Protein nitration in the artery wall: a contributor to cardiovascular disease?

Redox Biochemistry and Chemistry, Journal Year: 2024, Volume and Issue: 8, P. 100032 - 100032

Published: June 1, 2024

Nitration is a well-established post-translational modification of selected free amino acids, as well proteins, lipids and nucleic acids. Considerable evidence now available for the formation long-lived species containing an added –NO2 function on aromatic rings tyrosine (Tyr) tryptophan (Trp) residues (both proteins), to purine nucleobases (and particularly guanine), unsaturated within biological systems. Multiple potential mechanisms that give rise these nitrated have been identified including reactions potent oxidant nitrating peroxynitrous acid/peroxynitrite (ONOOH/ONOO−) via oxidative heme proteins/enzymes (e.g. peroxidases) with biologically-relevant anion nitrite (NO2−). •NO2 likely be key intermediate, though involvement HNO2, NO2+ NO2Cl has also proposed. The resulting products widely employed qualitative or quantitative biomarkers nitration events in vitro vivo. Increasing suggests at least some are not benign species, pro-inflammatory actions. In this article role nitration, proteins artery wall, cardiovascular disease discussed, together emerging data suggesting low levels occur systems absence oxidants. Both stimulated endogenous may play modulating cell signaling, alter structure both cellular- extracellular contribute various inflammatory pathologies, atherosclerosis.

Language: Английский

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Small molecule probes for peroxynitrite detection

Redox Biochemistry and Chemistry, Journal Year: 2024, Volume and Issue: 10, P. 100034 - 100034

Published: July 26, 2024

Peroxynitrite (ONOO‒/ONOOH) is a short-lived but highly reactive species that formed in the diffusion-controlled reaction between nitric oxide and superoxide radical anion. It can oxidize certain biomolecules has been considered as key cellular oxidant under various pathophysiological conditions. crucial to selectively detect quantify ONOO– determine its role biological processes. In this review, we discuss approaches used ONOO‒ cell-free systems with major emphasis on small-molecule chemical probes. We review principles mechanisms responsible for formation of detectable products, plausible limitations recommend use boronate-based probes ONOO‒, they react directly rapidly ONOO–, produce minor ONOO‒‒specific kinetics mechanism have rigorously characterized. Specific experimental protocols detection cell-free, cellular, vivo using molecular are provided (as shown BOX 1, 2, 3, 4, 5, 6).

Language: Английский

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Fibrinogen post‐translational modifications are biochemical determinants of fibrin clot properties and interactions

FEBS Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 23, 2024

The structure of fibrinogen and resulting fibrin formed during the coagulation process have important biological functions in human physiology pathology. Fibrinogen post‐translational modifications (PTMs) increase complexity protein many studies emphasized potential associations post‐translationally altered with formation a clot prothrombotic phenotype. However, mechanisms by which PTMs exert their action on fibrinogen, causal association disease pathogenesis are relatively unexplored. Moreover, significance health has yet to be appreciated. In this review, impact functionality is discussed from biochemical perspective, emphasizing mediate acquisition properties. A brief discussion dysfibrinogenemias genetic origin, attributed single point variations molecule also provided, highlighting influence that amino acid properties structure, properties, molecular interactions arise thrombus formation.

Language: Английский

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TTLL12 has a potential oncogenic activity, suppression of ligation of nitrotyrosine to the C-terminus of detyrosinated α-tubulin, that can be overcome by molecules identified by screening a compound library

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(2), P. e0296960 - e0296960

Published: Feb. 23, 2024

Tubulin tyrosine ligase 12 (TTLL12) is a promising target for therapeutic intervention since it has been implicated in tumour progression, the innate immune response to viral infection, ciliogenesis and abnormal cell division. It most mysterious of fourteen-member TTL/TTLL family, since, although topmost conserved evolution, does not have predicted enzymatic activities. TTLL12 seems act as pseudo-enzyme that modulates various processes indirectly. Given need its functions, we initially set out identify property could be used develop reliable high-throughput screening assay. We discovered suppresses toxicity nitrotyrosine (3-nitrotyrosine) ligation C-terminus detyrosinated α-tubulin (abbreviated ligated-nitrotyrosine). Nitrotyrosine produced by oxidative stress associated with cancer progression. Ligation postulated check-point induced excessive stress. found cytotoxicities tubulin poisons are independent one another, suggesting drugs increase nitrotyrosination complementary current tubulin-directed therapeutics. suppression was robust cell-based ELISA assay detects increased cells overexpress adapted high throughput format screen 10,000 molecule World Biological Diversity SETTM collection low-molecular weight molecules. Two molecules were identified robustly activate at 1 μM concentration. This pioneer modulate α-tubulin. The from will useful study TTLL12, well leads development treat other pathologies involve nitrotyrosination.

Language: Английский

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Impact of Tyrosine Amination on the Aggregation and Neurotoxicity of Amyloid-Β: Unveiling a Potential Defensive Mechanism in Alzheimer's Disease

Published: Jan. 1, 2024

Language: Английский

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