag syndrome (PUBs) is a rare and startling phenomenon of purple discolouration
in the urine or urinary catheter and bag. It is reported in chronically debilitated elderly patients,
mostly in women on long-term urinary catheters. Its prevalence is strikingly more common in
nursing home residents. Several factors contribute to the formation of indigo (blue) and indirubin
(red) pigments from a breakdown of dietary tryptophan, which stains the urine purple. These
factors include constipation, dysmotility of the bowel, bowel bacterial overgrowth, dehydration, and
urinary tract infection. The presence of purple urine may cause undue alarm to both the patient and
the doctor. Thus, we present this case report on an 86-year-old woman, a nursing home resident
on a long-term urinary catheter, who presented to the primary care clinic. Her urine cleared
after antibiotic therapy, replacement of her urinary catheter, and supportive management, which
included hydration and nutrition. In addition to these measures, reducing the time between urinary
catheter changes was recommended to prevent recurrence of this condition.

Matched MeSH terms: Tryptophan
Alteration of plasma alanine, glutamate, and glycine Level: A potentiate manic episode of bipolar disorder

Wan Nasru WN, Ab Razak A, Yaacob NM, Wan Azman WN

Malays J Pathol, 2021 Apr;43(1):25-32.
PMID: 33903302

INTRODUCTION: The amino acids that function as co-agonists at the N-methyl-D-aspartate (NMDA) receptor have been investigated in bipolar disorder (BD). However, studies comparing amino acid levels in the plasma of BD patients with healthy controls have yielded inconsistent results. We, therefore, conducted a study in Hospital Universiti Sains Malaysia to determine the plasma levels of glutamate, glycine, and alanine in BD patients and compared them with the healthy controls.
MATERIALS AND METHODS: An overnight fast of 10-hour plasma levels of glutamate, glycine, alanine, and tryptophan were measured in 83 bipolar patients, and were compared to a group of 82 healthy controls.
RESULTS: The mean (SD) age of bipolar patients was 40.9 (12.1), while the mean (SD) age for control groups was 35.6 (7.7) years. The median (25th, 75th percentile) of glutamate and alanine levels in bipolar patients was 111.0 (65.0,176.0) and 530.0 (446.0,629.0), respectively, while the mean (SD) of glycine level in bipolar patients was 304.0 (98.1). Significant higher glutamate, glycine, and alanine levels were found in bipolar disorder patients in the manic episode as compared to the healthy controls.
CONCLUSION: Although the exact relationship between peripheral NMDA receptor co-agonist levels in the pathogenesis of BD is not well understood, these findings should be explored and may enlighten some new paths for BD therapy which could reward the patients also clinicians.

Matched MeSH terms: Tryptophan
Fulltext Investigation Trp64Arg polymorphism of the beta 3-adrenergic receptor gene in nonobese women with polycystic ovarian syndrome

Zangeneh FZ, Shoushtari MS, Shojaee S, Aboutorabi E

Int J Reprod Biomed, 2020 Mar;18(3):165-174.
PMID: 32309765 DOI: 10.18502/ijrm.v18i3.6712

Background: Polycystic ovary syndrome (PCOS) is a multifactorial and heterogeneous disease that has a potent inheritable component based on familial clustering. Despite many studies in the genetic field of PCOS, the genes that are involved in the causes of this syndrome have not been thoroughly investigated.
Objective: The purpose of this study was to establish the occurrence of the Trp64Arg polymorphism of beta3 adrenergic receptor in non-obese women with PCOS.
Materials and Methods: This cross-sectional study was performed on 100 women with PCOS and normal women as the control group in Imam Khomeini Hospital of Tehran in 2016-2017. Peripheral blood sample (2 cc) was obtained from two groups for genomic DNA based on the gene bank. Polymorphisms were genotyped by of using ADRB3 Trp64Arg. Then the DNA was extracted by genomic kiagen kit. The primer was analyzed for PCR based on gene bank by using Primer3 software and then confirmed by primer Blast tool at NCBI site to conformity to the beta-3 adrenergic receptor gene. The protein changes were assessment by the Clastal W software.
Results: The sequence analysis presented in NCBI, transcript variant 1, with the code NM_000025.2, shows changes in the amino acid sequence of exon 1 in women with PCOS. Polymorphism in the codon 64 encoding the amino acid tryptophan (W) occurred in the nucleotide c.T190C, which changed the nucleotide T to C and then the amino acid sequence of the tryptophan was altered to arginine pW64R.
Conclusion: T-C polymorphism is evident in the codon 64 of the adrenergic β3 receptor in patients with PCOS. Therefore, Beta3 adrenergic receptor gene polymorphism (Thr164Ile) associates with this syndrome in nonobese women.

