Bacterial Dna and Rna Induce Rat Cardiac Myocyte Contraction Depression in Vitro

Paladugu, Bhanu; Kumar, Anand; Parrillo, Joseph E.; Der, Sandy D.; Osman, Jailan; Mensing, Joel; Falvo, Lisa; Xu, Xiulong; Kumar, Aseem

doi:10.1097/00024382-200404000-00012

Cited by 23 publications

(13 citation statements)

References 37 publications

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“…First, to confirm the role of TLR9 to reduce contractility, we compared ex vivo crystalloid-perfused, beating hearts from wild-type and TLR9 −/− mice using the Langendorff method, which enabled us to eliminate the effect from circulating immune cells. Consistent with the earlier report using isolated cardiomyocytes in vitro (8), CpG oligodeoxynucleotides (CpG-ODN; a synthetic TLR9 ligand) significantly decreased cardiac contractility through TLR9 as early as 20 min following its administration without changing coronary flow (Fig. S1A).…”

Section: Tlr9 Reduces Energy Substrates In Cardiomyocytes With Activasupporting

confidence: 91%

“…It would be catastrophic for such organs with poor regenerative capacity, if TLR9 in nonimmune cells operated the same inflammatory signaling. Interestingly, bacterial DNA has recently been shown to decrease contractility in isolated cardiomyocytes within 30 min after administration (8). Although the precise mechanism and biological relevance of this phenomenon remains unknown, we speculated that TLR9 has a different role in cardiomyocytes.…”

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confidence: 93%

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TLR9 mediates cellular protection by modulating energy metabolism in cardiomyocytes and neurons

Shintani

Kapoor

Kaneko

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Toll-like receptors (TLRs) are the central players in innate immunity. In particular, TLR9 initiates inflammatory response by recognizing DNA, imported by infection or released from tissue damage. Inflammation is, however, harmful to terminally differentiated organs, such as the heart and brain, with poor regenerative capacity, yet the role of TLR9 in such nonimmune cells, including cardiomyocytes and neurons, is undefined. Here we uncover an unexpected role of TLR9 in energy metabolism and cellular protection in cardiomyocytes and neurons. TLR9 stimulation reduced energy substrates and increased the AMP/ATP ratio, subsequently activating AMPactivated kinase (AMPK), leading to increased stress tolerance against hypoxia in cardiomyocytes without inducing the canonical inflammatory response. Analysis of the expression profiles between cardiomyocytes and macrophages identified that unc93 homolog B1 (C. elegans) was a pivotal switch for the distinct TLR9 responses by regulating subcellular localization of TLR9. Furthermore, this alternative TLR9 signaling was also found to operate in differentiated neuronal cells. These data propose an intriguing model that the same ligand-receptor can concomitantly increase the stress tolerance in cardiomyocytes and neurons, whereas immune cells induce inflammation upon tissue injury.

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Section: Tlr9 Reduces Energy Substrates In Cardiomyocytes With Activasupporting

confidence: 91%

mentioning

confidence: 93%

TLR9 mediates cellular protection by modulating energy metabolism in cardiomyocytes and neurons

Shintani

Kapoor

Kaneko

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…5 The effect of rDNA fragments is similar to that of the E. coli DNA, which is realized through the TLR9 and results in the depression of the contractile function of cardiomyocytes, as shown previously. 14 In the presence of the inhibitor of these receptors, rDNA works nonspecifically-increasing the frequency of cardiomyocyte contractions. The accumulation of the CpG-rich sequences in cfDNA, analogous to rDNA, might have an influence on the myocardial cell operation.…”

Section: Discussionmentioning

confidence: 99%

Effect of Cell‐Free DNA of Patients with Cardiomyopathy and rDNA on the Frequency of Contraction of Electrically Paced Neonatal Rat Ventricular Myocytes in Culture

Bulicheva

Fidelina

Mkrtumova

et al. 2008

Annals of the New York Academy of Sciences

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There is evidence that infarcted myocardium contributes to the increase of cell-free DNA levels (cfDNA). We studied the effect of different human DNA fragments on the rate of contraction of the electrically paced neonatal rat ventricular myocytes in culture (spontaneously hypertensive line SHR). AT-rich fragments of the human satellite 3 tandem repeat (1q12 region) at a concentration of 1 ng/mL increase the frequency of cardiomyocyte contractions by 2-2.5 times. GC-rich fragments of the rDNA at 0.5 ng/mL decrease the cardiomyocyte contraction frequency by 1.5-2 times. The serum cfDNA of patients with acute myocardial infarction decreases the frequency of the contraction of cardiomyocytes proportionally to the amount of the rDNA fragments it contains. The rDNA effect is similar to the E. coli DNA effect and is presumably being realized through TLR9. In the presence of the inhibitor of these receptors, rDNA operates the same way as the fragment of the satellite 3-increasing the frequency of the cardiomyocyte contractions. Accumulation of the GC-rich fragments of the cfDNA in the blood of the AMI patients might have an influence on the contractile function of myocardial cells.

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“…Bacterial DNA and RNA derived from S. aureus and E. coli induce a concentration-dependent depression of rat cardiomyocyte function (75). Pretreatment with DNase or RNase abrogates this effect.…”

Section: Tlr9mentioning

confidence: 99%

Inflammation and Heart Diseases: Role of Toll-Like Receptor Signaling

Chao¹

2014

J Anesth Perioper Med

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Aim of review:Heart diseases such as septic cardiomyopathy, ischemic myocardial injury and acute myocarditis pose significant perioperative risk to surgical patients and present challenges to anesthesiologists. Myocardial inflammation is a common theme of these diseases and plays an important role in their pathogeneses. Toll-like receptors (TLRs) are an important part of the innate immune system. The aim of this article is to provide a brief review on the major landmark studies of TLRs and their signaling, the complex and critical role of TLRs in severe sepsis, ischemic myocardial injury, and myocarditis. The article intends to cover animal studies defining the molecular mechanisms by which TLR signaling contributes to the pathogenesis of these heart diseases as well as the recent clinical trials targeting TLR for sepsis intervention. Summary: Studies of the past decade have firmly established the role of TLR signaling in cardiac inflammation and dysfunction during severe sepsis, ischemic myocardial injury, and acute myocarditis. Understanding the complex cellular and molecular pathways by which TLR signaling controls myocardial inflammation and injury provides insight into the mechanisms of these cardiac diseases and will impact on how we diagnose and treat these critical conditions in the future.

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Bacterial Dna and Rna Induce Rat Cardiac Myocyte Contraction Depression in Vitro

Cited by 23 publications

References 37 publications

TLR9 mediates cellular protection by modulating energy metabolism in cardiomyocytes and neurons

TLR9 mediates cellular protection by modulating energy metabolism in cardiomyocytes and neurons

Effect of Cell‐Free DNA of Patients with Cardiomyopathy and rDNA on the Frequency of Contraction of Electrically Paced Neonatal Rat Ventricular Myocytes in Culture

Inflammation and Heart Diseases: Role of Toll-Like Receptor Signaling

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