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The Challenge of Parasite Control
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2015
Eric S. Loker, Bruce V. Hofkin
One such candidate targets a protein found on the surface of P. falciparum called Plasmodium falciparum reticulocyte binding protein homolog 5 (PfRH5). P. falciparum is notorious for using a variety of receptor–ligand interactions to gain access to erythrocytes, and until now, none of these interactions were known to be required by all parasite strains. However, PfRH5, which binds a protein called basigin on erythrocytes, apparently is essential for merozoites of all strains investigated to date. Early trials have shown that merozoite invasion of erythrocytes can be completely blocked by neutralizing antibodies and that unlike other potential targets on blood-stage parasites, PfRH5 appears to have little diversity. Researchers have indicated that barring unforeseen problems, clinical trials with an anti-PfRH5 candidate vaccine could begin within a few years.
An Overview of Parasite Diversity
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
Also, by comparing multiple genomes from related parasites and searching for differences among them, we can begin to understand what makes each parasite species distinctive, allowing us to glimpse how knowledge of genomes leads to ever deeper insights into the specific mechanisms underpinning host-parasite interactions. For instance, let’s consider once again the question of the origin of the human parasite P. falciparum from related parasites found in gorillas. Sequences obtained for several related Plasmodium species infecting our great ape cousins are remarkably similar, but some diverging genes have been identified. One such gene rh5, encodes a protein involved in attaching malaria parasites to a protein called basigin on the surface of human erythrocytes (Figure 2.36), an essential feature in infectivity. By comparing rh5 sequences across Plasmodium species from different apes, it was possible to infer an ancestral state for this gene, one that encoded a version of the protein able to bind both human and gorilla erythrocytes. By systematically mutating bases at six key sites differentiating the ancestral and human forms of rh5, it was possible to identify a single amino acid mutation (H200Y) that was responsible for the production of a version of the RH5 protein able to bind human but not gorilla erythrocytes. Thus, scanning entire genomes, each of approximately 23Mbp, helped locate key genomic differences that pinpointed a particular gene, a single mutation of which can help account for the emergence of one of the deadliest infectious diseases of humanity, P. falciparum.
The S100A7/8/9 Proteins: Novel Biomarker and Therapeutic Targets for Solid Tumor Stroma
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Sanjay Mishra, Dinesh Ahirwar, Mohd W. Nasser, Ramesh K. Ganju
In melanoma patients, immune-based antibody drug ipilimumab treatment response has been shown to be positively associated with increase in eosinophil count and negatively associated with elevated amounts of MDSC and monocytes as compared with basal levels and with responding patients. It was also observed that ipilimumab treatment in non-responders resulted in elevated serum concentrations of S100A8/A9 and HMGB1 that attract and activate MDSCs [88]. In another study, S100A8 levels were found to be associated with clinical response rate in acute myeloblastic leukemia (AML). Knockdown of S100A8 increases autophagy and chemotherapy-induced cytotoxicity in AML cells. In addition, S100A8 directly regulates autophagy protein Beclin 1 and dissociates Beclin1-Bcl-2 complex [89, 90]. In search for novel S100 protein receptors, by using affinity isolation-mass spectrometry, cell surface glycoprotein EMMPRIN/BASIGIN (CD147/BSG) was identified as specific receptor to S100A9, which does not bind to S100A8. It was found that besides RAGE, S100A9 interacts with EMMPRIN to activate TNF receptor-associated factor TRAF2 and induce cytokines and metalloproteases expression [91]. Immunohistochemistry analysis revealed that EMMPRIN was expressed at the edge of melanoma lesion and adjacent epidermis and co-localize with S100A9 [91]. Similarly, ALCAM and MCAM molecules were identified as novel receptors for S100A8/A9 and induce melanoma progression by activating ROS production and NF-κB activation [92]. ß-1,3-galactosyl-O-glycosyl-glycoprotein ß-1,6-N-acetylglucosaminyltransferase 3 (GCNT3) has been shown to be overexpressed in metastatic melanomas. Molecular inhibition of GCNT3 resulted in reduced migration and invasion of melanoma cells, mediated by loss of S100A8/A9 signaling [93].
