Lipopolysaccharide induces apoptosis in adult rat  ventricular myocytes via cardiac AT<sub>1</sub> receptors

Li, Hai Ling; Suzuki, Jun; Bayna, Evelyn; Zhang, Fu‐Min; Molle, Erminia Dalle; Clark, Aaron; Engler, Robert L.; Lew, Wilbur Y.W.

doi:10.1152/ajpheart.00701.2001

Cited by 62 publications

(56 citation statements)

References 43 publications

(56 reference statements)

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“…6 Seven days after MI, the heart was arrested in diastole, excised, and sliced into 3 sections perpendicular to the long axis. The slices were fixed in 3.7% formaldehyde solution for 24 hours, paraffin embedded, sectioned (5 m), and mounted on glass slides.…”

Section: Apoptosismentioning

confidence: 99%

Increased Cardiac Adenylyl Cyclase Expression Is Associated With Increased Survival After Myocardial Infarction

et al. 2006

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Section: Apoptosismentioning

confidence: 99%

Increased Cardiac Adenylyl Cyclase Expression Is Associated With Increased Survival After Myocardial Infarction

et al. 2006

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“…[32][33][34] Losartan inhibits the LPS-induced apoptosis of rat ventricular myocytes. 35) Ang II induces the production of IL-6 by rat vascular smooth muscle cells and that of TNF-a by rat renal tubules. 36,37) Taken together, it is likely that losartan inhibits the LPS-induced upregulation of cardiac expression of B 2 -receptor mRNA by antagonizing the AT 1 -receptor-mediated effect of Ang II on TNF-a production in myocardium.…”

Section: Discussionmentioning

confidence: 96%

The Lipopolysaccharide-Induced Up-Regulation of Bradykinin B2-Receptor in the Mouse Heart Is Mediated by Tumor Necrosis Factor-.ALPHA. and Angiotensin II

Yayama

Hiyoshi

Sugiyama

et al. 2006

Biological & Pharmaceutical Bulletin

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Lipopolysaccharide (LPS) is one of the most potent and widely studied signal molecules involved in the initiation of septic shock. LPS activates multiple cells to release cytokines (such as tumor necrosis factor (TNF)-a, interleukin (IL)-1b, IL-6, interferon-g), nitric oxide (NO), metabolites of arachidonic acid, platelet-activating factor, and kinins. 1,2) These mediators contribute to the subsequent cellular responses, including increased vascular permeability, the generation of toxic oxygen metabolites, the generation of microthrombi, systemic hypotension, and organ failure.3)The presence and functional relevance of the kallikreinkinin system in the heart are firmly established. 4) Kinins, liberated by kallikrein from substrate kininogen, stimulate the release of NO and prostacyclin through the activation of bradykinin B 2 -receptor. This action opposes angiotensin II (Ang II)-induced vasoconstriction and exerts anti-ischemic, antiproliferative and antiatherosclerotic effects, preserving myocardial stores of energy-rich phosphates and glycogen. 5)Furthermore, stimulation of Ang II type 2 (AT 2 -) receptor present in myocardium attenuates the AT 1 -medicated cardiac hypertrophy and interstitial fibrosis through the B 2 -receptordependent mechanisms.6) The activation of B 2 -receptor in cardiac myocytes involves the cardioprotective effect of angiotensin-converting enzyme inhibitors and AT 1 -receptor antagonists in heart failure. 7)The presence of two subtypes of bradykinin receptors, B 1 -and B 2 -receptors, has been identified in the myocardium, 8) although B 1 -receptors are detectable after the induction of inflammation. LPS induces B 1 -receptors in the rat heart. 9)However, B 1 -receptor blockade does not attenuate the LPSinduced mortality.10) In contrast, it has been demonstrated that the administration of B 2 -receptor antagonists shows beneficial effects, i.e., increased survival rates and improved hemodynamic parameters in a model of endotoxin shock. [11][12][13][14] However, whether the expression of the B 2 -receptor in the heart is altered during sepsis is unknown. Therefore, the present study has been undertaken in mice to elucidate 1) whether the cardiac expression of B 2 -receptor mRNA is altered by LPS, and 2) which mediators are involved in the LPSinduced changes in cardiac B 2 -receptor mRNA expression. MATERIALS AND METHODS MaterialsThe following chemicals were obtained from commercial sources: LPS (Staphylococcus typhosa 0901) from Difco (Detroit, MI, U.S.A.); Ang II from Peptide Institute (Osaka, Japan); TNF-a, IL-1b and IL-6 from Sigma (St Louis, MO, U.S.A.), endothelin-1 (Nacalai Tesque); losartan (AT 1 -receptor antagonist; Funakoshi, Osaka, Japan), PD123319 (AT 2 -receptor antagonist; Wako Chemicals, Kyoto, Japan).Animal Treatment All animal experiments were performed according to the guidelines of the Kobe Gakuin University Experimental Animal Care and Use Committee. Male ddY mice, aged 6-8 weeks, 28-32 g (Japan SLC, Hamamatsu, Japan) were used in this study. Mice were injected with ...

