Rutin from Lonicera japonica inhibits myocardial ischemia/reperfusion-induced apoptosis in vivo and protects H9c2 cells against hydrogen peroxide-mediated injury via ERK1/2 and PI3K/Akt signals in vitro

Jeong, Jae Ju; Ha, Yu Mi; Jin, Yong; Lee, Eun Ju; Kim, Ju Sun; Kim, Hye Jung; Seo, Han Geuk; Lee, Jae Heun; Kang, Sam Sik; Kim, Yeung Shik; Chang, Ki Churl

doi:10.1016/j.fct.2009.03.044

Cited by 83 publications

(45 citation statements)

References 31 publications

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“…Moreover, LD-IGF-1-treated animals exhibited concurrent activation signaling downstream of the IGF-1 receptor, with phosphorylation of PI3K/Akt, GSK-3␤, and ERK, supporting prosurvival pathways affecting both membrane pore transition and caspase pathways. It has been well described previously that inhibition of caspase activation occurs at least in part through phosphorylation of Akt and ERK, 26,27 so it is likely that the reduction in infarct-related cardiomyocyte death seen in the LD-IGF-1-treated group was mediated through activation of these pathways. Similarly, phosphorylation and, thus, inhibition of GSK-3␤ in the infarct region 30 minutes after LD-IGF-1 may reduce activation of discrete signals essential for cardiomyocyte cell death and necrosis.…”

Section: Discussionmentioning

confidence: 99%

Potent Long-Term Cardioprotective Effects of Single Low-Dose Insulin-Like Growth Factor-1 Treatment Postmyocardial Infarction

O’Sullivan

Leblond

Kelly

et al. 2011

Circ: Cardiovascular Interventions

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Background-Insulin-like growth factor-1 (IGF-1) is recognized as an important regulator of cardiac structure and cardiomyocyte homeostasis. The prosurvival and antiapoptotic effects of IGF-1 have been investigated in vitro and in rodent models of myocardial infarction (MI). However, the clinical application of IGF-1 has been hampered by dose-dependent side effects both acutely and during chronic administration. We hypothesized that single, low-dose IGF-1 (LD-IGF-1) administered locally and early in the reperfusion phase after acute MI in a large animal model would avoid significant side effects but would have prosurvival effects that would manifest in long-term structural and functional improvement after MI treatment. Methods and Results-Forty-four female Landrace pigs underwent intracoronary administration of LD-IGF-1 or saline 2 hours into the reperfusion phase of acute left anterior descending artery occlusion MI. In the area of infarction, IGF-1 receptor and signaling responses were activated at 30 minutes and cardiomyocyte cell death attenuated at 24 hours after LD-IGF-1 but not saline treatment. Hemodynamic and structural studies using pressure-volume loop, CT, and triphenyltetrazolium chloride analysis 2 months post-MI confirmed a marked reduction in infarct size, attenuation of wall thinning, and augmentation of wall motion in the LD-IGF-1-treated but not in the saline-treated animals. These regional structural benefits were associated with global reductions in left ventricular volumes and significant improvement in left ventricular systolic and diastolic function. Conclusions-One-time LD-IGF-1 effects potent acute myocardial salvage in a preclinical model of left anterior descending artery occlusive MI, extending to long-term benefits in MI size, wall structure, and function and underscoring its potential as an adjunctive therapeutic agent. (Circ Cardiovasc Interv. 2011;4:327-335.)

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Section: Discussionmentioning

confidence: 99%

Potent Long-Term Cardioprotective Effects of Single Low-Dose Insulin-Like Growth Factor-1 Treatment Postmyocardial Infarction

O’Sullivan

Leblond

Kelly

et al. 2011

Circ: Cardiovascular Interventions

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“…H9c2 cardiomyoblasts have been widely used to screen active components (31,32). To investigate the potency of new inhibitors on MIRI, H/R and H 2 O 2 -induced cell injury models are often used in vitro (33)(34)(35)(36)(37). Therefore, the two models were also used in our study to evaluate the protective effects of bpV(pic) and bpV(phen).…”

Section: Discussionmentioning

confidence: 99%

Effects of bpV(pic) and bpV(phen) on H9c2 cardiomyoblasts during both hypoxia/reoxygenation and H2O2-induced injuries

