Role of hemoglobin/heme scavenger protein hemopexin in atherosclerosis and inflammatory diseases

Mehta, Niyati; Reddy, Srinivasa T.

doi:10.1097/mol.0000000000000208

Cited by 36 publications

(28 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Hemopexin is a scavenger protein of haemoglobin and a predominant heme binding protein, which contributes to heme homeostasis (Smith and McCulloh, 2015;Immenschuh et al, 2017). Hemopexin also associates with high density lipoproteins (HDL), influencing their inflammatory properties (Mehta and Reddy, 2015). Hemopexin is a plasma glycoprotein that has been previously identified as a deimination candidate in teleost fish (Magnadóttir et al, 2019a) and shark (Criscitiello et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)—Novel insights into camelid immunity

Criscitiello

Kraev

Lange

2020

Molecular Immunology

View full text Add to dashboard Cite

A B S T R A C TPeptidylarginine deiminases (PADs) are phylogenetically conserved calcium-dependent enzymes which posttranslationally convert arginine into citrulline in target proteins in an irreversible manner, causing functional and structural changes in target proteins. Protein deimination causes generation of neo-epitopes, affects gene regulation and also allows for protein moonlighting. Furthermore, PADs have been found to be a phylogenetically conserved regulator for extracellular vesicle (EVs) release. EVs are found in most body fluids and participate in cellular communication via transfer of cargo proteins and genetic material. In this study, post-translationally deiminated proteins in serum and serum-EVs are described for the first time in camelids, using the llama (Lama glama L. 1758) as a model animal. We report a poly-dispersed population of llama serum EVs, positive for phylogenetically conserved EV-specific markers and characterised by TEM. In serum, 103 deiminated proteins were overall identified, including key immune and metabolic mediators including complement components, immunoglobulin-based nanobodies, adiponectin and heat shock proteins. In serum, 60 deiminated proteins were identified that were not in EVs, and 25 deiminated proteins were found to be unique to EVs, with 43 shared deiminated protein hits between both serum and EVs. Deiminated histone H3, a marker of neutrophil extracellular trap formation, was also detected in llama serum. PAD homologues were identified in llama serum by Western blotting, via cross reaction with human PAD antibodies, and detected at an expected 70 kDa size. This is the first report of deiminated proteins in serum and EVs of a camelid species, highlighting a hitherto unrecognized post-translational modification in key immune and metabolic proteins in camelids, which may be translatable to and inform a range of human metabolic and inflammatory pathologies.

show abstract

Section: Discussionmentioning

confidence: 99%

Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)—Novel insights into camelid immunity

Criscitiello

Kraev

Lange

2020

Molecular Immunology

View full text Add to dashboard Cite

show abstract

“…Two hemoglobin scavenger proteins such as HBB and HPX showed differential regulations from our findings were implicated with HDL and influence the inflammatory properties of HDL and scavenging of oxygen binding and transport from the lungs to the peripheral tissues and also involved in a number of inflammatory diseases (Newkirk et al, 1999). In addition, the depletion of HPX levels implicated in a number of inflammatory diseases such as septic shock and experimental autoimmune encephalomyelitis (Mehta et al, 2015). The primary function of HPX is heme scavenging and it protects against oxidative stress and related inflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

Peer Review #2 of "Plasma proteomic analysis of systemic lupus erythematosus patients using liquid chromatography/tandem mass spectrometry with label-free quantification (v0.1)"

2018

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with unknown etiology. Objective: Human plasma is comprised of over ten orders of magnitude concentration of proteins and tissue leakages. The changes in the abundance of these proteins have been playing an important role in various human diseases. Therefore, the research objective of this study is to identify the significantly altered expression levels of plasma proteins from SLE patients compared with healthy controls using proteomic analysis.The plasma proteome profiles of both SLE patients and controls were compared. Methods: 19 active SLE patients and 12 healthy controls plasma samples were analyzed using highresolution electrospray ionization liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) followed by label-free quantification. Results: Nineteen proteins showed a significant level of expression in the comparative LC-ESI-MS/MS triplicate analysis, among these, 14 proteins with > 1.5 to 3 fold upregulation and five with <0.2-0.6 fold down-regulation. GO and DAVID functional enrichment analysis revealed that these proteins involved in several important biological processes including acute phase inflammatory responses, complement activation, hemostasis, and immune system regulation. Conclusion: Our study identified a group of differentially expressed proteins in the plasma of SLE patients that are involved in the imbalance of the immune system and inflammatory responses. Therefore, these findings may have the potential to be used as prognostic/diagnostic markers for SLE disease assessment or disease monitoring.

show abstract

“…Several databases, such as GO (Fig S2), Nr, Swiss-Prot, Pfam, and KEGG, were searched for functional annotation of unigenes. In total, 56.78% (22,395) unigenes were annotated at least once in the databases searched (Table 2). Furthermore, 16,754 unigenes ≥1,000 nt in length were annotated by the different databases.…”

Section: Gene Function Annotation and Cds Prediction Of Unigenesmentioning

confidence: 99%

Transcriptome Analysis of the Liver of Eospalax Fontanierii Under Hypoxia

Hao

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundHypoxia can induce cell damage, inflammation, carcinogenesis, and inhibit liver regeneration in non-adapted species. Because of their excellent hypoxia adaptation features, subterranean rodents have been widely studied to clarify the mechanism of hypoxia adaptation. Eospalax fontanierii, which is a subterranean rodent found in China, can survive for more than 10 h under 4% O2 without observable injury, while Sprague-Dawle rats can survive for less than 6 h under the same conditions. To explore the potential mechanism of hypoxia adaptation in E. fontanierii, we performed RNA-seq analysis of the liver in E. fontanierii exposed to different oxygen levels (6.5%, 10.5%, and 21%).ResultsBased on the bioinformatics analysis, 39,439 unigenes were assembled, and 56.78% unigenes were annotated using public databases (Nr, GO, Swiss-Prot, KEGG, and Pfam). In total, 725 differentially expressed genes (DEGs) were identified in the response to hypoxia; six with important functions were validated by qPCR. Those DEGs were mainly involved in processes related to lipid metabolism, steroid catabolism, glycolysis/gluconeogenesis, and the AMPK and PPAR signaling pathway. By analyzing the expression patterns of hub genes related to energy associated metabolism under hypoxia, we found that fatty acid oxidation and gluconeogenesis were increased, while protein synthesis and fatty acid synthesis were decreased. ConclusionsWe characterized the E. fontanierii liver transcriptomes and profiled the changes in gene expression in the liver under different oxygen levels. Functional enrichment analysis showed that the main functions (steroid catabolic process, lipid metabolic process, primary bile acid biosynthesis, energy production and amino acid metabolic) of the liver were regulated in response to hypoxia. We identified multiple important DEGs underlying the potential molecular adaptation mechanisms to hypoxia, including genes associated with anti-apoptosis, energy supply, anti-inflammation, and anti-oxidation. Our results provide a comprehensive understanding of the response to hypoxia in E. fontanierii, and have potential value for biomedical studies.

show abstract

Role of hemoglobin/heme scavenger protein hemopexin in atherosclerosis and inflammatory diseases

Cited by 36 publications

References 28 publications

Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)—Novel insights into camelid immunity

Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)—Novel insights into camelid immunity

Peer Review #2 of "Plasma proteomic analysis of systemic lupus erythematosus patients using liquid chromatography/tandem mass spectrometry with label-free quantification (v0.1)"

Transcriptome Analysis of the Liver of Eospalax Fontanierii Under Hypoxia

Contact Info

Product

Resources

About