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“…In most cells activation of TLR4 triggers expression of cell survival and inflammatory genes via NF-B-dependent mechanisms. Prolonged LPS treatment (16 -24 h) activates both pro-apoptotic and anti-apoptotic pathways in the heart (43) and induces very modest CM apoptosis (43,44). However, the low levels of apoptosis appear insuffi- .…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide Improves Cardiomyocyte Survival and Function after Serum Deprivation

Chao

Shen

Zhu

et al. 2005

Journal of Biological Chemistry

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Toll-like receptor-4 (TLR4) and its signaling molecule interleukin-1 receptor-associated kinase (IRAK-1) play an important role in host defense and tissue inflammation. Intriguingly, systemic administration of lipopolysaccharide (LPS), the agonist for TLR4, confers a cardio-protective effect against ischemic injury. However, the mechanisms leading to the cardiac protection remain largely unknown. The present study was designed to investigate the role of TLR4 activation by LPS in protecting cardiomyocytes (CM) against apoptosis in an in vitro model of ischemia and to explore the downstream mechanisms leading to the protective effect. Incubation with LPS led to activation of IRAK-1 and protected CMs against serum deprivation (SD)-induced apoptosis as demonstrated by DNA laddering, histone-DNA fragment enzyme-linked immunosorbent assay, and activation of caspase-3. Phosphatidylinositol 3-kinase/Akt, extracellular signal-regulated kinase 1/2, and IB kinase ␤ appear to contribute to the antiapoptotic effect of LPS since the specific inhibitors, wortmannin, PD98059, and dominant negative IKK␤ transgene expression reversed the LPS effect. To assess whether LPS improves CM function, we examined intracellular Ca 2؉ transients and cell shortening in single adult rat CMs. SD for 6 h dramatically inhibited Ca 2؉ transients and CM contractility. LPS at 500 ng/ml significantly improved the [Ca 2؉ ] i transients and enhanced contractility in control CMs as well as in CMs subjected to SD. Importantly, transient ischemia led to rapid activation of IRAK-1 in cultured CMs and in adult rat myocardium. Adenovirus-mediated transgene expression of IRAK-1 but not its kinase-deficient mutant IRAK-1(K239S) protected CMs against SD-induced apoptosis. Taken together, these data suggest an important role of TLR4 signaling via IRAK-1 in protecting against SD-induced apoptosis.Studies employing pharmacologic inhibitors, transgene expression, and genetically modified animals have demonstrated that cardiomyocyte (CM) 1 apoptosis plays an important role in ischemic myocardial injury (1-4). CM apoptosis has been found in injured myocardium in patients who died of myocardial infarction (5-7) and in animal models of infarction (8, 9) and ischemia reperfusion (10). Apoptosis is a tightly regulated and energy-dependent process that requires specialized cellular machinery. The central component of this machinery is a proteolytic system involving a family of proteases called caspases (11). The biochemical and cellular hallmarks of apoptosis are characterized by nuclear and DNA fragmentation and condensation, membrane blebbing, and cellular shrinkage.LPS signal transduction involves multiple signaling proteins such as LPS binding protein, CD14, MD-2, and TLR4. TLR4 dimerizes and becomes activated upon association with LPS⅐MD2⅐CD14 complex. Activated TLR4 recruits downstream the serine-threonine kinases, IRAKs, through the adapter protein MyD88. All IRAKs are multidomain proteins consisting of a conserved N-terminal death domain and a central kinase doma...

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Lipopolysaccharide induces apoptosis in adult rat ventricular myocytes via cardiac AT₁ receptors

Cited by 62 publications

References 43 publications

Increased Cardiac Adenylyl Cyclase Expression Is Associated With Increased Survival After Myocardial Infarction

Increased Cardiac Adenylyl Cyclase Expression Is Associated With Increased Survival After Myocardial Infarction

The Lipopolysaccharide-Induced Up-Regulation of Bradykinin B2-Receptor in the Mouse Heart Is Mediated by Tumor Necrosis Factor-.ALPHA. and Angiotensin II

Lipopolysaccharide Improves Cardiomyocyte Survival and Function after Serum Deprivation

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Lipopolysaccharide induces apoptosis in adult rat ventricular myocytes via cardiac AT1 receptors

Cited by 62 publications

References 43 publications

Increased Cardiac Adenylyl Cyclase Expression Is Associated With Increased Survival After Myocardial Infarction

Increased Cardiac Adenylyl Cyclase Expression Is Associated With Increased Survival After Myocardial Infarction

The Lipopolysaccharide-Induced Up-Regulation of Bradykinin B2-Receptor in the Mouse Heart Is Mediated by Tumor Necrosis Factor-.ALPHA. and Angiotensin II

Lipopolysaccharide Improves Cardiomyocyte Survival and Function after Serum Deprivation

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Lipopolysaccharide induces apoptosis in adult rat ventricular myocytes via cardiac AT₁ receptors