Mitochondria in the pathogenesis of diabetes: a proteomic view

Chen, Xiu-Lan; Wei, Shasha; Yang, Fuquan

doi:10.1007/s13238-012-2043-4

Cited by 27 publications

(25 citation statements)

References 104 publications

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“…Cumulative evidence has linked altered energy metabolism and mitochondrial modification to the pathogenesis of diabetes and its complications (74). In this sense, proteomic efforts in different tissues from mouse models of type 1 diabetes (T1DM) detected increased expression of several mitochondrial proteins related to FAO, TCA cycle and oxidative stress (75,76).…”

Section: Figmentioning

confidence: 99%

Stable Isotope Labeling with Amino Acids (SILAC)-Based Proteomics of Primary Human Kidney Cells Reveals a Novel Link between Male Sex Hormones and Impaired Energy Metabolism in Diabetic Kidney Disease

Clotet

Soler

Riera

et al. 2017

Molecular & Cellular Proteomics

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Male sex predisposes to many kidney diseases. Considering that androgens exert deleterious effects in a variety of cell types within the kidney, we hypothesized that dihydrotestosterone (DHT) would alter the biology of the renal tubular cell by inducing changes in the proteome. We employed stable isotope labeling with amino acids (SILAC) in an indirect spike-in fashion to accurately quantify the proteome in DHT-and 17␤-estradiol (EST)-treated human proximal tubular epithelial cells (PTEC). Of the 5043 quantified proteins, 76 were differentially regulated. Biological processes related to energy metabolism were significantly enriched among DHT-regulated proteins. SILAC ratios of 3 candidates representing glycolysis, Nacetylglucosamine metabolism and fatty acid ␤-oxidation, namely glucose-6-phosphate isomerase (GPI), glucosamine-6-phosphate-N-acetyltransferase 1 (GNPNAT1), and mitochondrial trifunctional protein subunit alpha (HADHA), were verified in vitro. In vivo, renal GPI and HADHA protein expression was significantly increased in males. Furthermore, male sex was associated with significantly higher GPI, GNPNAT1, and HADHA kidney protein expression in two different murine models of diabetes. Enrichment analysis revealed a link between our DHTregulated proteins and oxidative stress within the diabetic kidney. This finding was validated in vivo, as we observed increased oxidative stress levels in control and diabetic male kidneys, compared with females. This in depth quantitative proteomics study of human primary PTEC response to sex hormone administration suggests that male sex hormone stimulation results in perturbed energy metabolism in kidney cells, and that this perturbation results in increased oxidative stress in the renal cortex. Chronic Kidney Disease (CKD)1 often results in irreversible deterioration of renal function that can progress to renal failure (1). Sex plays a relevant role in the progression and severity of many kidney diseases (2). At a clinical level, it is From the ‡Department

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Section: Figmentioning

confidence: 99%

Stable Isotope Labeling with Amino Acids (SILAC)-Based Proteomics of Primary Human Kidney Cells Reveals a Novel Link between Male Sex Hormones and Impaired Energy Metabolism in Diabetic Kidney Disease

Clotet

Soler

Riera

et al. 2017

Molecular & Cellular Proteomics

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“…Along with physiological signal mediators, ECVs appear as potential new tools for clinical diagnostics and may be useful in novel treatment modalities (Lima et al, 2009; Chen et al, 2012). Several groups are currently looking at ECVs as potential carriers of therapeutic drugs or molecules that would down-regulate toxic proteins or elicit an anti-tumor immune response when encapsulating specific siRNAs or adeno-associated viral vectors (Alvarez-Erviti et al, 2011; Maguire et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Alternative Methods for Characterization of Extracellular Vesicles

Momen-Heravi¹,

Balaj²,

Alian³

et al. 2012

Front. Physio.

122

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Extracellular vesicles (ECVs) are nano-sized vesicles released by all cells in vitro as well as in vivo. Their role has been implicated mainly in cell–cell communication, but also in disease biomarkers and more recently in gene delivery. They represent a snapshot of the cell status at the moment of release and carry bioreactive macromolecules such as nucleic acids, proteins, and lipids. A major limitation in this emerging new field is the availability/awareness of techniques to isolate and properly characterize ECVs. The lack of gold standards makes comparing different studies very difficult and may potentially hinder some ECVs-specific evidence. Characterization of ECVs has also recently seen many advances with the use of Nanoparticle Tracking Analysis, flow cytometry, cryo-electron microscopy instruments, and proteomic technologies. In this review, we discuss the latest developments in translational technologies involving characterization methods including the facts in their support and the challenges they face.

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“…SM uptakes more than 80% of human body glucose in an insulin‐sensitive manner, thus playing a major role in the development of peripheral and whole body IR . Impaired insulin‐dependent glucose uptake in SM contributes significantly to the pathogenesis of T2D and the metabolic syndrome . Muscle IR has been associated with increased intramyocellular lipid content, contractile weakness, reduced mitochondrial mass, and a decline in crucial ATP‐dependent cellular processes .…”

Section: Mitochondrial Proteomics Targeting Metabolic Tissuesmentioning

confidence: 99%

Mitochondria in metabolic disease: Getting clues from proteomic studies

et al. 2014

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Mitochondria play a key role as major regulators of cellular energy homeostasis, but in the context of mitochondrial dysfunction, mitochondria may generate reactive oxidative species and induce cellular apoptosis. Indeed, altered mitochondrial status has been linked to the pathogenesis of several metabolic disorders and specially disorders related to insulin resistance, such as obesity, type 2 diabetes, and other comorbidities comprising the metabolic syndrome. In the present review, we summarize information from various mitochondrial proteomic studies of insulin-sensitive tissues under different metabolic states. To that end, we first focus our attention on the pancreas, as mitochondrial malfunction has been shown to contribute to beta cell failure and impaired insulin release. Furthermore, proteomic studies of mitochondria obtained from liver, muscle, and adipose tissue are summarized, as these tissues constitute the primary insulin target metabolic tissues. Since recent advances in proteomic techniques have exposed the importance of PTMs in the development of metabolic disease, we also present information on specific PTMs that may directly affect mitochondria during the pathogenesis of metabolic disease. Specifically, mitochondrial protein acetylation, phosphorylation, and other PTMs related to oxidative damage, such as nitrosylation and carbonylation, are discussed.

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Mitochondria in the pathogenesis of diabetes: a proteomic view

Cited by 27 publications

References 104 publications

Stable Isotope Labeling with Amino Acids (SILAC)-Based Proteomics of Primary Human Kidney Cells Reveals a Novel Link between Male Sex Hormones and Impaired Energy Metabolism in Diabetic Kidney Disease

Stable Isotope Labeling with Amino Acids (SILAC)-Based Proteomics of Primary Human Kidney Cells Reveals a Novel Link between Male Sex Hormones and Impaired Energy Metabolism in Diabetic Kidney Disease

Alternative Methods for Characterization of Extracellular Vesicles

Mitochondria in metabolic disease: Getting clues from proteomic studies

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