Caffeine causes cell cycle arrest at G0/G1 and increases of ubiquitinated proteins, ATP and mitochondrial membrane potential in renal cells
Issued Date
2023-01-01
Resource Type
eISSN
20010370
Scopus ID
2-s2.0-85171976692
Journal Title
Computational and Structural Biotechnology Journal
Volume
21
Start Page
4552
End Page
4566
Rights Holder(s)
SCOPUS
Bibliographic Citation
Computational and Structural Biotechnology Journal Vol.21 (2023) , 4552-4566
Suggested Citation
Kanlaya R., Subkod C., Nanthawuttiphan S., Thongboonkerd V. Caffeine causes cell cycle arrest at G0/G1 and increases of ubiquitinated proteins, ATP and mitochondrial membrane potential in renal cells. Computational and Structural Biotechnology Journal Vol.21 (2023) , 4552-4566. 4566. doi:10.1016/j.csbj.2023.09.023 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/90270
Title
Caffeine causes cell cycle arrest at G0/G1 and increases of ubiquitinated proteins, ATP and mitochondrial membrane potential in renal cells
Author's Affiliation
Other Contributor(s)
Abstract
Caffeine is a well-known purine alkaloid commonly found in coffee. Several lines of previous and recent evidence have shown that habitual coffee drinking is associated with lower risks for chronic kidney disease (CKD) and nephrolithiasis. However, cellular and molecular mechanisms underlying its renoprotective effects remain largely unknown due to a lack of knowledge on cellular adaptive response to caffeine. This study investigated cellular adaptive response of renal tubular cells to caffeine at the protein level. Cellular proteome of MDCK cells treated with caffeine at a physiologic concentration (100 μM) for 24 h was analyzed comparing with that of untreated cells by label-free quantitative proteomics. From a total of 936 proteins identified, comparative analysis revealed significant changes in levels of 148 proteins induced by caffeine. These significantly altered proteins were involved mainly in proteasome, ribosome, tricarboxylic acid (TCA) (or Krebs) cycle, DNA replication, spliceosome, biosynthesis of amino acid, carbon metabolism, nucleocytoplasmic transport, cell cycle, cytoplasmic translation, translation initiation, and mRNA metabolic process. Functional validation by various assays confirmed that caffeine decreased cell population at G2/M, increased cell population at G0/G1, increased level of ubiquitinated proteins, increased intracellular ATP and enhanced mitochondrial membrane potential in MDCK cells. These data may help unravelling molecular mechanisms underlying the biological effects of caffeine on renal tubular cells at cellular and protein levels.