Discovery of Selenocysteine as a Potential Nanomedicine Promotes Cartilage Regeneration With Enhanced Immune Response by Text Mining and Biomedical Databases

Ye, Jing; Xu, Bingbing; Fan, Bao-Shi; Zhang, Jiying; Yuan, Fu‐Zhen; Chen, Yourong; Sun, Zewen; Yan, Xin; Song, Yifan; Song, Shitang; Yang, Meng; Yu, Jia‐Kuo

doi:10.3389/fphar.2020.01138

Cited by 5 publications

(3 citation statements)

References 62 publications

(64 reference statements)

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“…Here we have shown the mechanisms behind trafficking of SLC38A6 in the glutamate–glutamine cycle in neuronal cells. The trafficking mechanisms could be functioning in other cell types where SLC38A6 expression is found which includes pancreas [ 39 ], cartilage [ 40 ], circulatory tissue [ 41 ], etc.…”

Section: Discussionmentioning

confidence: 99%

Glutamine Uptake via SNAT6 and Caveolin Regulates Glutamine–Glutamate Cycle

Gandasi

Arapi

Mickael

et al. 2021

IJMS

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SLC38A6 (SNAT6) is the only known member of the SLC38 family that is expressed exclusively in the excitatory neurons of the brain. It has been described as an orphan transporter with an unknown substrate profile, therefore very little is known about SNAT6. In this study, we addressed the substrate specificity, mechanisms for internalization of SNAT6, and the regulatory role of SNAT6 with specific insights into the glutamate–glutamine cycle. We used tritium-labeled amino acids in order to demonstrate that SNAT6 is functioning as a glutamine and glutamate transporter. SNAT6 revealed seven predicted transmembrane segments in a homology model and was localized to caveolin rich sites at the plasma membrane. SNAT6 has high degree of specificity for glutamine and glutamate. Presence of these substrates enables formation of SNAT6-caveolin complexes that aids in sodium dependent trafficking of SNAT6 off the plasma membrane. To further understand its mode of action, several potential interacting partners of SNAT6 were identified using bioinformatics. Among them where CTP synthase 2 (CTPs2), phosphate activated glutaminase (Pag), and glutamate metabotropic receptor 2 (Grm2). Co-expression analysis, immunolabeling with co-localization analysis and proximity ligation assays of these three proteins with SNAT6 were performed to investigate possible interactions. SNAT6 can cycle between cytoplasm and plasma membrane depending on availability of substrates and interact with Pag, synaptophysin, CTPs2, and Grm2. Our data suggest a potential role of SNAT6 in glutamine uptake at the pre-synaptic terminal of excitatory neurons. We propose here a mechanistic model of SNAT6 trafficking that once internalized influences the glutamate–glutamine cycle in presence of its potential interacting partners.

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Section: Discussionmentioning

confidence: 99%

Glutamine Uptake via SNAT6 and Caveolin Regulates Glutamine–Glutamate Cycle

Gandasi

Arapi

Mickael

et al. 2021

IJMS

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“…Therefore, the tumor promotion effect of FAM20A may be accomplished through the activation of FAM20C. A recent study showed that FAM20A can be used as a prospective biomarker for the diagnosis and biomaterial drug therapy of cartilage lesions ( 83 ). FAM20A is involved in cartilage regeneration and mainly related to immune response and cell chemotaxis, thus can be used as the final nanomedicine immunotherapy in regenerative medicine ( 83 ).…”

Section: The Role Of the Secretory Pathway Kinases Or Kinase-like Pro...mentioning

confidence: 99%

Regulation of secretory pathway kinase or kinase-like proteins in human cancers

Zhu²,

Ren³

et al. 2023

Front. Immunol.

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Secretory pathway kinase or kinase-like proteins (SPKKPs) are effective in the lumen of the endoplasmic reticulum (ER), Golgi apparatus (GA), and extracellular space. These proteins are involved in secretory signaling pathways and are distinctive from typical protein kinases. Various reports have shown that SPKKPs regulate the tumorigenesis and progression of human cancer via the phosphorylation of various substrates, which is essential in physiological and pathological processes. Emerging evidence has revealed that the expression of SPKKPs in human cancers is regulated by multiple factors. This review summarizes the current understanding of the contribution of SPKKPs in tumorigenesis and the progression of immunity. With the epidemic trend of immunotherapy, targeting SPKKPs may be a novel approach to anticancer therapy. This study briefly discusses the recent advances regarding SPKKPs.

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“…Moreover, findings of a microarray analysis have revealed that medroxyprogesterone acetate (MPA), a progestin-based hormonal contraceptive designed to mimic progesterone, increases expression of genes related to inflammation and cholesterol synthesis, as well as those genes associated with both innate immunity and HIV-1 susceptibility [160]. Finally, integrative microarray data have been exploited to identify eight hub genes and one potential nanomedicinal drug, Selenocysteine, that promotes cartilage regeneration [161].…”

Section: Microarrays and Drug Discovery For Various Other Pathologiesmentioning

confidence: 99%

Microarrays and NGS for Drug Discovery

Pop¹,

Zănoagă²,

Chiroi³

et al. 2021

Drug Design - Novel Advances in the Omics Field and Applications

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Novel technologies and state of the art platforms developed and launched over the last two decades such as microarrays, next-generation sequencing, and droplet PCR have provided the medical field many opportunities to generate and analyze big data from the human genome, particularly of genomes altered by different diseases like cancer, cardiovascular, diabetes and obesity. This knowledge further serves for either new drug discovery or drug repositioning. Designing drugs for specific mutations and genotypes will dramatically modify a patient’s response to treatment. Among other altered mechanisms, drug resistance is of concern, particularly when there is no response to cancer therapy. Once these new platforms for omics data are in place, available information will be used to pursue precision medicine and to establish new therapeutic guidelines. Target identification for new drugs is necessary, and it is of great benefit for critical cases where no alternatives are available. While mutational status is of highest importance as some mutations can be pathogenic, screening of known compounds in different preclinical models offer new and quick strategies to find alternative frameworks for treating more diseases with limited therapeutic options.

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Discovery of Selenocysteine as a Potential Nanomedicine Promotes Cartilage Regeneration With Enhanced Immune Response by Text Mining and Biomedical Databases

Cited by 5 publications

References 62 publications

Glutamine Uptake via SNAT6 and Caveolin Regulates Glutamine–Glutamate Cycle

Glutamine Uptake via SNAT6 and Caveolin Regulates Glutamine–Glutamate Cycle

Regulation of secretory pathway kinase or kinase-like proteins in human cancers

Microarrays and NGS for Drug Discovery

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