Pkcδ Activation is Involved in ROS-Mediated Mitochondrial Dysfunction and Apoptosis in Cardiomyocytes Exposed to Advanced Glycation End Products (Ages)

Yang, Yanyan; Tsai, Cheng Yen; Chen, Chien‐Lin; Kuo, Chia Hua; Hou, Chien-Wen; Cheng, Shi; Aneja, Ritu; Huang, Chih‐Yang; Kuo, Wei Wen

doi:10.14336/ad.2017.0924

Cited by 47 publications

(42 citation statements)

References 61 publications

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“…Briefly, AGE was prepared by incubating bovine serum albumin (A8806, BSA, fraction V, fatty acid-free, endotoxin-free; Sigma Chemical, 100 mg/mL) with D-glucose (1 M) in Dulbecco's phosphate-buffered saline (DPBS, 21600-010; Gibco) for 12 weeks at 37 • C. Unmodified BSA was prepared under the same conditions without glucose as a control. The fluorescence of the supernatant was determined (excitation 370 nm, emission 440 nm) using LJL Biosystems (Analyst TM AD, Sunnyvale, CA, USA), which confirmed the higher intensity of AGEs in AGE-modified BSA than in unmodified BSA in our previous paper [21]. The AGE solution was filter sterilized by a 0.8 µM Millex GP filter unit (Millipore, Billerica, MA, USA).…”

Section: Glucose-derived Age Preparationsupporting

confidence: 73%

“…By exploring the effects of DATS on survival markers, we found that DATS treatment increased p-Akt protein levels, indicating that DATS may maintain cardiomyoblast growth and apoptosis inhibition ( Figure 2B). Our prior studies demonstrated that PKCδ activation was involved in ROS-mediated mitochondrial dysfunction and apoptosis in response to AGE exposure [21]. To explore whether DATS could inhibit PKCδ-dependent apoptosis in AGE-exposed H9c2 cells, we performed Western blotting to examine the related proteins.…”

Section: Inhibitory Effect Of Dats On Age-induced Cardiac Apoptosis Amentioning

confidence: 99%

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Diallyl Trisulfide (DATS) Suppresses AGE-Induced Cardiomyocyte Apoptosis by Targeting ROS-Mediated PKCδ Activation

Hsieh

Zeng

et al. 2020

IJMS

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Chronic high-glucose exposure results in the production of advanced glycation end-products (AGEs) leading to reactive oxygen species (ROS) generation, which contributes to the development of diabetic cardiomyopathy. PKCδ activation leading to ROS production and mitochondrial dysfunction involved in AGE-induced cardiomyocyte apoptosis was reported in our previous study. Diallyl trisulfide (DATS) is a natural cytoprotective compound under various stress conditions. In this study, the cardioprotective effect of DATS against rat streptozotocin (STZ)-induced diabetic mellitus (DM) and AGE-induced H9c2 cardiomyoblast cell/neonatal rat ventricular myocyte (NRVM) damage was assessed. We observed that DATS treatment led to a dose-dependent increase in cell viability and decreased levels of ROS, inhibition of PKCδ activation, and recuded apoptosis-related proteins. Most importantly, DATS reduced PKCδ mitochondrial translocation induced by AGE. However, apoptosis was not inhibited by DATS in cells transfected with PKCδ-wild type (WT). Inhibition of PKCδ by PKCδ-kinase-deficient (KD) or rottlerin not only inhibited cardiac PKCδ activation but also attenuated cardiac cell apoptosis. Interestingly, overexpression of PKCδ-WT plasmids reversed the inhibitory effects of DATS on PKCδ activation and apoptosis in cardiac cells exposed to AGE, indicating that DATS may inhibit AGE-induced apoptosis by downregulating PKCδ activation. Similar results were observed in AGE-induced NRVM cells and STZ-treated DM rats following DATS administration. Taken together, our results suggested that DATS reduced AGE-induced cardiomyocyte apoptosis by eliminating ROS and downstream PKCδ signaling, suggesting that DATS has potential in diabetic cardiomyopathy (DCM) treatment.