Matched MeSH terms: Tryptophan
Studies of the chemical composition of a healing skin wound in rats, and of the concentrations of some constituents of tissues distant from the healing wound

Candlish J, Chandra N

Biochem. J., 1967 Mar;102(3):767-73.
PMID: 16742493

1. A skin lesion was made in rats by dorsal incision and the insertion of a polythene tube. 2. Over a period of 25 days after wounding, assays were performed for ascorbic acid, DNA, hydroxyproline, methionine, tryptophan, tyrosine and free amino acids in the lesion tissue. 3. The neutral-salt-soluble proteins of the lesion tissue were fractionated on DEAE-Sephadex, with the separation of fibrinogen and gamma-globulin from a serum protein fraction. 4. Over a period of 20 days after wounding, in wounded rats and in controls, assays were conducted for: ascorbic acid in lens and liver, hydroxyproline, soluble protein, methionine and water in muscle and tendon, and free amino acids in muscle. 5. Relative to controls there was a decrease in lens and liver ascorbic acid, a rise in tendon hydroxyproline, a rise in muscle free amino acids, a fall in muscle protein and a rise in tendon and muscle water.

Matched MeSH terms: Tryptophan
Fulltext Purple urine bag syndrome: A startling phenomenon of purple urine in a urine drainage bag. A primary care approach and literature review

Wong Y, Abdullah N

Malays Fam Physician, 2018;13(2):42-44.
PMID: 30302185

Purple urine bag syndrome (PUBs) is a rare and startling phenomenon of purple discolouration in the urine or urinary catheter and bag. It is reported in chronically debilitated elderly patients, mostly in women on long-term urinary catheters. Its prevalence is strikingly more common in nursing home residents. Several factors contribute to the formation of indigo (blue) and indirubin (red) pigments from a breakdown of dietary tryptophan, which stains the urine purple. These factors include constipation, dysmotility of the bowel, bowel bacterial overgrowth, dehydration, and urinary tract infection. The presence of purple urine may cause undue alarm to both the patient and the doctor. Thus, we present this case report on an 86-year-old woman, a nursing home resident on a long-term urinary catheter, who presented to the primary care clinic. Her urine cleared after antibiotic therapy, replacement of her urinary catheter, and supportive management, which included hydration and nutrition. In addition to these measures, reducing the time between urinary catheter changes was recommended to prevent recurrence of this condition.

Matched MeSH terms: Tryptophan
Exendin-4 from Heloderma suspectum venom: From discovery to its latest application as type II diabetes combatant

Yap MKK, Misuan N

Basic Clin Pharmacol Toxicol, 2018 Nov 12.
PMID: 30417596 DOI: 10.1111/bcpt.13169

Type II diabetes mellitus (T2DM) is a chronic non-communicable disease due to abnormal insulin actions causing uncontrolled hyperglycaemia. The treatment for T2DM, for instance, metformin and incretin mimetic, mainly focuses on the restoration of insulin sensitivity and secretion. Exendin-4 is a short incretin-mimetic peptide consisting of 39 amino acids. It is discovered in the venom of Heloderma suspectum as a full agonist for the glucagon-like peptide 1 (GLP-1) receptor and produces insulinotropic effects. It is more resistant to enzymatic degradation by dipeptidyl-peptidase-4 and has a longer half-life than the endogenous GLP-1; thus, it is further developed as an incretin hormone analogue used to treat T2DM. The helical region of the peptide first interacts with the extracellular N-terminal domain (NTD) of GLP-1 receptor while the C-terminal extension containing the tryptophan cage further enhances its binding affinity. After binding to the NTD of the receptor, it may cause the receptor to switch from its auto-inhibited state of the receptor to its auto-activated state. Exendin-4 enhances the physiological functions of β-cells and the up-regulation of GLP-1 receptors, thus reducing the plasma glucose levels. Moreover, exendin-4 has also been found to ameliorate neuropathy, nephropathy and ventricular remodelling. The therapeutic effects of exendin-4 have also been extrapolated into several clinical trials. Although exendin-4 has a reasonable subcutaneous bioavailability, its half-life is rather short. Therefore, several modifications have been undertaken to improve its pharmacokinetics and insulinotropic potency. This review focuses on the pharmacology of exendin-4 and the structure-function relationships of exendin-4 with GLP-1 receptor. The review also highlights some challenges and future directions in the improvement of exendin-4 as an anti-diabetic drug.