2011

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Abstract. Reactive oxygen species (ROS) are involved in myocardial injury. ROS are known to inactivate lipid phosphatase and tension homolog on chromosome 10 (PTEN), an enzyme that increases apoptosis in neonatal cardiomyocytes. BpV(pic) and bpV(phen), two bisperoxovanadium molecules and PTEN inhibitors, may be involved in limiting myocardial infarction. To compare the protective effects of bpV(pic) and bpV(phen) on ROS-induced cardiomyocyte injury and their possible mechanisms, we selected two popular models of hypoxia/reoxygenation (H/R) and H 2 O 2 -induced injury in H9c2 cardiomyoblasts to investigate their effects against injury. We found that pre-treatment with bpV(pic) and bpV(phen) increased the viability and protected the morphology of H9c2 cells under the conditions of H/R and H 2 O 2 by inhibiting LDH release, apoptosis and caspases 3/8/9 activities. However, their respective inhibitory abilities in the two models were different, suggesting that the quantity of ROS from the two models might be different. However, the conflict between ROS and PTEN may affect the action of bpV(pic) and bpV(phen). Taken together, the results demonstrate that bpV(pic) and bpV(phen) have inhibitory effects on oxidative stress-induced cardiomyocyte injury that may be partially modulated by the action of ROS on PTEN. IntroductionMyocardial ischemia/reperfusion injury (MIRI), which may lead to various complications, including myocardial infarction, cardiac contractile dysfunction and arrhythmia (1-4), has become an increasingly common problem in clinics. However, few strategies directed against MIRI have been tested under clinical conditions (5,6). Recently, a new finding showed that the pharmacological inhibition of lipid phosphatase and tension homolog on chromosome 10 (PTEN) limited myocardial infarct size and improved left ventricular function post-infarction (7). Moreover, protein tyrosine phosphatase inhibitors and bisperoxovanadium molecules (bpV) inhibited PTEN specifically at low concentrations (8). The protective effects of bpV(HOpic) on myocardial injury in vitro and in vivo have been observed in previous studies (7). However, other bpV molecules have not been studied and compared for their actions against MIRI.Based on the cellular mechanisms of ischemia/reperfusion injury that have been extensively explored (9-11), reactive oxygen species (ROS) generated with the re-admission of oxygen are considered the first and main cause of ischemia/ reperfusion injury (12). Thus, scavenging excessive ROS and restoring the reduction-oxidation (redox) balance in the body is an important strategy in inhibiting reperfusion injury, as the redox balance is the solid physiological condition in humans from birth (13,14), and, despite evolution, this balance has always been conserved in all organisms (15,16).Hydrogen dioxide (H 2 O 2 ), a famous ROS, inhibits the lipid phosphatase activity of the tumour suppressor PTEN enzyme (17), which suggests that when produced under pathological conditions, such as during MIRI or chronic inflamm...

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“…The antioxidant action of Que may contribute to this modulation (32), since many antioxidants affect the expression of Bcl-2 family proteins during myocardial I/R (33,34). Alternatively, activation of PI3K/Akt may be responsible for the changes in Bcl-2 and Bax expression (35).…”

Section: Discussionmentioning

confidence: 99%

Quercetin postconditioning attenuates myocardial ischemia/reperfusion injury in rats through the PI3K/Akt pathway

Wang

Zhang

et al. 2013

Braz J Med Biol Res

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Quercetin (Que), a plant-derived flavonoid, has multiple benefical actions on the cardiovascular system. The current study investigated whether Que postconditioning has any protective effects on myocardial ischemia/reperfusion (I/R) injury in vivo and its potential cardioprotective mechanisms. Male Sprague-Dawley rats were randomly allocated to 5 groups (20 animals/group): sham, I/R, Que postconditioning, Que+LY294002 [a phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway inhibitor], and LY294002+I/R. I/R was produced by 30-min coronary occlusion followed by 2-h reperfusion. At the end of reperfusion, myocardial infarct size and biochemical changes were compared. Apoptosis was evaluated by both TUNEL staining and measurement of activated caspase-3 immunoreactivity. The phosphorylation of Akt and protein expression of Bcl-2 and Bax were determined by Western blotting. Que postconditioning significantly reduced infarct size and serum levels of creatine kinase and lactate dehydrogenase compared with the I/R group (all P<0.05). Apoptotic cardiomyocytes and caspase-3 immunoreactivity were also suppressed in the Que postconditioning group compared with the I/R group (both P<0.05). Akt phosphorylation and Bcl-2 expression increased after Que postconditioning, but Bax expression decreased. These effects were inhibited by LY294002. The data indicate that Que postconditioning can induce cardioprotection by activating the PI3K/Akt signaling pathway and modulating the expression of Bcl-2 and Bax proteins.

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Rutin from Lonicera japonica inhibits myocardial ischemia/reperfusion-induced apoptosis in vivo and protects H9c2 cells against hydrogen peroxide-mediated injury via ERK1/2 and PI3K/Akt signals in vitro

Cited by 83 publications

References 31 publications

Potent Long-Term Cardioprotective Effects of Single Low-Dose Insulin-Like Growth Factor-1 Treatment Postmyocardial Infarction

Potent Long-Term Cardioprotective Effects of Single Low-Dose Insulin-Like Growth Factor-1 Treatment Postmyocardial Infarction

Effects of bpV(pic) and bpV(phen) on H9c2 cardiomyoblasts during both hypoxia/reoxygenation and H2O2-induced injuries

Quercetin postconditioning attenuates myocardial ischemia/reperfusion injury in rats through the PI3K/Akt pathway

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