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H2S, Polysulfides, and Enzymes: Physiological and Pathological Aspects...
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H2S, Polysulfides, and Enzymes: Physiological and Pathological Aspects: 2nd Edition

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (31 July 2024) | Viewed by 7076

Special Issue Editors

Dr. Maria Wróbel

E-Mail Website
Guest Editor
Chair of Medical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, 31034 Kraków, Poland
Interests: biochemistry; medical biochemistry; tissue-specific expression and function of sulfurtransferases
Special Issues, Collections and Topics in MDPI journals
Dr. Halina Jurkowska

E-Mail Website
Guest Editor
Chair of Medical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, 31034 Kraków, Poland
Interests: biochemistry; anticancer research; amino acids; pharmacological reports

Special Issue Information

Dear Colleagues,

This Special Issue was organized with the intent of elucidating novel physiological and pathological functions of H2S and polysulfides and explaining the regulation of the pathways and enzymes involved in their biosynthesis. We expect this Issue to advance scientific knowledge regarding the exact functions of H2S and polysulfides and the general properties and regulation of the enzymes involved in their metabolism, including cystathionine β-synthase (EC 4.2.1.22, CBS), cystathionine γ-lyase (EC 4.4.1.1, CTH), thiosulfate sulfurtransferase (EC 2.8.1.1, rhodanese, TST), and 3-mercaptopyruvate sulfurtransferase (EC 2.8.1.2, MST). Five topics will be covered: the biosynthesis of H2S and polysulfides; biosynthetic enzymes, as well as their properties and regulation; H2S-releasing pharmaceuticals; the physiological role of H2S and polysulfides in, e.g., synaptic transmission, vascular tone, inflammation, angiogenesis; and their role in several pathological processes, e.g., healing of ulcers, neurological disorders, myocardial infarction, ischemia–reperfusion injury, heart failure, carcinogenesis, pulmonary, renal, and hepatic diseases, and diabetes. We encourage scientists studying H2S and polysulfides (mechanisms of biosynthesis, functions, and clinical usage) and related enzymes (structure, reaction mechanisms, and regulation of enzymatic activity) to contribute to this Special Issue. Research articles, clinical studies, and reviews are welcome. For authors interested in submitting a paper, please refer to the Biomolecules “Author Guidelines”.

Dr. Maria Wróbel
Dr. Halina Jurkowska
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • H2S and polysulfide
  • H2S in inflammation
  • H2S in brain, heart, liver, kidney, and pulmonary diseases
  • H2S in cancer cells
  • H2S in the pathogenesis of diabetes
  • H2S and polysulfides biosynthetic enzymes
  • H2S precursors

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Published Papers (4 papers)

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Research

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17 pages, 4608 KiB  
Article
Slow H2S-Releasing Donors and 3D Printable Arrays Cellular Models in Osteo-Differentiation of Mesenchymal Stem Cells for Personalized Therapies
by Ilaria Arciero, Silvia Buonvino and Sonia Melino
Biomolecules 2024, 14(11), 1380; https://doi.org/10.3390/biom14111380 - 30 Oct 2024
Viewed by 567
Abstract
The effects of the hydrogen sulfide (H2S) slow-releasing donor, named GSGa, a glutathione-conjugate water-soluble garlic extract, on human mesenchymal stem cells (hMSCs) in both bidimensional (2D) and three-dimensional (3D) cultures were investigated, demonstrating increased expression of the antioxidant enzyme HO-1 and [...] Read more.
The effects of the hydrogen sulfide (H2S) slow-releasing donor, named GSGa, a glutathione-conjugate water-soluble garlic extract, on human mesenchymal stem cells (hMSCs) in both bidimensional (2D) and three-dimensional (3D) cultures were investigated, demonstrating increased expression of the antioxidant enzyme HO-1 and decreased expression of the pro-inflammatory cytokine interleukin-6 (IL-6). The administration of the H2S donor can therefore increase the expression of antioxidant enzymes, which may have potential therapeutic applications in osteoarthritis (OA). Moreover, GSGa was able to promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), but not of cardiac mesenchymal stem cells (cMSCs) in a 2D culture system. This result highlights the varying sensitivity of hMSCs to the H2S donor GSGa, suggesting that the induction of osteogenic differentiation in stem cells by chemical factors is dependent on the tissue of origin. Additionally, a 3D-printable mesenchymal stem cells–bone matrix array (MSCBM), designed to closely mimic the stiffness of bone tissue, was developed to serve as a versatile tool for evaluating the effects of drugs and stem cells on bone repair in chronic diseases, such as OA. We demonstrated that the osteogenic differentiation process in cMSCs can be induced just by simulating bone stiffness in a 3D system. The expression of osteocalcin, RUNX2, and antioxidant enzymes was also assessed after treating MSCs with GSGa and/or increasing the stiffness of the culture environment. The printability of the array may enable better customization of the cavities, enabling an accurate replication of real bone defects. This could optimize the BM array to mimic bone defects not only in terms of stiffness, but also in terms of shape. This culture system may enable a rapid screening of antioxidant and anti-inflammatory compounds, facilitating a more personalized approach to regenerative therapy. Full article
(This article belongs to the Special Issue H2S, Polysulfides, and Enzymes: Physiological and Pathological Aspects: 2nd Edition)
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16 pages, 4551 KiB  
Article
Hypoxia-Induced Changes in L-Cysteine Metabolism and Antioxidative Processes in Melanoma Cells
by Leszek Rydz, Maria Wróbel, Klaudia Janik and Halina Jurkowska
Biomolecules 2023, 13(10), 1491; https://doi.org/10.3390/biom13101491 - 7 Oct 2023
Viewed by 1586
Abstract
This study was performed on human primary (WM115) and metastatic (WM266-4) melanoma cell lines developed from the same individual. The expression of proteins involved in L-cysteine metabolism (sulfurtransferases, and cystathionine β-synthase) and antioxidative processes (thioredoxin, thioredoxin reductase-1, glutathione peroxidase, superoxide dismutase 1) as [...] Read more.
This study was performed on human primary (WM115) and metastatic (WM266-4) melanoma cell lines developed from the same individual. The expression of proteins involved in L-cysteine metabolism (sulfurtransferases, and cystathionine β-synthase) and antioxidative processes (thioredoxin, thioredoxin reductase-1, glutathione peroxidase, superoxide dismutase 1) as well as the level of sufane sulfur, and cell proliferation under hypoxic conditions were investigated. Hypoxia in WM115 and WM266-4 cells was confirmed by induced expression of carbonic anhydrase IX and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 by the RT-PCR and Western blot methods. It was shown that, under hypoxic conditions the inhibition of WM115 and WM266-4 melanoma cell proliferation was associated with decreased expression of thioredoxin reductase-1 and cystathionine β-synthase. These two enzymes may be important therapeutic targets in the treatment of melanoma. Interestingly, it was also found that in normoxia the expression and activity of 3-mercaptopyruvate sulfurtransferase in metastatic WM266-4 melanoma cells was significantly higher than in primary melanoma WM115 cells. Full article
(This article belongs to the Special Issue H2S, Polysulfides, and Enzymes: Physiological and Pathological Aspects: 2nd Edition)
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Review

