Differential proteomic profiling identifies novel molecular targets of pterostilbene against experimental diabetes

Sireesh, Dornadula; Thiruppathi, Suresh; Rajaguru, P.; Umapathy, Dhamodharan; Suzuki, Takayoshi; Mohanram, Ramkumar K.

doi:10.1002/jcp.26835

Cited by 13 publications

(6 citation statements)

References 42 publications

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“…Our earlier studies confirmed that pterostilbene, an Nrf2 activator, conferred protection against oxidative stress by elevating the levels of Nrf2 and its downstream genes and against cytokine stress [22,24]. Further, the proteomic profiling of pancreatic tissue isolated from pterostilbene treated mice demonstrated that the majority of differentially regulated proteins were associated with oxidative and ER stress pathways [61].…”

Section: Discussionsupporting

confidence: 69%

Pharmacological activation of Nrf2 by rosolic acid attenuates endoplasmic reticulum stress in endothelial cells

Amin

Rajaguru

Sarkar

et al. 2020

Preprint

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Endoplasmic reticulum (ER) plays a key role in the folding, modification, and trafficking of proteins. When the homeostasis of the ER is disturbed, un/misfolded proteins accumulate in the ER which leads to ER stress. Sustained ER stress results in apoptosis, which is associated with various diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major transcription factor in redox homeostasis by regulating various genes associated with detoxification and cell-protective mechanisms. We found that Rosolic acid (RA) treatment dose-dependently activates Nrf2 in endothelial cells using the enzyme fragment complementation assay. The cytoprotective role of RA against ER stress-induced endothelial apoptosis and its molecular mechanism was explored in the present study. The Nrf2 and its target genes, as well as ER stress marker expressions, were measured by qPCR in ER stress-exposed endothelial cells. The contribution of Nrf2 in RA-mediated defense mechanism in endothelial cells was established by knockout studies using Nrf2-CRISPR/Cas9. The treatment with RA to ER stress-induced endothelial cells exhibited activation of Nrf2, as demonstrated by Nrf2 translocation and reduction of ER stress markers. We found that the Nrf2 knockout sensitized the endothelial cells against ER stress, and further, RA failed to mediate its cytoprotective effect. Proteomic studies using LC-MS/MS revealed that among the 1370 proteins detected, we found 296 differentially regulated proteins in ER stress-induced endothelial cells, and RA administration ameliorated 71 proteins towards the control levels. Of note, the ER stress in endothelial cells was attenuated by the treatment with the RA, suggesting the role of the Nrf2 activator in the pathological conditions of ER stress-associated diseases.

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Section: Discussionsupporting

confidence: 69%

Pharmacological activation of Nrf2 by rosolic acid attenuates endoplasmic reticulum stress in endothelial cells

Amin

Rajaguru

Sarkar

et al. 2020

Preprint

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“…Our findings indicated that the administration of PTS normalized the levels of 315 proteins that were modulated in diabetic mice. Outstandingly, a major proportion of these proteins were involved in the regulation of redox imbalance, the antioxidative stress response, the unfolded protein response, and ER degradation pathways, indicating that PTS treatment plays a crucial role in the rehabilitation of defective metabolic processes and stress sensors in diabetes [ 101 ].…”

Section: Therapeutic Properties Of Ptsmentioning

confidence: 99%

New Insights into Dietary Pterostilbene: Sources, Metabolism, and Health Promotion Effects

et al. 2022

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Pterostilbene (PTS), a compound most abundantly found in blueberries, is a natural analog of resveratrol. Several plant species, such as peanuts and grapes, produce PTS. While resveratrol has been extensively studied for its antioxidant properties, recent evidence also points out the diverse therapeutic potential of PTS. Several studies have identified the robust pharmacodynamic features of PTS, including better intestinal absorption and elevated hepatic stability than resveratrol. Indeed, due to its higher bioavailability paired with reduced toxicity compared to other stilbenes, PTS has become an attractive drug candidate for the treatment of several disease conditions, including diabetes, cancer, cardiovascular disease, neurodegenerative disorders, and aging. This review article provides an extensive summary of the nutraceutical potential of PTS in various disease conditions while discussing the crucial mechanistic pathways implicated. In particular, we share insights from our studies about the Nrf2-mediated effect of PTS in diabetes and associated complications. Moreover, we elucidate the important sources of PTS and discuss in detail its pharmacokinetics and the range of formulations and routes of administration used across experimental studies and human clinical trials. Furthermore, this review also summarizes the strategies successfully used to improve dietary availability and the bio-accessibility of PTS.

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“…An imbalance of insulin generation or dysfunction of insulinproducing pancreatic β-cells leads to type 1 diabetes (T1D), 135 which plays a key role in the progression of CD. 117 It has been reported that OS is implicated in the progression of diabetes.…”

Section: Diabetesmentioning

confidence: 99%

“…An imbalance of insulin generation or dysfunction of insulin-producing pancreatic β-cells leads to type 1 diabetes (T1D), which plays a key role in the progression of CD . It has been reported that OS is implicated in the progression of diabetes. , An excess of blood glucose can also lead to protein glycation and the oxidation of bound glucose and thus, to the generation of AGEs, which are directly correlated with type 2 diabetes .…”

Section: Oxidative-stress-related Diseasesmentioning

confidence: 99%

Section: Oxidative-stress-related Diseasesmentioning

confidence: 99%

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Redox Proteomes in Human Physiology and Disease Mechanisms

Mannaa

Hanisch

2019

J. Proteome Res.

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Redox proteomics is a field of proteomics that is concerned with the characterization of the oxidation state of proteins to gain information about their modulated structure, function, activity, and involvement in different physiological pathways. Oxidative modifications of proteins have been shown to be implicated in normal physiological processes of cells as well as in pathomechanisms leading to the development of cancer, diabetes, neurodegenerative diseases, and some rare hereditary metabolic diseases, like classic galactosemia. Reactive oxygen species generate a variety of reversible and irreversible modifications in amino acid residue side chains and within the protein backbone. These oxidative post-translational modifications (Ox-PTMs) can participate in the activation of signal transduction pathways and mediate the toxicity of harmful oxidants. Thus the application of advanced redox proteomics technologies is important for gaining insights into molecular mechanisms of diseases. Mass-spectrometry-based proteomics is one of the most powerful methods that can be used to give detailed qualitative and quantitative information on protein modifications and allows us to characterize redox proteomes associated with diseases. This Review illustrates the role and biological consequences of Ox-PTMs under basal and oxidative stress conditions by focusing on protein carbonylation and S-glutathionylation, two abundant modifications with an impact on cellular pathways that have been intensively studied during the past decade.

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Differential proteomic profiling identifies novel molecular targets of pterostilbene against experimental diabetes

Cited by 13 publications

References 42 publications

Pharmacological activation of Nrf2 by rosolic acid attenuates endoplasmic reticulum stress in endothelial cells

Pharmacological activation of Nrf2 by rosolic acid attenuates endoplasmic reticulum stress in endothelial cells

New Insights into Dietary Pterostilbene: Sources, Metabolism, and Health Promotion Effects

Redox Proteomes in Human Physiology and Disease Mechanisms

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