Modulation of the thiol redox proteome by sugarcane ash-derived silica nanoparticles: insights into chronic kidney disease of unknown etiology
Abstract Introduction Chronic kidney disease of unknown etiology (CKDu) is an epidemic which is increasingly prevalent among agricultural workers and nearby communities, particularly those involved in the harvest of sugarcane. While CKDu is likely multifactorial, occupational exposure to silica nano...
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BMC
2025-02-01
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| Series: | Particle and Fibre Toxicology |
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| Online Access: | https://doi.org/10.1186/s12989-025-00619-8 |
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| author | Arthur D. Stem Cole R. Michel Peter S. Harris Keegan L. Rogers Matthew Gibb Carlos A. Roncal-Jimenez Richard Reisdorph Richard J. Johnson James R. Roede Kristofer S. Fritz Jared M. Brown |
| author_facet | Arthur D. Stem Cole R. Michel Peter S. Harris Keegan L. Rogers Matthew Gibb Carlos A. Roncal-Jimenez Richard Reisdorph Richard J. Johnson James R. Roede Kristofer S. Fritz Jared M. Brown |
| author_sort | Arthur D. Stem |
| collection | DOAJ |
| description | Abstract Introduction Chronic kidney disease of unknown etiology (CKDu) is an epidemic which is increasingly prevalent among agricultural workers and nearby communities, particularly those involved in the harvest of sugarcane. While CKDu is likely multifactorial, occupational exposure to silica nanoparticles (SiNPs), a major constituent within sugarcane ash, has gained increased attention as a potential contributor. SiNPs have high potential for generation of reactive oxygen species (ROS), and their accumulation in kidney could result in oxidative stress induced kidney damage consistent with CKDu pathology. Methods In order to characterize the impact of sugarcane ash derived (SAD) SiNPs on human kidney proximal convoluted tubule (PCT) cells and identify potential mechanisms of toxicity, HK-2 cells were exposed to treatments of either pristine, manufactured, 200 nm SiNPs or SAD SiNPs and changes to cellular energy metabolism and redox state were determined. To determine how the cellular redox environment may influence PCT cell function and toxicity, the redox proteome was examined using cysteine-targeted click chemistry proteomics. Results Pristine, 200 nm SiNPs induced minimal changes to energy metabolism and proteomic profiles in vitro while treatment with SAD SiNPs resulted in mitochondrial membrane hyperpolarization, inhibited mitochondrial respiration, increased reactive oxygen species generation, and redox proteomic trends suggesting activation of aryl hydrocarbon receptor (AHR) and other signaling pathways with known roles in mitochondrial inhibition and CKD progression. Conclusion Results suggest that PCT cell exposure to SAD SiNPs could promote glycolytic and fibrotic shifts consistent with CKDu pathology via oxidative stress-mediated disruption of redox signaling pathways. |
| format | Article |
| id | doaj-art-8d6b398337d14ad9b691bfd9d915d2e9 |
| institution | Kabale University |
| issn | 1743-8977 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Particle and Fibre Toxicology |
| spelling | doaj-art-8d6b398337d14ad9b691bfd9d915d2e92025-02-09T12:04:42ZengBMCParticle and Fibre Toxicology1743-89772025-02-0122112110.1186/s12989-025-00619-8Modulation of the thiol redox proteome by sugarcane ash-derived silica nanoparticles: insights into chronic kidney disease of unknown etiologyArthur D. Stem0Cole R. Michel1Peter S. Harris2Keegan L. Rogers3Matthew Gibb4Carlos A. Roncal-Jimenez5Richard Reisdorph6Richard J. Johnson7James R. Roede8Kristofer S. Fritz9Jared M. Brown10Department of Pharmaceutical Sciences, University of Colorado Anschutz CampusDepartment of Pharmaceutical Sciences, University of Colorado Anschutz CampusDepartment of Pharmaceutical Sciences, University of Colorado Anschutz CampusDepartment of Pharmaceutical Sciences, University of Colorado Anschutz CampusDepartment of Pharmaceutical Sciences, University