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Section: Glucose-derived Age Preparationsupporting

confidence: 73%

Section: Inhibitory Effect Of Dats On Age-induced Cardiac Apoptosis Amentioning

confidence: 99%

Diallyl Trisulfide (DATS) Suppresses AGE-Induced Cardiomyocyte Apoptosis by Targeting ROS-Mediated PKCδ Activation

Hsieh

Zeng

et al. 2020

IJMS

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“…All of this agent can cuss increase the reactive oxygen spice (ROS) in cardiomyocytes. An increase in ROS at the cellular level is the start point in beginning apoptosis [33]. In this study although the oxidative stress marker was not measured, however apoptosis marker (caspase 3 and pro-caspase 3) measured and increased with DFO for four weeks.…”

Section: Discussionmentioning

confidence: 62%

Aerobic exercise and octopamine protects against deep-frying oil-induced cardiomyocyte apoptosis through modulation of caspase and pro-caspase 3

kianmehr

Azarbayjani

Peeri

et al. 2020

Preprint

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Background : Deep-frying is a common cooking method in which cooking is accompanied by carcinogenic byproducts such as acrolein. Acrolein is a toxic byproduct of lipid peroxidation, which has been implicated in pulmonary, cardiac, and neurodegenerative diseases. This study aimed to explore the effect of aerobic exercise and octopamine on caspase 3 and pro-caspase 3 expression levels in the heart tissue of rat exposed deep-frying oil. Methods : 30 male Wistar rats were divided into 5 groups (n=6 in each) including 1) control (CO), 2) deep-frying oil (DFO), 3) deep-frying oil+exercise (DFO+EXE), 4) deep-frying oil+octopamine (DFO+OCT), and 5) deep-frying oil+exercise+octopamine (DFO+EXE+OCT). The apoptotic effects of DFO in heart tissue were examined by TUNEL assay. Masson's trichrome stain used to study cardiomyocytes’ fibers. Moreover, caspase 3 and pro-caspase 3 genes and proteins expression in all groups were evaluated using quantitative real-time PCR and western blotting method, respectively. Results : Data showed a significant increase in apoptotic cells in the DFO-treated group ( P <0.05). Masson's trichrome stain analysis demonstrated that the number of cardiomyocytes' fibers are decreased, and collagen deposition is increased in the DFO group. In comparison, the collagen percentage was significantly reduced in exercise, OCT, and exercise+OCT groups. Also, the expression level of caspase 3 and pro-caspase 3 was significantly decreased in deep-frying oil+exercise+OCT group ( P <0.05). Conclusions : The results of our study show that DFO lead to programmed cell death via the activation of caspase in heart tissue. However, it seems that aerobic exercise with octopamine supplementation improves heart tissue by significantly decrease the expression of caspase 3 and pro-caspase 3 that inhibit apoptosis.

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“…Increased mitochondrial fission and/or attenuated fusion lead to mitochondrial fragmentation and disrupt cellular physiological function (Caja et al, 2017). Previous studies indicate that the increased mitochondrial fission leads to mitochondrial ROS (mtROS) generation and elevated apoptosis in endothelial cells (ECs) of diabetic patients (Shenouda et al, 2011;Yang et al, 2018;Galloway et al, 2012). Mitochondrial fragmentation, increased expression of the fission factor and reduced fusion protein levels were demonstrated in ECs of type 1 diabetic mice (Makino et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

eIF5a reduction via decreased Klf5 leads to cell senescence by mitochondrial fission in VSMCs

Zheng

et al. 2019

Preprint

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Though dysregulation of mitochondrial dynamics has been linked to cellular senescence, which contributes to advanced age-related disorders, it is unclear how Klf5, an essential transcriptional factor of cardiovascular remodeling, mediates the link between mitochondrial dynamics and vascular smooth muscle cell (VSMC) senescence. Here we show that Klf5 downregulation in VSMCs is correlated with rupture of abdominal aortic aneurysm (AAA), an age-related vascular disease. Mice lacking Klf5 in VSMCs exacerbate vascular senescence and progression of Ang II-induced AAA by facilitating ROS formation. Klf5 knockdown enhances, while Klf5 overexpression suppresses mitochondrial fission. Mechanistically, Klf5 activates eIF5a transcription through binding to the promoter of eIF5a, which in turn preserves mitochondrial integrity by interacting with Mfn1. Accordingly, decreased expression of eIF5a elicited by Klf5 downregulation leads to mitochondrial fission and excessive ROS production. Inhibition of mitochondrial fission decreases ROS production and VSMC senescence. Our studies provide a potential therapeutic target for age-related vascular disorders.

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Pkcδ Activation is Involved in ROS-Mediated Mitochondrial Dysfunction and Apoptosis in Cardiomyocytes Exposed to Advanced Glycation End Products (Ages)

Cited by 47 publications

References 61 publications

Diallyl Trisulfide (DATS) Suppresses AGE-Induced Cardiomyocyte Apoptosis by Targeting ROS-Mediated PKCδ Activation

Diallyl Trisulfide (DATS) Suppresses AGE-Induced Cardiomyocyte Apoptosis by Targeting ROS-Mediated PKCδ Activation

Aerobic exercise and octopamine protects against deep-frying oil-induced cardiomyocyte apoptosis through modulation of caspase and pro-caspase 3

eIF5a reduction via decreased Klf5 leads to cell senescence by mitochondrial fission in VSMCs

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