An integrated proteomic and phosphoproteomic landscape of chronic kidney disease DOI Creative Commons
Linxiao Sun, Cheng Wang, Zhongjing Zhou

et al.

Journal of Proteomics, Journal Year: 2024, Volume and Issue: 311, P. 105355 - 105355

Published: Nov. 14, 2024

The prevalence of chronic kidney disease (CKD) is gradually rising worldwide. Patients often remain asymptomatic for an extended period, leaving them unaware their condition, which can lead to progressing end-stage renal and cause significant economic burden. Improved understanding CKD pathogenesis enhance early detection facilitate advances in drug development. Here, we performed proteomic phosphoproteomic analyses the mouse unilateral ureteral obstruction model explore molecular mechanisms injury. 474 significantly differentially expressed proteins 96 phosphoproteins were screened, respectively. Chronic injury involves complex metabolic pathways such as citrate cycle hematopoietic system proteome, mitochondrial oxidative phosphorylation suppression a notable alteration. analysis revealed upregulation epithelial mesenchymal transition P53 pathways, with corresponding increase Jun at serine 73. Utilizing HK2 cells, observed that reduction was consistently associated augmentation stress, subsequently activated induced apoptosis. Proteins act hubs these may be candidate targets intervention. These findings contribute current provide valuable insights future studies. SIGNIFICANCE: incidence annually varied etiologies, irreversibly fibrotic, treatment options are limited ineffective due deficient fibrosis mechanisms. Despite extensive efforts numerous omics studies conducted on fibrosis, date, no study has been undertaken investigate role phosphorylated UUO models. Previously, comprehensive transcriptome proteome based model, but potential alterations phosphoproteome not addressed. integrated landscape completed, first profiles model. Phosphoproteomic profile suggests models injury, core protein played key CKD. And preliminary correlation between P-Jun found base cells. Our work contributes deeper characteristics Identifying from diagnosis

Language: Английский

Toward Real-Time Proteomics: Blood to Biomarker Quantitation in under One Hour DOI

Steven M. Yannone,

Vikas Tuteja,

Olena Goleva

et al.

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Multistep multihour tryptic proteolysis has limited the utility of bottom-up proteomics for cases that require immediate quantitative information. The power to quantify biomarkers health status cannot practically assist in clinical care if dynamics disease outpaces turnaround analysis. recently available hyperthermoacidic archaeal (HTA) protease "Krakatoa" digests samples a single 5 30 min step at pH 3 and >80 °C conditions disrupt most cells tissues, denature proteins, block disulfide reformation thereby dramatically expediting simplifying sample preparation. combination quick single-step with high-throughput dual-trapping analytical column (DTSC) liquid chromatography–mass spectrometry (LC–MS) returns actionable data less than 1 h from collection unprocessed biofluid. systematic evaluation this methodology finds over 160 proteins are quantified μL whole blood. Furthermore, labile Angiotensin I II bioactive peptides along panel protein species can be measured 8 intervals 20 initial lag using targeted MS. With these methods, we analyzed serum plasma 53 individuals 150 including least 46 were not detected trypsin. We discuss some implications real-time potential advance several research applications.

Language: Английский

Citations

0
Cross‐Species Molecular Similarities Based on Omics Approaches in CKD: Toward Improved Translation From Pre‐Clinical Models to Humans DOI
Raquel Garcia-Sáez, Mariano Rodríguez

PROTEOMICS, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

ABSTRACT The prevalence of chronic kidney disease (CKD) is very high, and it increasing. Obviously, the care costly. identification biomarkers able to predict progression key for optimal patient care. Tissue, blood, urine omics are being used discover new biomarkers. It challenging compare in animal models with that CKD patients. main obstacle enormous genetic difference between humans rodents. Although do not fully resemble CKD, there possibilities combine pathologies an attempt be closer human clinical picture. This manuscript describes Zucker rat model has been modified better diabetic CKD: obesity, diabetes, cardiovascular disease, renal function deterioration. evaluate treatments such as administration iSGLT2, VitE antioxidant therapy, or Mg supplementation. Plasma proteomics was performed Nx‐Zucker rats, found change families proteins similar those Unfortunately, were performed. would a good strategy gather different research groups aims develop common strategies share only results but also samples obtained patients animals optimize efforts.

Language: Английский

Citations

0
Blood to Biomarker Quantitation in Under One Hour with Rapid Proteomics using a Hyperthermoacidic Protease DOI Open Access

Steven M. Yannone,

Vikas Tuteja,

Olena Goleva

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 2, 2024

Abstract Multi-step multi-hour tryptic proteolysis has limited the utility of bottom-up proteomics for cases that require immediate quantitative information. The recently available hyperthermoacidic (HTA) protease “Krakatoa” digests samples in a single 5 to 30-minute step at pH 3 and >80 °C; conditions disrupt most cells tissues, denature proteins, block disulfide reformation. combination quick single-step sample preparation with high throughput dual trapping column analytical (DTSC) liquid chromatography-mass spectrometry (LC-MS) achieves “Rapid Proteomics” which time from collection actionable data is less than 1 hour. presented development systematic evaluation this methodology found reproducible quantitation over 160 proteins just microliter whole blood. Furthermore, preference HTA-protease intact peptides allows sensitive targeted Angiotensin I II bioactive under half an With these methods we analyzed serum plasma 53 individuals quantified were not detected trypsin. This assessment Rapid Proteomics suggests concentration circulating protein peptide biomarkers could be measured almost real-time by LC-MS. TOC Figure enables near monitoring blood biomarkers. One collected every 8 minutes, digested 20 then mass minutes. results delay datapoints

Language: Английский

Citations

0
An integrated proteomic and phosphoproteomic landscape of chronic kidney disease DOI Creative Commons
Linxiao Sun, Cheng Wang, Zhongjing Zhou

et al.

Journal of Proteomics, Journal Year: 2024, Volume and Issue: 311, P. 105355 - 105355

Published: Nov. 14, 2024

The prevalence of chronic kidney disease (CKD) is gradually rising worldwide. Patients often remain asymptomatic for an extended period, leaving them unaware their condition, which can lead to progressing end-stage renal and cause significant economic burden. Improved understanding CKD pathogenesis enhance early detection facilitate advances in drug development. Here, we performed proteomic phosphoproteomic analyses the mouse unilateral ureteral obstruction model explore molecular mechanisms injury. 474 significantly differentially expressed proteins 96 phosphoproteins were screened, respectively. Chronic injury involves complex metabolic pathways such as citrate cycle hematopoietic system proteome, mitochondrial oxidative phosphorylation suppression a notable alteration. analysis revealed upregulation epithelial mesenchymal transition P53 pathways, with corresponding increase Jun at serine 73. Utilizing HK2 cells, observed that reduction was consistently associated augmentation stress, subsequently activated induced apoptosis. Proteins act hubs these may be candidate targets intervention. These findings contribute current provide valuable insights future studies. SIGNIFICANCE: incidence annually varied etiologies, irreversibly fibrotic, treatment options are limited ineffective due deficient fibrosis mechanisms. Despite extensive efforts numerous omics studies conducted on fibrosis, date, no study has been undertaken investigate role phosphorylated UUO models. Previously, comprehensive transcriptome proteome based model, but potential alterations phosphoproteome not addressed. integrated landscape completed, first profiles model. Phosphoproteomic profile suggests models injury, core protein played key CKD. And preliminary correlation between P-Jun found base cells. Our work contributes deeper characteristics Identifying from diagnosis

Language: Английский

Citations

0