Hyperoxaluria-induced tubular ischemia: the effect of verapamil on the limitation of tissue HIF-1 alpha levels in renal parenchyma

Yencilek, Faruk; Sarıca, Kemal; Eryıldırım, Bilal; Erturhan, Sakıp; Karakök, Metin; Kuyumcuoğlu, Uğur

doi:10.1007/s11255-009-9615-0

Cited by 4 publications

(1 citation statement)

References 26 publications

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“…For example, carmustine enhances chemotherapeutic efficacy by attenuating AKT activity in gliomas [ 42 ]. As a protective agent, verapamil [ 43 ] was found to significantly reduce the expression of HIF-1 alpha in many cells [ 44 ]. Liu and coworkers work also provided evidence for a crucial role for the over expression of MEK/ERK pathway in protecting kidney SP cells from ischemic/hypoxic injury, and Verapamil treatment reversed MEK-induced cell viability [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

A linear programming computational framework integrates phosphor-proteomics and prior knowledge to predict drug efficacy

Wang

Yan

et al. 2017

BMC Syst Biol

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BackgroundIn recent years, the integration of ‘omics’ technologies, high performance computation, and mathematical modeling of biological processes marks that the systems biology has started to fundamentally impact the way of approaching drug discovery. The LINCS public data warehouse provides detailed information about cell responses with various genetic and environmental stressors. It can be greatly helpful in developing new drugs and therapeutics, as well as improving the situations of lacking effective drugs, drug resistance and relapse in cancer therapies, etc.ResultsIn this study, we developed a Ternary status based Integer Linear Programming (TILP) method to infer cell-specific signaling pathway network and predict compounds’ treatment efficacy. The novelty of our study is that phosphor-proteomic data and prior knowledge are combined for modeling and optimizing the signaling network. To test the power of our approach, a generic pathway network was constructed for a human breast cancer cell line MCF7; and the TILP model was used to infer MCF7-specific pathways with a set of phosphor-proteomic data collected from ten representative small molecule chemical compounds (most of them were studied in breast cancer treatment). Cross-validation indicated that the MCF7-specific pathway network inferred by TILP were reliable predicting a compound’s efficacy. Finally, we applied TILP to re-optimize the inferred cell-specific pathways and predict the outcomes of five small compounds (carmustine, doxorubicin, GW-8510, daunorubicin, and verapamil), which were rarely used in clinic for breast cancer. In the simulation, the proposed approach facilitates us to identify a compound’s treatment efficacy qualitatively and quantitatively, and the cross validation analysis indicated good accuracy in predicting effects of five compounds.ConclusionsIn summary, the TILP model is useful for discovering new drugs for clinic use, and also elucidating the potential mechanisms of a compound to targets.Electronic supplementary materialThe online version of this article (10.1186/s12918-017-0501-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

A linear programming computational framework integrates phosphor-proteomics and prior knowledge to predict drug efficacy

Wang

Yan

et al. 2017

BMC Syst Biol

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Hyperoxaluria-induced tubular ischemia: the effects of verapamil on the antioxidant capacity of the affected kidneys

et al. 2016

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To evaluate the potential protective effects of a calcium channel blocker (Verapamil) on the oxidative stress related changes with an emphasis on the antioxidant capacity of the kidneys an experimental study in rats was performed. A total of 44 rats have been included. Hyperoxaluria was induced in Group 1 by continuous administration of ethylene glycol (EG). Animals in Group 2 received Verapamil in addition to EG. Animals in Group 3 constituted the control group. In addition to the evaluation of tissue and serum levels of three scavenging enzymes, NO, MDA and T-AOC; the presence and degree of crystal formation in renal parenchyma were evaluated in all animals after 7 and 28 days. Our data demonstrated that in addition to the lower level of all three scavenging enzymes (SOD, CAT and GSH) particularly during late phase evaluation (4 weeks); the total antioxidant capacity (T-AOC) of these kidneys were also higher when compared with the animals receiving EG only. Tissue and serum levels of both NO and MDA indicated the preventive effect of Verapamil on the oxidative stress induced changes. Very limited or no crystallization in the kidneys treated with verapamil during early and late phase examination was observed when compared with considerable crystal formation in Group 2 animals. Verapamil treatment may preserve the oxidant capacity of the kidneys and subsequently limit the crystal deposition induced by hyperoxaluria. Verapamil could therefore be considered in the management of kidney stone formation particularly in cases with recurrent kidney stone disease.

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Predicting drug efficacy using a linear programming computational framework

Ji,

Wang,

Yan

et al. 2024

Computational Intelligence in Protein-Ligand Interaction Analysis

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Hyperoxaluria-induced tubular ischemia: the effect of verapamil on the limitation of tissue HIF-1 alpha levels in renal parenchyma

Cited by 4 publications

References 26 publications

A linear programming computational framework integrates phosphor-proteomics and prior knowledge to predict drug efficacy

A linear programming computational framework integrates phosphor-proteomics and prior knowledge to predict drug efficacy

Hyperoxaluria-induced tubular ischemia: the effects of verapamil on the antioxidant capacity of the affected kidneys

Predicting drug efficacy using a linear programming computational framework

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