ArticleBMC biotechnology2018
Phenotype-specific recombinant haptoglobin polymers co-expressed with C1r-like protein as optimized hemoglobin-binding therapeutics.
Article in BMC biotechnology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 27 citations in OpenAlex.
- Identification of proteomic markers of chronic prostatitis/chronic pelvic pain syndrome treated with melatonin using a tandem mass tag approach.Current urology · 2025Article
- An anoikis-related gene signature predicts prognosis, drug sensitivity, and immune microenvironment in cholangiocarcinoma.Heliyon · 2024Article
- Haptoglobin Treatment for Aneurysmal Subarachnoid Hemorrhage: Review and Expert Consensus on Clinical Translation.Stroke · 2023Review
- Zonulin as a Potential Therapeutic Target in Microbiota-Gut-Brain Axis Disorders: Encouraging Results and Emerging Questions.International journal of molecular sciences · 2023Review
- Haptoglobin 1 allele predicts higher serum haptoglobin concentration and lower multiorgan failure risk in sickle cell disease.Blood advances · 2022Article
- Article
- Haptoglobin polymorphism affects its N-glycosylation pattern in serum.Journal of mass spectrometry and advances in the clinical lab · 2022Article
- Review
- Haptoglobin as a Biomarker.Biochemistry (Moscow) Supplement. Series B, Biomedical chemistry · 2021Article
- Inflammation and Oxidative Stress: Potential Targets for Improving Prognosis After Subarachnoid Hemorrhage.Frontiers in cellular neuroscience · 2021Review
- A wealth of genotype-specific proteoforms fine-tunes hemoglobin scavenging by haptoglobin.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPreclinical studies have evaluated haptoglobin (Hp) polymers from pooled human plasma as a therapeutic protein to attenuate toxic effects of cell-free hemoglobin (Hb). Proof of concept studies have demonstrated efficacy of Hp in hemolysis associated with transfusion and sickle cell anemia. However, phenotype-specific Hp products might be desirable to exploit phenotype specific activities of Hp 1-1 versus Hp 2-2, offering opportunities for recombinant therapeutics. Prohaptoglobin (proHp) is the primary translation product of the Hp mRNA. ProHp is proteolytically cleaved by complement C1r subcomponent-like protein (C1r-LP) in the endoplasmic reticulum. Two main allelic Hp variants, HP1 and HP2 exist. The larger HP2 is considered to be the ancestor variant of all human Hp alleles and is characterized by an α2-chain, which contains an extra cysteine residue that pairs with additional α-chains generating multimers with molecular weights of 200-900 kDa. The two human HP1 alleles (HP1F and HP1S) differ by a two-amino-acid substitution polymorphism within the α-chain and are derived from HP2 by recurring exon deletions.
resultsIn the present study, we describe a process for the production of recombinant phenotype specific Hp polymers in mammalian FS293F cells. This approach demonstrates that efficient expression of mature and fully functional protein products requires co-expression of active C1r-LP. The functional characterization of our proteins, which included monomer/polymer distribution, binding affinities as well as NO-sparing and antioxidant functions, demonstrated that C1r-LP-processed recombinant Hp demonstrates equal protective functions as plasma derived Hp in vitro as well as in animal studies.
conclusionsWe present a recombinant production process for fully functional phenotype-specific Hp therapeutics. The proposed process could accelerate the development of Hb scavengers to treat patients with cell-free Hb associated disease states, such as sickle cell disease and other hemolytic conditions.
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