bims-supasi 2023-10-08 papers

Issue of 2023‒10‒08
three papers selected by
Jonathan Wolf Mueller, University of Birmingham

Pharmacol Ther. 2023 Sep 28. pii: S0163-7258(23)00204-8. [Epub ahead of print]251 108540

Sulfoconjugation of protein peptides and glycoproteins in physiology and diseases.

Pengfei Xu, Xinran Cai, Xiuchen Guan, Wen Xie.

Protein sulfoconjugation, or sulfation, represents a critical post-translational modification (PTM) process that involves the attachment of sulfate groups to various positions of substrates within the protein peptides or glycoproteins. This process plays a dynamic and complex role in many physiological and pathological processes. Here, we summarize the importance of sulfation in the fields of oncology, virology, drug-induced liver injury (DILI), inflammatory bowel disease (IBD), and atherosclerosis. In oncology, sulfation is involved in tumor initiation, progression, and migration. In virology, sulfation influences viral entry, replication, and host immune response. In DILI, sulfation is associated with the incidence of DILI, where altered sulfation affects drug metabolism and toxicity. In IBD, dysregulation of sulfation compromises mucosal barrier and immune response. In atherosclerosis, sulfation influences the development of atherosclerosis by modulating the accumulation of lipoprotein, and the inflammation, proliferation, and migration of smooth muscle cells. The current review underscores the importance of further research to unravel the underlying mechanisms and therapeutic potential of targeting sulfoconjugation in various diseases. A better understanding of sulfation could facilitate the emergence of innovative diagnostic or therapeutic strategies.

Keywords: Atherosclerosis; Drug-induced liver injury; Glycoproteins; Inflammatory bowel disease; Oncology; Protein peptides; Sulfoconjugation; Virology

DOI: https://doi.org/10.1016/j.pharmthera.2023.108540

Food Res Int. 2023 Nov;pii: S0963-9969(23)00894-3. [Epub ahead of print]173(Pt 1): 113349

The level of sulfate substitution of polysaccharide regulates thermal-induced egg white protein gel properties: The characterization of gel structure and intermolecular forces.

Ting Zhang, Yixin Yuan, Xinling Wu, Peixin Yu, Jinghong Ji, Jiale Chai, Ramesh Kumar Saini, Jingbo Liu, Xiaomin Shang.

Sulfated polysaccharides exhibit great potential for regulating protein-protein interactions. In the present study, three sulfated microcrystalline cellulose (MCS) with different degrees of sulfate substitution (DSS: 0.33, 0.51, 0.61) were synthesized and the effects of DSS on the regulation of egg white protein (EWP) aggregation and gelation properties were investigated. The results found that the improvement of protein mechanical properties by MCS is closely related to the level of sulfate substitution. The higher the DSS, the more ordered protein aggregates and compact gel network formed during heating as compared to that of pure EWP. Lower DSS (0.33) shows little effect on the mechanical properties of EWP. Furthermore, all the MCSs could significantly destroy the tertiary structure of protein molecules during heating, while for the secondary structure, MCS with higher DSS (0.51 and 0.61) could effectively control the decreasing tendency of α-helix and increasing tendency of β-sheet. Hydrophobic interactions were recognized as the major intermolecular force in the compact mixed gels (EWP/MCS2 and EWP/MCS3 gels, DSS was 0.51 and 0.61, respectively). These findings provide a vital understanding of the gelling mechanism of the protein-polysaccharide system and the application of sulfated polysaccharides in protein-based food products.

Keywords: Cellulose sulfates; Degrees of substitution; Egg white protein; Gelation

DOI: https://doi.org/10.1016/j.foodres.2023.113349

Lipids Health Dis. 2023 Oct 03. 22(1): 164

Fecal short chain fatty acids and urinary 3-indoxyl sulfate do not discriminate between patients with Crohn´s disease and ulcerative colitis and are not of diagnostic utility for predicting disease severity.

Hauke Christian Tews, Tanja Elger, Stefan Gunawan, Tanja Fererberger, Stefanie Sommersberger, Johanna Loibl, Muriel Huss, Gerhard Liebisch, Martina Müller, Arne Kandulski, Christa Buechler.

BACKGROUND: Urinary 3-indoxyl sulfate levels as well as fecal short chain fatty acid (SCFA) concentrations are surrogate markers for gut microbiota diversity. Patients with inflammatory bowel diseases (IBDs) and patients with primary sclerosing cholangitis (PSC), a disease closely associated with IBD, have decreased microbiome diversity. In this paper, the fecal SCFAs propionate, acetate, butyrate and isobutyrate of patients with IBD and patients with PSC-IBD and urinary 3-indoxyl sulfate of IBD patients were determined to study associations with disease etiology and severity.METHODS: SCFA levels in feces of 64 IBD patients and 20 PSC-IBD patients were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Urinary 3-indoxyl sulfate levels of 45 of these IBD patients were analysed by means of reversed-phase liquid chromatography-electrospray ionization-tandem mass spectrometry. Feces of 17 healthy controls and urine of 13 of these controls were analyzed in parallel. These cohorts had comparable sex distribution and age.
RESULTS: Urinary 3-indoxyl sulfate concentrations (normalized to urinary creatinine levels) was increased (P = 0.030) and fecal isobutyrate levels (normalized to dry weight of the stool sample) of IBD patients were decreased (P = 0.035) in comparison to healthy controls. None of the analyzed metabolites differed between patients with Crohn´s disease (CD) and patients with ulcerative colitis (UC). Fecal acetate and butyrate positively correlated with fecal calprotectin (P = 0.040 and P = 0.005, respectively) and serum C-reactive protein (P = 0.024 and P = 0.025, respectively) in UC but not CD patients. UC patients with fecal calprotectin levels above 150 µg/g, indicating intestinal inflammatory activity, had higher fecal acetate (P = 0.016), butyrate (P = 0.007) and propionate (P = 0.046) in comparison to patients with fecal calprotectin levels < 50 µg/g. Fecal SCFA levels of PSC-IBD and IBD patients were comparable.
CONCLUSIONS: Current findings suggest that analysis of urinary 3-indoxyl-sulfate as well as fecal SCFAs has no diagnostic value for IBD and PSC-IBD diagnosis or monitoring of disease severity.

Keywords: Acetate; Biomarker; Butyrate; Calprotectin; Crohn´s disease; IBD; Ulcerative colitis

DOI: https://doi.org/10.1186/s12944-023-01929-6