HO-1 Activation Can Attenuate Cardiomyocytic Apoptosis via Inhibition of NF-κB and AP-1 Translocation Following Cardiac Global Ischemia and Reperfusion

Yeh, Chi-Hsiao; Chen, Tzu-Ping; Wang, Yao-Chang; Lin, Yu‐Min; Lin, Pyng Jing

doi:10.1016/j.jss.2008.07.044

Cited by 51 publications

(32 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phosphorylation of c-Jun is its most important regulatory mechanism, and enhances c-Jun/AP-1 transcriptional activity [27]. Recent studies reveal that AP-1 may induce apoptosis of cardiac cells and are involved in the pathologic conditions of MIRI [28]. TLR4, P38MAPK, and AP-1 signaling pathways have all been shown to be up-regulated in the liver following I/R injury [11].…”

Section: Discussionmentioning

confidence: 99%

RP105 Protects Against Apoptosis in Ischemia/Reperfusion-Induced Myocardial Damage in Rats by Suppressing TLR4-Mediated Signaling Pathways

Yang

Guo

Yang

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: Myocardial apoptosis is heavily implicated in the myocardial damage caused by ischemia-reperfusion (I/R). Toll-like receptor 4 (TLR4) is a potent inducer of these apoptotic cascades. In contrast, the radioprotective 105 kDa protein (RP105) is a specific negative regulator of TLR4 signaling pathways. However, the precise mechanisms by which RP105 inhibits myocardium apoptosis via TLR4-associated pathways during I/R is not fully understood. Methods: We utilized a rat model of myocardial ischemic reperfusion injury (MIRI). Animals were pre-treated with Ad-EGFP adenovirus, Ad-EGFP-RP105 adenovirus, saline, or nothing (sham). After three days, rats underwent a 30min left anterior descending coronary artery occlusion and a 4h reperfusion. Mycardial tissue was assessed by immunohistochemistry, TUNEL-staining, Western blot, quantitative RT-PCR, and a morphometric assay. Results: RP105 overexpression resulted in a reduction in infarct size, fewer TUNEL-positive cardiomyocytes, and a reduction in mitochondrial-associated apoptosis cascade activity. Further, RP105 overexpression repressed I/R-induced myocardial injury by attenuating myocardial apoptosis. This was mediated by inhibiting TLR4 activation and the phosphorylation of P38MAPK and the downstream transcription factor AP-1. Conclusion: RP105 overexpression leads to the de-activation of TLR4, P38MAPK, and AP-1 signaling pathways, and subsequently represses apoptotic cascades and ensuing damage of myocardial ischemic reperfusion. These findings may become the basis of a novel therapeutic approach for reducing of cardiac damage caused by MIRI.

show abstract

Section: Discussionmentioning

confidence: 99%

RP105 Protects Against Apoptosis in Ischemia/Reperfusion-Induced Myocardial Damage in Rats by Suppressing TLR4-Mediated Signaling Pathways

Yang

Guo

Yang

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…In previous experiments with leukemia cells, it was also demonstrated that HO-1 expression contributes to apoptosis mediated by oxidative stress [29]. However, in a model of cardiac ischemia and reperfusion, HO-1 has been described to attenuate cardiomyocytic apoptosis [30] by reducing NF-κB and AP-1 nuclear translocation, thereby reducing the level of caspase-3 activation and the surge of inflammatory cytokines [31]. On the other hand, more recent findings showed additional deleterious effects of HO-1 by proving that systemic HO-1 overexpression aggravates pressure overload-induced cardiac hypertrophy [32].…”

Section: Discussionmentioning

confidence: 99%

Heme Oxygenase-1 Mediates Oxidative Stress and Apoptosis in Coxsackievirus B3-Induced Myocarditis

Ursu¹,

Sauter²,

Ettischer³

et al. 2014

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: Heme oxygenase-1 (HO-1), which is suggested to play a role in defending the organism against oxidative stress-mediated injuries, can be induced by diverse factors including viruses and iron. As coxsackievirus B3 (CVB3)-infected SWR/J mice susceptible for chronic myocarditis were found to have a significant iron incorporation and HO-1 upregulation in the myocardium, we aimed to investigate the molecular interplay between HO-1 expression and iron homeostasis in the outcome of viral myocarditis. Methods and Results: In susceptible SWR/J mice, but not in resistant C57BL/6 mice, we observed at later stages of CVB3 myocarditis significant iron deposits in macrophages and also in cardiomyocytes, which were spatially associated with oxidative stress, upregulation of HO-1 and caspase-3 activation. HO-1, which is also expressed in cultivated RAW 264.7 macrophages upon incubation with iron and/or CVB3, could be downregulated by inhibition of NO/iNOS using L-NAME. Moreover, specific inhibition of HO-1 by tin mesoporphyrin revealed a suppression of superoxide production in iron and/or CVB3-treated macrophages. The molecular relationship of HO-1 and caspase-3 activation was proven by downregulation with HO-1 siRNA in iron- and/or CVB3-treated cultivated cells. Importantly, iron was found to increase viral replication in vitro. Conclusion: These results indicate that HO-1 induces a paracrine signalling in macrophages via reactive oxygen species production, mediating apoptosis of heart muscle cells at later stages of myocarditis. Notably, in genetically susceptible mice iron potentiates the detrimental effects of CVB3 by the NO/HO-1 pathway, thus increasing cardiac pathogenicity.

show abstract

“…NF-κB and AP-1 act in association for regulating cellular apoptosis. HO-1 has been found to block production of inflammatory cytokines and induction of NF-κB and AP-1 in response to stressful stimuli, thus preventing apoptosis [43,44]. Recent studies suggest that HO-1 mediate its anti-apoptotic effects by suppressing TNF/TNF receptor-1 mediated apoptotic signaling [45].The anti-apoptotic effect of HO-1 might be derived in a crucial manner from CO generation which contributes greatly to its overall protective effect.…”

Section: Anti-apoptotic Properties Of Ho-1mentioning

confidence: 99%

Heme oxygenase-1, a novel target for the treatment of diabetic complications: focus on diabetic peripheral neuropathy

Negi

Nakkina

Kamble

et al. 2015

Pharmacological Research

View full text Add to dashboard Cite

HO-1 Activation Can Attenuate Cardiomyocytic Apoptosis via Inhibition of NF-κB and AP-1 Translocation Following Cardiac Global Ischemia and Reperfusion

Cited by 51 publications

References 29 publications

RP105 Protects Against Apoptosis in Ischemia/Reperfusion-Induced Myocardial Damage in Rats by Suppressing TLR4-Mediated Signaling Pathways

RP105 Protects Against Apoptosis in Ischemia/Reperfusion-Induced Myocardial Damage in Rats by Suppressing TLR4-Mediated Signaling Pathways

Heme Oxygenase-1 Mediates Oxidative Stress and Apoptosis in Coxsackievirus B3-Induced Myocarditis

Heme oxygenase-1, a novel target for the treatment of diabetic complications: focus on diabetic peripheral neuropathy

Contact Info

Product

Resources

About