Considerations of the effects of commonly investigated drugs for COVID-19 in the cholesterol synthesis pathway
Published in Expert Opinion on Pharmacotherapy, 2021
Juan Luis Gomez Marti, Adam M. Brufsky
Basigin (CD147) and Cyclophilin A (CyPA) are membrane receptors used by SARS-CoV. Basigin is a transmembrane glycosylated immunoglobulin and principal receptor of extracellular cyclophilins. Cyclophilins are a family of ubiquitously distributed chemotactic agents that mediate intracellular trafficking and signal conduction. These are released extracellularly during an inflammatory response and commonly exhibited by dying cells. CyPA is the most abundant cyclophilin isoform. The chemotactic effects of CyPA take place primarily after binding to the extracellular domain of basigin. Downstream signaling catalyzes matrix metalloprotease (MMP) release, facilitating leukocyte recruitment [7]. Basigin acts as a receptor for several viruses including measles, HIV-1 and SARS-CoV [8]. Viral binding to basigin induces CyP binding to the N protein of SARS-CoV virions, permitting cellular entry [9]. A preprint of preliminary results in a clinical trial has shown an association between anti-basigin antibodies and decreased hospitalization length and disease severity [10].
Surface markers of human embryonic stem cells: a meta analysis of membrane proteomics reports
Published in Expert Review of Proteomics, 2018
Faezeh Shekari, Chia-Li Han, Jaesuk Lee, Mehdi Mirzaei, Vivek Gupta, Paul A. Haynes, Bonghee Lee, Hossein Baharvand, Yu-Ju Chen, Ghasem Hosseini Salekdeh
The function of these proteins in hESCs has not been reported; however, most are proliferation-related proteins in other cells. A close correlation between solute carrier family 7 member 5 (SLC7A5 or LAT-1) expression and cell proliferation has been shown [119]. For example, after binding to progesterone, progesterone receptor membrane component 1 (PGRMC1) can localize to the cytoplasm to elevate cell responsiveness to the anti-apoptotic action of progesterone [120]. However, PGRMC1 that is not bound to progesterone has the opposite effect in the nucleus by regulating gene expression on behalf of apoptosis [120]. Reticulon 4 (RTN4) regulates apoptosis and tumor development [121]. Cytoskeleton-associated protein 4 (CKAP4 or p63) is involved in the regulation of cancer stem cell metabolism [122]. It has been shown that calnexin enhances the STAT3-mediated transcriptional response to EGF [123]. Basigin (BSG or CD147) is a multifunctional protein that plays key roles in both normal tissue remodeling and cancer microenvironment regulation [124]. A panel of 22 candidate marker proteins in pluripotent cells was developed, including BSG [125].
Clinical significance of the CD98hc-CD147 complex in ovarian cancer: a bioinformatics analysis
Published in Journal of Obstetrics and Gynaecology, 2023
Xin-Yue Zhou, Jin-Yao Li, Jing-Tong Tan, Yi-Li HuangLi, Xiao-Cui Nie, Pu Xia
CD98 is a type II transmembrane glycoprotein with a size of approximately 85 kDa (Ip and Sethi 2016). It consists of a heavy chain (CD98 heavy chain [CD98hc, SLC3A2]) and a light chain (LAT1, LAT2, XCT, y + LAT1, y + LAT2, or ASC1) covalently linked by disulphide bonds to form a heterodimer (Ip and Sethi 2016). The CD98 protein promotes tumorigenesis and metastasis by regulating cell adhesion and extracellular matrix synthesis (Cano-Crespo et al. 2019). Moreover, SLC3A2/LAT1 mediates the transport of most neutral and aromatic amino acids and provides nutrients for cell metabolism (Scalise et al. 2020). Previous studies have shown that CD98hc is highly expressed in tumour tissues and suggests a poor prognosis. Moreover, its high expression is related to tumour development, progression, and migration (Kaira et al. 2014, Satoh et al. 2017, El Ansari et al. 2018). CD147 (basigin, BSG) is a single transmembrane glycoprotein, belonging to the immunoglobulin superfamily (de la Cruz Concepción et al. 2022). This gene is highly expressed in a variety of malignancies, and its high expression is an indicator of poor clinical prognosis (Chu et al. 2014, Liu et al. 2017, Zhang et al. 2022). Moreover, CD147 can be used as both an inducer and an effector to promote the growth, metabolism, invasion, metastasis, angiogenesis, drug resistance, death resistance, and other malignant behaviours of tumour cells through various mechanisms, leading to tumour progression (de la Cruz Concepción et al. 2022). Together, CD147 and CD98hc form the CD98hc-CD147 complex to further regulate the sugar and amino acid metabolism of cells (Xu and Hemler 2005). In this study, we aimed to clarify the clinicopathological and prognostic significance of the CD98hc-CD147 complex in ovarian cancer using bioinformatics analysis.