Activation of Toll-Like Receptors and Inflammasome Complexes in the Diabetic Cardiomyopathy-Associated Inflammation

Fuentes-Antrás, Jesús; Ioan, A; Tuñón, José; Egido, Jesús; Lorenzo, Óscar

doi:10.1155/2014/847827

Cited by 80 publications

(60 citation statements)

References 120 publications

(155 reference statements)

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“…Under normal physiological conditions, NF-κB forms a complex with its inhibitors, the IκBs (α or β), and is maintained in the cytosol in this inactive state. When IκBs are phosphorylated by IKKα or IKKβ, NF-κB is released and transfers to the nucleus, subsequently activating a large range of genes implicating proinflammatory cytokines [4,31,32]. This action may contribute to explain the decreased nucleic levels of NF-κB by KPF treatment in our study (Fig.…”

Section: Discussionmentioning

confidence: 59%

Kaempferol alleviates insulin resistance via hepatic IKK/NF-κB signal in type 2 diabetic rats

Luo

Yang

Tang

et al. 2015

International Immunopharmacology

144

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Section: Discussionmentioning

confidence: 59%

Kaempferol alleviates insulin resistance via hepatic IKK/NF-κB signal in type 2 diabetic rats

Luo

Yang

Tang

et al. 2015

International Immunopharmacology

144

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“…A recent study also shows that the ROS-activated MAPK pathway attributes to the HG-induced cardiac cell injury [33]. However, the intracellular mechanisms responsible for the hyperglycemia-induced cardiac injury and inflammation are complicated, several signal molecules, including TLR4 [22, 23] and RIP3 [21, 25] have been shown to participate in the cardiac injury caused by hyperglycemia. But what is the relationship between ROS, TLR4 and RIP3 is still unclear in the HG-treated cardiac cells.…”

Section: Discussionmentioning

confidence: 99%

“…To date, multiple factors, such as ROS [7, 19-21], chronic inflammation [20, 22], cell death (including apoptosis and necroptosis) [7, 19-21], and activity of several signaling molecules, for example, toll-like receptors (TLRs) [22, 23], have been demonstrated to implicate in the hyperglycemia-induced cardiac injury. Importantly, the above factors can interact or crosstalk, consisting of the complicated intracellular signal mechanisms.…”

Section: Introductionmentioning

confidence: 99%

The Opening of ATP-Sensitive K+ Channels Protects H9c2 Cardiac Cells Against the High Glucose-Induced Injury and Inflammation by Inhibiting the ROS-TLR4-Necroptosis Pathway

Liang

Chen²,

Zheng

et al. 2017

Cell Physiol Biochem

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Background/Aims: Hyperglycemia activates multiple signaling molecules, including reactive oxygen species (ROS), toll-like receptor 4 (TLR4), receptor-interacting protein 3 (RIP3, a kinase promoting necroptosis), which mediate hyperglycemia-induced cardiac injury. This study explored whether inhibition of ROS-TLR4-necroptosis pathway contributed to the protection of ATP-sensitive K⁺ (K_ATP) channel opening against high glucose-induced cardiac injury and inflammation. Methods: H9c2 cardiac cells were treated with 35 mM glucose (HG) to establish a model of HG-induced insults. The expression of RIP3 and TLR4 were tested by western blot. Generation of ROS, cell viability, mitochondrial membrane potential (MMP) and secretion of inflammatory cytokines were measured as injury indexes. Results: HG increased the expression of TLR4 and RIP3. Necrostatin-1 (Nec-1, an inhibitor of necroptosis) or TAK-242 (an inhibitor of TLR4) co-treatment attenuated HG-induced up-regulation of RIP3. Diazoxide (DZ, a mitochondrial K_ATP channel opener) or pinacidil (Pin, a non-selective K_ATP channel opener) or N-acetyl-L-cysteine (NAC, a ROS scavenger) pre-treatment blocked the up-regulation of TLR4 and RIP3. Furthermore, pre-treatment with DZ or Pin or NAC, or co-treatment with TAK-242 or Nec-1 attenuated HG-induced a decrease in cell viability, and increases in ROS generation, MMP loss and inflammatory cytokines secretion. However, 5-hydroxy decanoic acid (5-HD, a mitochondrial K_ATP channel blocker) or glibenclamide (Gli, a non-selective K_ATP channel blocker) pre-treatment did not aggravate HG-induced injury and inflammation. Conclusion: K_ATP channel opening protects H9c2 cells against HG-induced injury and inflammation by inhibiting ROS-TLR4-necroptosis pathway.

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“…[4][5][6] Inflammatory signaling in cardiomyocytes usually occurs as an early response to myocardial injury and entails overproduction of mitochondrial reactive oxygen species (ROS). 7 The innate immune system plays a crucial role in acute inflammation caused by microbial infection or tissue damage. 2 Pattern recognition receptors recognize not only pathogen-associated molecular patterns but also endogenous molecules released from damaged cells, termed damageassociated molecular patterns (DAMPs).…”

mentioning

confidence: 99%

Sterile Inflammation and Degradation Systems in Heart Failure

Nishida

Otsu

2017

Circ J

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In most patients with chronic heart failure (HF), levels of circulating cytokines are elevated and the elevated cytokine levels correlate with the severity of HF and prognosis. Various stresses induce subcellular component abnormalities, such as mitochondrial damage. Damaged mitochondria induce accumulation of reactive oxygen species and apoptogenic proteins, and subcellular inflammation. The vicious cycle of subcellular component abnormalities, inflammatory cell infiltration and neurohumoral activation induces cardiomyocyte injury and death, and cardiac fibrosis, resulting in cardiac dysfunction and HF. Quality control mechanisms at both the protein and organelle levels, such as elimination of apoptogenic proteins and damaged mitochondria, maintain cellular homeostasis. An imbalance between protein synthesis and degradation is likely to result in cellular dysfunction and disease. Three major protein degradation systems have been identified, namely the cysteine protease system, autophagy, and the ubiquitin proteasome system. Autophagy was initially believed to be a non-selective process. However, recent studies have described the process of selective mitochondrial autophagy, known as mitophagy. Elimination of damaged mitochondria by autophagy is important for maintenance of cellular homeostasis. DNA and RNA degradation systems also play a critical role in regulating inflammation and maintaining cellular homeostasis mediated by damaged DNA clearance and post-transcriptional regulation, respectively. This review discusses some recent advances in understanding the role of sterile inflammation and degradation systems in HF.

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Activation of Toll-Like Receptors and Inflammasome Complexes in the Diabetic Cardiomyopathy-Associated Inflammation

Cited by 80 publications

References 120 publications

Kaempferol alleviates insulin resistance via hepatic IKK/NF-κB signal in type 2 diabetic rats

Kaempferol alleviates insulin resistance via hepatic IKK/NF-κB signal in type 2 diabetic rats

The Opening of ATP-Sensitive K+ Channels Protects H9c2 Cardiac Cells Against the High Glucose-Induced Injury and Inflammation by Inhibiting the ROS-TLR4-Necroptosis Pathway

Sterile Inflammation and Degradation Systems in Heart Failure

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