of Colorado Anschutz CampusDivision of Renal Diseases and Hypertension, University of Colorado Anschutz Medical CampusDepartment of Pharmaceutical Sciences, University of Colorado Anschutz CampusDivision of Renal Diseases and Hypertension, University of Colorado Anschutz Medical CampusDepartment of Pharmaceutical Sciences, University of Colorado Anschutz CampusDepartment of Pharmaceutical Sciences, University of Colorado Anschutz CampusDepartment of Pharmaceutical Sciences, University of Colorado Anschutz CampusAbstract Introduction Chronic kidney disease of unknown etiology (CKDu) is an epidemic which is increasingly prevalent among agricultural workers and nearby communities, particularly those involved in the harvest of sugarcane. While CKDu is likely multifactorial, occupational exposure to silica nanoparticles (SiNPs), a major constituent within sugarcane ash, has gained increased attention as a potential contributor. SiNPs have high potential for generation of reactive oxygen species (ROS), and their accumulation in kidney could result in oxidative stress induced kidney damage consistent with CKDu pathology. Methods In order to characterize the impact of sugarcane ash derived (SAD) SiNPs on human kidney proximal convoluted tubule (PCT) cells and identify potential mechanisms of toxicity, HK-2 cells were exposed to treatments of either pristine, manufactured, 200 nm SiNPs or SAD SiNPs and changes to cellular energy metabolism and redox state were determined. To determine how the cellular redox environment may influence PCT cell function and toxicity, the redox proteome was examined using cysteine-targeted click chemistry proteomics. Results Pristine, 200 nm SiNPs induced minimal changes to energy metabolism and proteomic profiles in vitro while treatment with SAD SiNPs resulted in mitochondrial membrane hyperpolarization, inhibited mitochondrial respiration, increased reactive oxygen species generation, and redox proteomic trends suggesting activation of aryl hydrocarbon receptor (AHR) and other signaling pathways with known roles in mitochondrial inhibition and CKD progression. Conclusion Results suggest that PCT cell exposure to SAD SiNPs could promote glycolytic and fibrotic shifts consistent with CKDu pathology via oxidative stress-mediated disruption of redox signaling pathways.https://doi.org/10.1186/s12989-025-00619-8Chronic kidney disease of an unknown etiologyCKDuRedoxProteomicsAryl hydrocarbon receptorTGFβ |
| spellingShingle | Arthur D. Stem Cole R. Michel Peter S. Harris Keegan L. Rogers Matthew Gibb Carlos A. Roncal-Jimenez Richard Reisdorph Richard J. Johnson James R. Roede Kristofer S. Fritz Jared M. Brown Modulation of the thiol redox proteome by sugarcane ash-derived silica nanoparticles: insights into chronic kidney disease of unknown etiology Particle and Fibre Toxicology Chronic kidney disease of an unknown etiology CKDu Redox Proteomics Aryl hydrocarbon receptor TGFβ |
| title | Modulation of the thiol redox proteome by sugarcane ash-derived silica nanoparticles: insights into chronic kidney disease of unknown etiology |
| title_full | Modulation of the thiol redox proteome by sugarcane ash-derived silica nanoparticles: insights into chronic kidney disease of unknown etiology |
| title_fullStr | Modulation of the thiol redox proteome by sugarcane ash-derived silica nanoparticles: insights into chronic kidney disease of unknown etiology |
| title_full_unstemmed | Modulation of the thiol redox proteome by sugarcane ash-derived silica nanoparticles: insights into chronic kidney disease of unknown etiology |
| title_short | Modulation of the thiol redox proteome by sugarcane ash-derived silica nanoparticles: insights into chronic kidney disease of unknown etiology |
| title_sort | modulation of the thiol redox proteome by sugarcane ash derived silica nanoparticles insights into chronic kidney disease of unknown etiology |
| topic | Chronic kidney disease of an unknown etiology CKDu Redox Proteomics Aryl hydrocarbon receptor TGFβ |
| url | https://doi.org/10.1186/s12989-025-00619-8 |
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