Matched MeSH terms: Tryptophan
Fulltext A fascinating case of the ‘purple urine bag syndrome'

Low, Qin Jian, Lim, Tzyy Hue, Teoh, Kuo Zhau, Siow, Garry Peir Woeei, Go, Zher Lin, Tee, Vern Jun, et al.

Borneo Journal of Medical Sciences, 2018;12(3):59-62.
MyJurnal

Purple urine bag syndrome (PUBS) is a rare presentation of urinary tract infections (UTIs). It is commonly seen in constipated patients. There is a deep purple discoloration of contents of urine bag due to presence of indigo and indirubin pigments which are metabolites of tryptophan. We would like to describe an interesting case of purple urine bag syndrome of 88-year-old woman who presented with catheter-related urinary tract infection. She had low-grade fever and suprapubic discomfort for three days duration. She had increased white cell count and C-reactive peptide (CRP). Urinalysis showed protein 2+, nitrite and leucocyte esterase positive. Urine culture grew Escherichia coli and Klebsiella pneumoniae. She was treated with oral cefuroxime and recovered. This case report may be the first case of PUBS reported in this region.

Matched MeSH terms: Tryptophan
Fulltext Global serum metabolomics profiling of colorectal cancer

Hashim NAA, Ab-Rahim S, Suddin LS, Saman MSA, Mazlan M

Mol Clin Oncol, 2019 Jul;11(1):3-14.
PMID: 31289671 DOI: 10.3892/mco.2019.1853

Accurate diagnosis of colorectal cancer (CRC) relies on the use of invasive tools such as colonoscopy and sigmoidoscopy. Non-invasive tools are less sensitive in detecting the disease, particularly in the early stage. A number of researchers have used metabolomics analyses on serum/plasma samples of patients with CRC compared with normal healthy individuals in an effort to identify biomarkers for CRC. The aim of the present review is to compare reported serum metabolomics profiles of CRC and to identify common metabolites affected among these studies. A literature search was performed to include any experimental studies on global metabolomics profile of CRC using serum/plasma samples published up to March 2018. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used to assess the quality of the studies reviewed. In total, nine studies were included. The studies used various analytical platforms and were performed on different populations. A pathway enrichment analysis was performed using the data from all the studies under review. The most affected pathways identified were protein biosynthesis, urea cycle, ammonia recycling, alanine metabolism, glutathione metabolism and citric acid cycle. The metabolomics analysis revealed levels of metabolites of glycolysis, tricarboxylic acid cycle, anaerobic respiration, protein, lipid and glutathione metabolism were significantly different between cancer and control samples. Although the majority of differentiating metabolites identified were different in the different studies, there were several metabolites that were common. These metabolites include pyruvic acid, glucose, lactic acid, malic acid, fumaric acid, 3-hydroxybutyric acid, tryptophan, phenylalanine, tyrosine, creatinine and ornithine. The consistent dysregulation of these metabolites among the different studies suggest the possibility of common diagnostic biomarkers for CRC.

Matched MeSH terms: Tryptophan
Fulltext Denaturing gradient-gel electrophoresis screening of familial defective apolipoprotein B-100 in a mixed Asian cohort: two cases of arginine3500-->tryptophan mutation associated with a unique haplotype

Choong ML, Koay ES, Khoo KL, Khaw MC, Sethi SK

Clin Chem, 1997 Jun;43(6 Pt 1):916-23.
PMID: 9191540

The Arg-to-Trp substitution at codon 3500 in the apolipoprotein (apo) B-100 gene is established as a cause of familial defective apo B-100 (FDB), a functional mutation, resulting in reduced LDL receptor binding and manifest hypercholesterolemia. In a search for similar mutations in 163 Malaysians, we screened the putative receptor-binding region (codons 3456-3553) of the apo B-100 gene by PCR amplification and denaturing gradient-gel electrophoresis. Four single-base mutations were detected and confirmed by DNA sequencing. Two females, a Chinese and a Malay, had the same CGG3500-->TGG mutation, resulting in an Arg3500-to-Trp substitution. This is the second published report of such an independent mutation involving the same codon as the established Arg3500-to-Gln mutation. The two other mutations detected, CTT3517-->CTG and GCC3527-->GCT, resulted in degenerate codons with no amino acid substitutions. All four mutations were associated with a unique apo B haplotype, different from those found in Caucasian FDB patients but concurring with that previously reported for two other Asians with FDB.

