Myoglobin: From physiological roles to potential implications in cancer

Elkholi, Islam; Elsherbiny, Marwa E.; Emara, Marwan

doi:10.1016/j.bbcan.2022.188706

Cited by 14 publications

(12 citation statements)

References 122 publications

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“…Mixed expression of SYNM has also been noted in hepatobiliary cancer, with upregulation in cholangiocarcinoma cells and absence in hepatocellular cells 23 . Ectopic myoglobin, expressed outside of muscle, has been noted in epithelial tumours and head and neck SCCs (HNSCCs), and myoglobin expression in the tumours is associated with a better prognosis 24,25 . Myoglobin can occur from hypoxia‐induced tumour transcript variants but also in non‐hypoxic settings with a proposed scavenger function to reduce reactive oxygen species 24 .…”

Section: Discussionmentioning

confidence: 99%

“…23 Ectopic myoglobin, expressed outside of muscle, has been noted in epithelial tumours and head and neck SCCs (HNSCCs), and myoglobin expression in the tumours is associated with a better prognosis. 24,25 Myoglobin can occur from hypoxia-induced tumour transcript variants but also in non-hypoxic settings with a proposed scavenger function to reduce reactive oxygen species. 24 FBLN1 is a tumour suppressor gene known to be downregulated in multiple cancers via hypermethylation, including tongue SCCs, where 5-Aza-dC-induced demethylation suppressed tongue SCC cell proliferation, migration and invasion.…”

Section: Olp (Indolent and Transforming) Versus Nommentioning

confidence: 99%

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Differential proteomic expression in indolent versus transforming oral lichen planus

Xie

Gleue

Deschaine

et al. 2023

Experimental Dermatology

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Oral lichen planus (OLP) confers an approximately 1% risk of transformation to oral squamous cell carcinoma (OSCC). Early identification of high‐risk OLP would be very helpful for optimal patient management. We aimed to discover specific tissue‐based protein biomarkers in patients with OLP who developed OSCC compared to those who did not. We used laser capture microdissection– and nanoLC–tandem mass spectrometry to assess protein expression in fixed lesional mucosal specimens in patients with indolent OLP (no OSCC after at least 5‐year follow‐up, n = 6), transforming OLP (non‐dysplastic epithelium with lichenoid inflammation marginal to OSCC, n = 6) or normal oral mucosa (NOM, n = 5). Transforming OLP protein profile was enriched for actin cytoskeleton, mitochondrial dysfunction and oxidative phosphorylation pathways. CA1, TNNT3, SYNM and MB were overexpressed, and FBLN1 was underexpressed in transforming OLP compared with indolent OLP. Integrin signalling and antigen presentation pathways were enriched in both indolent and transforming OLP compared with NOM. This proteomic study provides potential biomarkers, such as CA1 overexpression, for higher‐risk OLP. While further validation studies are needed, we propose that epithelial–mesenchymal transition may be involved in OLP carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Olp (Indolent and Transforming) Versus Nommentioning

confidence: 99%

Differential proteomic expression in indolent versus transforming oral lichen planus

Xie

Gleue

Deschaine

et al. 2023

Experimental Dermatology

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“…The complete process has been alluded to as reductive sulfhydration, , after the well-described reductive nitrosylation. In this sense, anaerobic studies of the reductive nitrosylation reaction of hemes and hemeproteins have proven valuable in shedding light on the mechanistic description of the process. , Also, the insight into the reaction under an anaerobic atmosphere may assist in the interpretation of biochemical aspects of ectopic myoglobins found in hypoxic tissues . The reaction conditions selected in this work allowed the complete reduction of MbFe III to MbFe II following a pH-dependent autocatalytic route, with the participation of ferric heme iron as a unique one-electron oxidant for inorganic sulfide.…”

Section: Introductionmentioning

confidence: 99%

Autocatalytic Mechanism in the Anaerobic Reduction of Metmyoglobin by Sulfide Species

et al. 2023

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The mechanism of the metal centered reduction of metmyoglobin (MbFe III ) by sulfide species (H 2 S/HS − ) under an argon atmosphere has been studied by a combination of spectroscopic, kinetic, and computational methods. Asymmetric Sshaped time-traces for the formation of MbFe II at varying ratios of excess sulfide were observed at pH 5.3 < pH < 8.0 and 25 °C, suggesting an autocatalytic reaction mechanism. An increased rate at more alkaline pHs points to HS − as relevant reactive species for the reduction. The formation of the sulfanyl radical (HS • ) in the slow initial phase was assessed using the spin-trap phenyl N-tert-butyl nitrone. This radical initiates the formation of S−S reactive species as disulfanuidyl/ disulfanudi-idyl radical anions and disulfide (HSSH •− /HSS •2− and HSS − , respectively). The autocatalysis has been ascribed to HSS − , formed after HSSH •− /HSS •2− disproportionation, which behaves as a fast reductant toward the intermediate complex MbFe III (HS − ). We propose a reaction mechanism for the sulfide-mediated reduction of metmyoglobin where only ferric heme iron initiates the oxidation of sulfide species. Beside the chemical interest, this insight into the MbFe III / sulfide reaction under an argon atmosphere is relevant for the interpretation of biochemical aspects of ectopic myoglobins found on hypoxic tissues toward reactive sulfur species.

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“…The quantification of metal–ligand bonding in proteins is of paramount importance for a deeper understanding of biochemical processes . As an example, heme proteins such as myoglobin (Mb) and neuroglobin (Ngb), , both members of the globin superfamily of proteins, , share a comparable active site with a prosthetic heme group consisting of a protoporphyrin ring with a central iron core, which is attached to the protein backbone via the proximal histidine. Signaling ligands L such as CO, NO, O 2 , H 2 S coordinate to the Fe on the opposite site of the porphyrin ring interacting with the distal histidine.…”

Section: Resultsmentioning

confidence: 99%

The Local Vibrational Mode Theory and Its Place in the Vibrational Spectroscopy Arena

et al. 2022

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This Feature Article starts highlighting some recent experimental and theoretical advances in the field of IR and Raman spectroscopy, giving a taste of the breadth and dynamics of this striving field. The local mode theory is then reviewed, showing how local vibrational modes are derived from fundamental normal modes. New features are introduced that add to current theoretical efforts: (i) a unique measure of bond strength based on local mode force constants ranging from bonding in single molecules in different environments to bonding in periodic systems and crystals and (ii) a new way to interpret vibrational spectra by pinpointing and probing interactions between particular bond stretching contributions to the normal modes. All of this represents a means to work around the very nature of normal modes, namely that the vibrational motions in polyatomic molecules are delocalized. Three current focus points of the local mode analysis are reported, demonstrating how the local mode analysis extracts important information hidden in vibrational spectroscopy data supporting current experiments: (i) metal−ligand bonding in heme proteins, such as myoglobin and neuroglobin; (ii) disentanglement of DNA normal modes; and (iii) hydrogen bonding in water clusters and ice. Finally, the use of the local mode analysis by other research groups is summarized. Our vision is that in the future local mode analysis will be routinely applied by the community and that this Feature Article serves as an incubator for future collaborations between experiment and theory.

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Myoglobin: From physiological roles to potential implications in cancer

Cited by 14 publications

References 122 publications

Differential proteomic expression in indolent versus transforming oral lichen planus

Differential proteomic expression in indolent versus transforming oral lichen planus

Autocatalytic Mechanism in the Anaerobic Reduction of Metmyoglobin by Sulfide Species

The Local Vibrational Mode Theory and Its Place in the Vibrational Spectroscopy Arena

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