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Homocysteine in Protein Structure and Function and Human Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (30 May 2024) | Viewed by 1385

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Guest Editor
Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
Interests: Alzheimer's; autophagy; cardiovascular disease epigenetic regulation; error-editing mechanisms; evolution of peptide bond synthesis; gene expression; homocysteine; mTOR signalling neurological disease; protein modification; protein synthesis tRNA synthetase
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Special Issue Information

Dear Colleagues,

Homocysteine (Hcy) links two key metabolic pathways: the one-carbon/folate cycle, which provides one-carbon units for nucleotide and amino acid biosynthesis, and sulfur–amino acid metabolism, which regenerates methionine (Met) and provides cysteine (Cys). While Met and Cys are genetically encoded proteinogenic amino acids, Hcy is non-proteinogenic; however, although Hcy is not genetically encoded, proteins in our body have Hcy residues linked to lysine (Lys) residues via iso-peptide bonds (formed in a chemical reaction with Hcy-thiolactone, i.e., N-homocysteinylation) or to cysteine residues via disulfide bonds (S-homocysteinylation).

Proteins also contain Hcy bound by a peptide bond within the polypeptide chain. Such homocysteinylated proteins are formed either post-translationally via a copper/iron-dependent demethylation of Met residues or via a nitric-oxide-dependent translational mechanism on ribosomes, in which S-NO-Hcy substitutes for Met. Accumulating evidence suggests that N-Hcy-protein can promote cancer, diabetes, cardiovascular disease/stroke, neurodegenerative diseases, infertility, and pregnancy complications.

This Special Issue of the IJMS, entitled “Homocysteine in Protein Structure and Function and Human Disease”, will include a selection of original research papers and reviews on the molecular/cellular biology and pathophysiology of Hcy metabolites. Papers describing recent studies on N-Hcy-protein chemical biology and on the dysregulation of fundamental biological processes, such as mTOR signaling, autophagy, amyloid precursor protein processing, and others, due to N-Hcy-protein/Hcy-thiolactone/Hcy are welcomed.

Prof. Dr. Hieronim Jakubowski
Guest Editor

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Keywords

  • Alzheimer's disease
  • amyloid beta
  • autophagy
  • cardiovascular disease
  • epigenetic regulation
  • homocysteine thiolactone
  • methionyl-tRNA synthetase
  • mTOR signalling
  • protein homocysteinylation

Published Papers (1 paper)

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Research

17 pages, 7270 KiB  
Article
Effects of Aerobic Treadmill Training on Oxidative Stress Parameters, Metabolic Enzymes, and Histomorphometric Changes in Colon of Rats with Experimentally Induced Hyperhomocysteinemia
by Marija Stojanović, Dušan Todorović, Kristina Gopčević, Ana Medić, Milica Labudović Borović, Sanja Despotović and Dragan Djuric
Int. J. Mol. Sci. 2024, 25(4), 1946; https://doi.org/10.3390/ijms25041946 - 6 Feb 2024
Viewed by 849
Abstract
The aim of this study was to investigate the effects of aerobic treadmill training regimen of four weeks duration on oxidative stress parameters, metabolic enzymes, and histomorphometric changes in the colon of hyperhomocysteinemic rats. Male Wistar albino rats were divided into four groups [...] Read more.
The aim of this study was to investigate the effects of aerobic treadmill training regimen of four weeks duration on oxidative stress parameters, metabolic enzymes, and histomorphometric changes in the colon of hyperhomocysteinemic rats. Male Wistar albino rats were divided into four groups (n = 10, per group): C, 0.9% NaCl 0.2 mL/day subcutaneous injection (s.c.) 2x/day; H, homocysteine 0.45 µmol/g b.w./day s.c. 2x/day; CPA, saline (0.9% NaCl 0.2 mL/day s.c. 2x/day) and an aerobic treadmill training program; and HPA, homocysteine (0.45 µmol/g b.w./day s.c. 2x/day) and an aerobic treadmill training program. The HPA group had an increased level of malondialdehyde (5.568 ± 0.872 μmol/mg protein, p = 0.0128 vs. CPA (3.080 ± 0.887 μmol/mg protein)), catalase activity (3.195 ± 0.533 U/mg protein, p < 0.0001 vs. C (1.467 ± 0.501 U/mg protein), p = 0.0012 vs. H (1.955 ± 0.293 U/mg protein), and p = 0.0003 vs. CPA (1.789 ± 0.256 U/mg protein)), and total superoxide dismutase activity (9.857 ± 1.566 U/mg protein, p < 0.0001 vs. C (6.738 ± 0.339 U/mg protein), p < 0.0001 vs. H (6.015 ± 0.424 U/mg protein), and p < 0.0001 vs. CPA (5.172 ± 0.284 U/mg protein)) were detected in the rat colon. In the HPA group, higher activities of lactate dehydrogenase (2.675 ± 1.364 mU/mg protein) were detected in comparison to the CPA group (1.198 ± 0.217 mU/mg protein, p = 0.0234) and higher activities of malate dehydrogenase (9.962 (5.752–10.220) mU/mg protein) were detected in comparison to the CPA group (4.727 (4.562–5.299) mU/mg protein, p = 0.0385). Subchronic treadmill training in the rats with hyperhomocysteinemia triggers the colon tissue antioxidant response (by increasing the activities of superoxide dismutase and catalase) and elicits an increase in metabolic enzyme activities (lactate dehydrogenase and malate dehydrogenase). This study offers a comprehensive assessment of the effects of aerobic exercise on colonic tissues in a rat model of hyperhomocysteinemia, evaluating a range of biological indicators including antioxidant enzyme activity, metabolic enzyme activity, and morphometric parameters, which suggested that exercise may confer protective effects at both the physiological and morphological levels. Full article
(This article belongs to the Special Issue Homocysteine in Protein Structure and Function and Human Disease)
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