Non-Nitrogen-Containing Bisphosphonates Prevent Pyrophosphorylation of Exocytosis Proteins

Background: Clodronate, a non-nitrogen-containing bisphosphonate (non-NBP), is intracel-lularly converted into non-hydrolyzable ATP analogs. Clodronate and its analogs impair normal cell functions, including the exocytosis process. However, how this occurs in mast cells is still not well characteriz...

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Main Author: Sahid, Muhammad N. A.
Format: Article
Language:English
Published: Bentham Science Publishers 2022
Subjects:
Online Access:https://repository.ugm.ac.id/283666/1/Non-Nitrogen-Containing%20Bisphosphonates%20Prevent%20Pyrophosphorylation%20of%20Exocytosis%20Proteins.pdf
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author Sahid, Muhammad N. A.
author_facet Sahid, Muhammad N. A.
author_sort Sahid, Muhammad N. A.
collection UGM
description Background: Clodronate, a non-nitrogen-containing bisphosphonate (non-NBP), is intracel-lularly converted into non-hydrolyzable ATP analogs. Clodronate and its analogs impair normal cell functions, including the exocytosis process. However, how this occurs in mast cells is still not well characterized. Objective: To summarize the possible mechanisms of clodronate-mediated exocytosis inhibition in mast cells. Results: Non-NBPs display several possible mechanisms of exocytosis inhibition in various cell types, including vesicular nucleotide transporter (VNUT) and purinergic receptor inhibition. Inhibition of pu-rinergic receptors has been shown in mast cells, but VNUT inhibition remains to be confirmed. Inhibition of protein prenylation by non-NBPs has also been shown; however, direct evidence of non-NBPs in prenylated exocytosis proteins is still contradictory. Finally, non-NBPs may inhibit mast cell exocytosis via impairment of protein pyrophosphorylation. This mechanism is less studied, and direct evidence of the involvement of pyrophosphorylated proteins in exocytosis is still lacking. Conclusion: Non-NBPs may affect mast cell exocytosis by interacting with purinergic receptors or VNUT or by preventing post-translational modifications of exocytosis protein(s), i.e., prenylation and pyrophosphorylation. The latter needs further investigation to provide direct evidence of a role for non-NBPs. © 2022 Bentham Science Publishers.
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spelling oai:generic.eprints.org:2836662023-11-22T00:46:45Z https://repository.ugm.ac.id/283666/ Non-Nitrogen-Containing Bisphosphonates Prevent Pyrophosphorylation of Exocytosis Proteins Sahid, Muhammad N. A. Pharmaceutical Sciences Background: Clodronate, a non-nitrogen-containing bisphosphonate (non-NBP), is intracel-lularly converted into non-hydrolyzable ATP analogs. Clodronate and its analogs impair normal cell functions, including the exocytosis process. However, how this occurs in mast cells is still not well characterized. Objective: To summarize the possible mechanisms of clodronate-mediated exocytosis inhibition in mast cells. Results: Non-NBPs display several possible mechanisms of exocytosis inhibition in various cell types, including vesicular nucleotide transporter (VNUT) and purinergic receptor inhibition. Inhibition of pu-rinergic receptors has been shown in mast cells, but VNUT inhibition remains to be confirmed. Inhibition of protein prenylation by non-NBPs has also been shown; however, direct evidence of non-NBPs in prenylated exocytosis proteins is still contradictory. Finally, non-NBPs may inhibit mast cell exocytosis via impairment of protein pyrophosphorylation. This mechanism is less studied, and direct evidence of the involvement of pyrophosphorylated proteins in exocytosis is still lacking. Conclusion: Non-NBPs may affect mast cell exocytosis by interacting with purinergic receptors or VNUT or by preventing post-translational modifications of exocytosis protein(s), i.e., prenylation and pyrophosphorylation. The latter needs further investigation to provide direct evidence of a role for non-NBPs. © 2022 Bentham Science Publishers. Bentham Science Publishers 2022 Article PeerReviewed application/pdf en https://repository.ugm.ac.id/283666/1/Non-Nitrogen-Containing%20Bisphosphonates%20Prevent%20Pyrophosphorylation%20of%20Exocytosis%20Proteins.pdf Sahid, Muhammad N. A. (2022) Non-Nitrogen-Containing Bisphosphonates Prevent Pyrophosphorylation of Exocytosis Proteins. Current Protein and Peptide Science, 23 (8). 505 – 509. ISSN 13892037 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85141509070&doi=10.2174%2f1389203723666220620164024&partnerID=40&md5=848db6cb1fb7fa13bfcb448636bd90f5
spellingShingle Pharmaceutical Sciences
Sahid, Muhammad N. A.
Non-Nitrogen-Containing Bisphosphonates Prevent Pyrophosphorylation of Exocytosis Proteins
title Non-Nitrogen-Containing Bisphosphonates Prevent Pyrophosphorylation of Exocytosis Proteins
title_full Non-Nitrogen-Containing Bisphosphonates Prevent Pyrophosphorylation of Exocytosis Proteins
title_fullStr Non-Nitrogen-Containing Bisphosphonates Prevent Pyrophosphorylation of Exocytosis Proteins
title_full_unstemmed Non-Nitrogen-Containing Bisphosphonates Prevent Pyrophosphorylation of Exocytosis Proteins
title_short Non-Nitrogen-Containing Bisphosphonates Prevent Pyrophosphorylation of Exocytosis Proteins
title_sort non nitrogen containing bisphosphonates prevent pyrophosphorylation of exocytosis proteins
topic Pharmaceutical Sciences
url https://repository.ugm.ac.id/283666/1/Non-Nitrogen-Containing%20Bisphosphonates%20Prevent%20Pyrophosphorylation%20of%20Exocytosis%20Proteins.pdf
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