Calcineurin B inhibits calcium oxalate crystallization, growth and aggregation via its high calcium-affinity property
Issued Date
2023-01-01
Resource Type
eISSN
20010370
Scopus ID
2-s2.0-85166735744
Journal Title
Computational and Structural Biotechnology Journal
Volume
21
Start Page
3854
End Page
3864
Rights Holder(s)
SCOPUS
Bibliographic Citation
Computational and Structural Biotechnology Journal Vol.21 (2023) , 3854-3864
Suggested Citation
Hadpech S., Chaiyarit S., Thongboonkerd V. Calcineurin B inhibits calcium oxalate crystallization, growth and aggregation via its high calcium-affinity property. Computational and Structural Biotechnology Journal Vol.21 (2023) , 3854-3864. 3864. doi:10.1016/j.csbj.2023.07.038 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/88303
Title
Calcineurin B inhibits calcium oxalate crystallization, growth and aggregation via its high calcium-affinity property
Author(s)
Author's Affiliation
Other Contributor(s)
Abstract
Calcineurin inhibitors (CNIs) are widely used in organ transplantation to suppress immunity and prevent allograft rejection. However, some transplant patients receiving CNIs have hypocitraturia, hyperoxaluria and kidney stone with unclear mechanism. We hypothesized that CNIs suppress activities of urinary calcineurin, which may serve as the stone inhibitor. This study aimed to investigate effects of calcineurin B (CNB) on calcium oxalate monohydrate (COM) stone formation. Sequence and structural analyses revealed that CNB contained four EF-hand (Ca2+-binding) domains, which are known to regulate Ca2+ homeostasis and likely to affect COM crystals. Various crystal assays revealed that CNB dramatically inhibited COM crystallization, crystal growth and crystal aggregation. At an equal amount, degrees of its inhibition against crystallization and crystal growth were slightly inferior to total urinary proteins (TUPs) from healthy subjects that are known to strongly inhibit COM stone formation. Surprisingly, its inhibitory effect against crystal aggregation was slightly superior to TUPs. While TUPs dramatically inhibited crystal-cell adhesion, CNB had no effect on this process. Ca2+-affinity assay revealed that CNB strongly bound Ca2+ at a comparable degree as of TUPs. These findings indicate that CNB serves as a novel inhibitor of COM crystallization, growth and aggregation via its high Ca2+-affinity property.