Matched MeSH terms: Tryptophan/genetics*
Fulltext HIV/Human herpesvirus co-infections: Impact on tryptophan-kynurenine pathway and immune reconstitution

Yap SH, Abdullah NK, McStea M, Takayama K, Chong ML, Crisci E, et al.

PLoS One, 2017;12(10):e0186000.
PMID: 29016635 DOI: 10.1371/journal.pone.0186000

BACKGROUND: Co-infections with human herpesvirus (HHV) have been associated with residual chronic inflammation in antiretroviral (ART)-treated human immunodeficiency virus (HIV)-infected individuals. However, the role of HHV in modulating the tryptophan-kynurenine pathway and clinical outcomes in HIV-infected individuals is poorly understood. Thus, we investigated the seroprevalence of four common HHVs among treated HIV-infected participants and their impact on kynurenine/tryptophan (K/T) ratio and long-term CD4 T-cell recovery in HIV/HHV co-infected participants.
METHOD: In this cross-sectional study, HIV-infected participants receiving suppressive ART for a minimum of 12 months were recruited from the University Malaya Medical Centre (UMMC), Malaysia. Stored plasma was analyzed for CMV, VZV, HSV-1 and HSV-2 IgG antibody levels, immune activation markers (interleukin-6, interferon-γ, neopterin and sCD14), kynurenine and tryptophan concentrations. The influence of the number of HHV co-infection and K/T ratio on CD4 T-cell recovery was assessed using multivariate Poisson regression.
RESULTS: A total of 232 HIV-infected participants were recruited and all participants were seropositive for at least one HHV; 96.1% with CMV, 86.6% with VZV, 70.7% with HSV-1 and 53.9% with HSV-2. K/T ratio had a significant positive correlation with CMV (rho = 0.205, p = 0.002), VZV (rho = 0.173, p = 0.009) and a tendency with HSV-2 (rho = 0.120, p = 0.070), with CMV antibody titer demonstrating the strongest modulating effect on K/T ratio among the four HHVs assessed in SOM analysis. In multivariate analysis, higher K/T ratio (p = 0.03) and increasing number of HHV co-infections (p<0.001) were independently associated with poorer CD4 T-cell recovery following 12 months of ART initiation.
CONCLUSION: Multiple HHV co-infections are common among ART-treated HIV-infected participants in the developing country setting and associated with persistent immune activation and poorer CD4 T-cell recovery.

Matched MeSH terms: Tryptophan/metabolism
Early-life citalopram-induced impairments in sexual behavior and the role of androgen receptor

Soga T, Wong DW, Putteeraj M, Song KP, Parhar IS

Neuroscience, 2012 Dec 6;225:172-84.
PMID: 22960312 DOI: 10.1016/j.neuroscience.2012.08.061

Postnatal treatment with selective serotonin reuptake inhibitors (SSRIs) has been found to affect brain development and the regulation of reproduction in rodent models. The normal masculinization process in the brain requires a transient decrease in serotonin (5-HT) levels in the brain during the second postnatal week. Strict regulation of androgen receptor (AR) and gonadotropin-releasing hormone (GnRH) expression is important to control male reproductive activity. Therefore, this study was designed to examine the effects of a potent SSRI (citalopram) on male sexual behavior and expression levels of AR and GnRH in adult male mice receiving either vehicle or citalopram (10mg/kg) daily during postnatal days 8-21. The citalopram-treated male mice showed altered sexual behavior, specifically a significant reduction in the number of intromissions preceding ejaculation compared with the vehicle-treated mice. The citalopram-treated male mice displayed elevated anxiety-like behavior in an open field test and lower locomotor activity in their home cage during the subjective night. Although there was no change in GnRH and AR mRNA levels in the preoptic area (POA), quantified by real-time polymerase chain reaction, immunostained AR cell numbers in the medial POA were decreased in the citalopram-treated male mice. These results suggest that the early-life inhibition of 5-HT transporters alters the regulation of AR expression in the medial POA, likely causing decreased sexual behavior and altered home cage activity in the subjective night.

Matched MeSH terms: Tryptophan Hydroxylase/genetics; Tryptophan Hydroxylase/metabolism

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