Inhibition of protein kinase C βII isoform ameliorates methylglyoxal advanced glycation endproduct-induced cardiomyocyte contractile dysfunction

Zhang, Liwei; Huang, Dangsheng; Shen, Dong; Zhang, Chunhong; Ma, Yun; Babcock, Sara A.; Chen, Bingyang; Ren, Jun

doi:10.1016/j.lfs.2013.11.011

Cited by 14 publications

(10 citation statements)

References 37 publications

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“…Treatment with PKC inhibitor chelerythrine or BIM-1 abolished fibroblast growth factor-2 (FGF-2) mediated protection against DOX-induced apoptosis, suggesting that PKC activation is an important prosurvival mechanism downstream of FGF-2 [209]. Interestingly, treatment with Ly333531, a specific PKC β inhibitor, attenuated mitochondrial depolarization and apoptosis in response to alcohol and advanced glycation end product, indicating a proapoptotic role of PKC β [210, 211]. …”

Section: Pkcmentioning

confidence: 99%

Signaling Pathways in Cardiac Myocyte Apoptosis

Xia

Liu

Cheng

2016

BioMed Research International

130

131

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Cardiovascular diseases, the number 1 cause of death worldwide, are frequently associated with apoptotic death of cardiac myocytes. Since cardiomyocyte apoptosis is a highly regulated process, pharmacological intervention of apoptosis pathways may represent a promising therapeutic strategy for a number of cardiovascular diseases and disorders including myocardial infarction, ischemia/reperfusion injury, chemotherapy cardiotoxicity, and end-stage heart failure. Despite rapid growth of our knowledge in apoptosis signaling pathways, a clinically applicable treatment targeting this cellular process is currently unavailable. To help identify potential innovative directions for future research, it is necessary to have a full understanding of the apoptotic pathways currently known to be functional in cardiac myocytes. Here, we summarize recent progress in the regulation of cardiomyocyte apoptosis by multiple signaling molecules and pathways, with a focus on the involvement of these pathways in the pathogenesis of heart disease. In addition, we provide an update regarding bench to bedside translation of this knowledge and discuss unanswered questions that need further investigation.

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Section: Pkcmentioning

confidence: 99%

Signaling Pathways in Cardiac Myocyte Apoptosis

Xia

Liu

Cheng

2016

BioMed Research International

130

131

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“…Furthermore, age-related comorbidities confound the expression of various isoforms. PKC α and β are increased with diabetes leading to the enhanced formation of advanced glycosylated end products [60, 61]. PKC δ and β are increased with atherosclerosis and contribute to endothelial cell damage [62, 63].…”

Section: Pkc and Agingmentioning

confidence: 99%

Common Mechanisms of Alzheimer's Disease and Ischemic Stroke: The Role of Protein Kinase C in the Progression of Age-Related Neurodegeneration

Lucke‐Wold

Turner

Logsdon

et al. 2014

JAD

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Ischemic stroke and Alzheimer’s disease (AD), despite being distinct disease entities, share numerous pathophysiological mechanisms such as those mediated by inflammation, immune exhaustion, and neurovascular unit compromise. An important shared mechanistic link is acute and chronic changes in protein kinase C (PKC) activity. PKC isoforms have widespread functions important for memory, blood-brain barrier maintenance, and injury repair that change as the body ages. Disease states accelerate PKC functional modifications. Mutated forms of PKC can contribute to neurodegeneration and cognitive decline. In some cases the PKC isoforms are still functional but are not successfully translocated to appropriate locations within the cell. The deficits in proper PKC translocation worsen stroke outcome and amyloid-β toxicity. Cross talk between the innate immune system and PKC pathways contribute to the vascular status within the aging brain. Unfortunately, comorbidities such as diabetes, obesity, and hypertension disrupt normal communication between the two systems. The focus of this review is to highlight what is known about PKC function, how isoforms of PKC change with age, and what additional alterations are consequences of stroke and AD. The goal is to highlight future therapeutic targets that can be applied to both the treatment and prevention of neurologic disease. Although the pathology of ischemic stroke and AD are different, the similarity in PKC responses warrants further investigation, especially as PKC-dependent events may serve as an important connection linking age-related brain injury.

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“…Several studies in the past have indicated that the PKC path way is associated with oxidative stress induced by ROS synthesis (24–27,48,49). PKC regulates NADPH oxidase activity and induces ROS synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…Studies on cardiomyocytes, epithelial cells and retinal diabetic nephropathy have shown that the isoform of protein kinase C (PKC) and PKC β2 (PKCβ2) plays an important role in AGE-mediated cell damage and kidney damage. By increasing PKCβ2 expression, AGEs enhance PKCβ2 activity, as well as the effects and displacement of PKCβ2, increasing ROS formation, which ultimately causes oxidative damage (24–27). Our previous study demonstrated that TRB3 activated PKCδ and was involved in high-fat-mediated β-cell apoptosis (22).…”

Section: Introductionmentioning

confidence: 99%

TRB3 mediates advanced glycation end product-induced apoptosis of pancreatic β-cells through the protein kinase C β pathway

Wang

Zhang

et al. 2017

International Journal of Molecular Medicine

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Advanced glycation end products (AGEs), which accumulate in the body during the development of diabetes, may be one of the factors leading to pancreatic β-cell failure and reduced β-cell mass. However, the mechanisms responsible for AGE-induced apoptosis remain unclear. This study identified the role and mechanisms of action of tribbles homolog 3 (TRB3) in AGE-induced β-cell oxidative damage and apoptosis. Rat insulinoma cells (INS-1) were treated with 200 µg/ml AGEs for 48 h, and cell apoptosis was then detected by TUNEL staining and flow cytometry. The level of intracellular reactive oxygen species (ROS) was measured by a fluorescence assay. The expression levels of receptor of AGEs (RAGE), TRB3, protein kinase C β2 (PKCβ2) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) were evaluated by RT-qPCR and western blot analysis. siRNA was used to knockdown TRB3 expression through lipofection, followed by an analysis of the effects of TRB3 on PKCβ2 and NOX4. Furthermore, the PKCβ2-specific inhibitor, LY333531, was used to analyze the effects of PKCβ2 on ROS levels and apoptosis. We found that AGEs induced the apoptosis of INS-1 cells and upregulated RAGE and TRB3 expression. AGEs also increased ROS levels in β-cells. Following the knockdown of TRB3, the AGE-induced apoptosis and intracellular ROS levels were significantly decreased, suggesting that TRB3 mediated AGE-induced apoptosis. Further experiments demonstrated that the knockdown of TRB3 decreased the PKCβ2 and NOX4 expression levels. When TRB3 was knocked down, the cells expressed decreased levels of PKCβ2 and NOX4. The PKCβ2-specific inhibitor, LY333531, also reduced AGE-induced apoptosis and intracellular ROS levels. Taken together, our data suggest that TRB3 mediates AGE-induced oxidative injury in β-cells through the PKCβ2 pathway.

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Inhibition of protein kinase C βII isoform ameliorates methylglyoxal advanced glycation endproduct-induced cardiomyocyte contractile dysfunction

Cited by 14 publications

References 37 publications

Signaling Pathways in Cardiac Myocyte Apoptosis

Signaling Pathways in Cardiac Myocyte Apoptosis

Common Mechanisms of Alzheimer's Disease and Ischemic Stroke: The Role of Protein Kinase C in the Progression of Age-Related Neurodegeneration

TRB3 mediates advanced glycation end product-induced apoptosis of pancreatic β-cells through the protein kinase C β pathway

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