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27 pages, 2022 KiB  
Review
Hydrogen Sulfide: A Versatile Molecule and Therapeutic Target in Health and Diseases
by Aqsa Shahid and Madhav Bhatia
Biomolecules 2024, 14(9), 1145; https://doi.org/10.3390/biom14091145 - 10 Sep 2024
Viewed by 1301
Abstract
In recent years, research has unveiled the significant role of hydrogen sulfide (H2S) in many physiological and pathological processes. The role of endogenous H2S, H2S donors, and inhibitors has been the subject of studies that have aimed [...] Read more.
In recent years, research has unveiled the significant role of hydrogen sulfide (H2S) in many physiological and pathological processes. The role of endogenous H2S, H2S donors, and inhibitors has been the subject of studies that have aimed to investigate this intriguing molecule. The mechanisms by which H2S contributes to different diseases, including inflammatory conditions, cardiovascular disease, viral infections, and neurological disorders, are complex. Despite noteworthy progress, several questions remain unanswered. H2S donors and inhibitors have shown significant therapeutic potential for various diseases. This review summarizes our current understanding of H2S-based therapeutics in inflammatory conditions, cardiovascular diseases, viral infections, and neurological disorders. Full article
(This article belongs to the Special Issue H2S, Polysulfides, and Enzymes: Physiological and Pathological Aspects: 2nd Edition)
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20 pages, 2160 KiB  
Review
Hydrogen Sulfide (H2S)/Polysulfides (H2Sn) Signalling and TRPA1 Channels Modification on Sulfur Metabolism
by Hideo Kimura
Biomolecules 2024, 14(1), 129; https://doi.org/10.3390/biom14010129 - 19 Jan 2024
Cited by 6 | Viewed by 2259
Abstract
Hydrogen sulfide (H2S) and polysulfides (H2Sn, n ≥ 2) produced by enzymes play a role as signalling molecules regulating neurotransmission, vascular tone, cytoprotection, inflammation, oxygen sensing, and energy formation. H2Sn, which have additional [...] Read more.
Hydrogen sulfide (H2S) and polysulfides (H2Sn, n ≥ 2) produced by enzymes play a role as signalling molecules regulating neurotransmission, vascular tone, cytoprotection, inflammation, oxygen sensing, and energy formation. H2Sn, which have additional sulfur atoms to H2S, and other S-sulfurated molecules such as cysteine persulfide and S-sulfurated cysteine residues of proteins, are produced by enzymes including 3-mercaptopyruvate sulfurtransferase (3MST). H2Sn are also generated by the chemical interaction of H2S with NO, or to a lesser extent with H2O2. S-sulfuration (S-sulfhydration) has been proposed as a mode of action of H2S and H2Sn to regulate the activity of target molecules. Recently, we found that H2S/H2S2 regulate the release of neurotransmitters, such as GABA, glutamate, and D-serine, a co-agonist of N-methyl-D-aspartate (NMDA) receptors. H2S facilitates the induction of hippocampal long-term potentiation, a synaptic model of memory formation, by enhancing the activity of NMDA receptors, while H2S2 achieves this by activating transient receptor potential ankyrin 1 (TRPA1) channels in astrocytes, potentially leading to the activation of nearby neurons. The recent findings show the other aspects of TRPA1 channels—that is, the regulation of the levels of sulfur-containing molecules and their metabolizing enzymes. Disturbance of the signalling by H2S/H2Sn has been demonstrated to be involved in various diseases, including cognitive and psychiatric diseases. The physiological and pathophysiological roles of these molecules will be discussed. Full article
(This article belongs to the Special Issue H2S, Polysulfides, and Enzymes: Physiological and Pathological Aspects: 2nd Edition)
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