Isorhamnetin Attenuates Atherosclerosis by Inhibiting Macrophage Apoptosis via PI3K/AKT Activation and HO-1 Induction

Luo, Yun; Sun, Guibo; Xi, Dong; Wang, Min; Qin, Meng; Yu, Yingli; Sun, Xiaobo

doi:10.1371/journal.pone.0120259

Cited by 79 publications

(73 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[17][18][19] Many investigations have discovered that IsoRN has many biological activities such as antiinflammatory, antitumor, and cardioprotective effects. [20][21][22] Consistent with previous studies, 23,24 we have shown in the current study that IsoRN exerts protective effects against the A/R-induced cardiomyocyte injury indicated by a significant increase in cell viability and decrease in LDH and CPK released, reduction of the ROS generation, preservation of mitochondrial membrane potential, inhibition of mPTP opening, reduction of cytosol cytochrome c, inactivation of caspase-3, and ultimate decrease in cardiomyocyte apoptosis. Furthermore, coadministration of the SIRT1 inhibitor sirtinol has been found to block the protective effects of IsoRN on cardiomyocytes.…”

Section: Discussionsupporting

confidence: 91%

Protective Effects of Isorhamnetin on Cardiomyocytes Against Anoxia/Reoxygenation-induced Injury Is Mediated by SIRT1

Huang

Liu

et al. 2016

Journal of Cardiovascular Pharmacology

View full text Add to dashboard Cite

It has been reported that apoptosis plays a very important role on anoxia/reoxygenation (A/R)-induced injury, and human silent information regulator type 1 (SIRT1) can inhibit the apoptosis of cardiomyocytes. It has been proved that isorhamnetin (IsoRN), 3'-O-methyl-quecetin, can protect the cardiomyocytes, but the mechanism is still not clear. The aim of the study was to explore whether the protective effects of IsoRN on the cardiomyocytes against the A/R-induced injury are mediated by SIRT1. The effects of IsoRN on cardioprotection against A/R injury in neonatal rat cardiomyocytes were monitored by cell viability, the levels of mitochondrial membrane potential (Δψm), apoptosis, and intracellular reactive oxygen species (ROS), the levels of lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and mitochondrial permeability transition pores (mPTP). The effects on protein expression were measured by western blot assay. The results showed that IsoRN can reduce A/R-induced injury by decreasing the level of lactate dehydrogenase and creatine phosphokinase release from the cardiomyocytes, increasing cell viability and expression of SIRT1, reducing the generation of reactive oxygen species, inhibiting opening of mitochondrial permeability transition pores and loss of Δψm and activation of caspase-3, and decreasing the release of cytochrome c, and reducing apoptosis. In addition, sirtinol, a SIRT1 inhibitor, drastically reduced the protective effects of IsoRN on cardioprotective effects in cardiomocytes. In conclusion, we firstly demonstrated that SIRT1 may be involved in the protective effects of IsoRN on cardiomocytes against the A/R-induced injury.

show abstract

Section: Discussionsupporting

confidence: 91%

Protective Effects of Isorhamnetin on Cardiomyocytes Against Anoxia/Reoxygenation-induced Injury Is Mediated by SIRT1

Huang

Liu

et al. 2016

Journal of Cardiovascular Pharmacology

View full text Add to dashboard Cite

show abstract

“…As our results suggested, this is the first report to reveal that HO-1 upregulation in in vivo and in vitro studies could play an indirect a role in mitochondrial fusion protein Mfn1 expression in LPS-induced ALI rats and alveolar macrophages. In addition, we further demonstrated that the possible mechanism might be due to PI3K/Akt pathway activation3435, which has an effective impact on regulating HO-1 upregulation. Thus, our findings offer a new insight into the role of HO-1 in attenuating oxidative stress through the mitochondrial fusion protein Mfn1, which greatly contributes to further clarification of the mechanism of HO-1 protection against oxidative stress and provides opportunities for designing mitochondria-targeted HO-1 interventions for ALI/ARDS treatment.…”

Section: Discussionmentioning

confidence: 72%

Effect of Heme Oxygenase-1 on Mitofusin-1 protein in LPS-induced ALI/ARDS in rats

Wang

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common and important oxidative stress in the lung. Mitochondrial fusion responds to the normal morphology and function of cells and is finely regulated by mitochondrial fusion proteins, such as mitofusin-1 protein (Mfn1), mitofusin-2 protein (Mfn2) and optical atrophy 1 (OPA1). Additionally, Mfn1 has been identified as the most important protein in mitochondrial fusion. Heme oxygenase-1 (HO-1) is a stress-inducible protein that plays a critical role in protecting against oxidative stress. However, whether the protection of HO-1 is related to mitochondrial fusion is still a question. Thus, our in vitro and in vivo experiments aimed to identify the relationship between HO-1 and Mfn1. Here, we used Hemin and ZnPP-IX as treatments in an in vivo experiment. Then, HO-1 and Mfn1 were measured using RT-PCR and Western blotting. Supernatants were analyzed for MDA, SOD, and ROS. Our results implied that HO-1 upregulation suppressed oxidative stress induced by LPS, and the possible mechanism could be associated with Mfn1 and the PI3K/Akt pathway.

show abstract

“…Mannitol (33.3 mM) was added to the cultures to rule out the effect of high osmolarity ( Figure 1A). H9c2 cell viability was detected by the MTT method as described previously [39]. The MTT cell viability OD value was detected using a microplate reader (MQX 200, BioTek Instruments, Winooski, VT, USA).…”

Section: Establishment Of a High Glucose Model: Screening The Myricitmentioning

confidence: 99%

Myricitrin Attenuates High Glucose-Induced Apoptosis through Activating Akt-Nrf2 Signaling in H9c2 Cardiomyocytes

et al. 2016

Self Cite

View full text Add to dashboard Cite

Hyperglycemia, as well as diabetes mellitus, has been shown to trigger cardiac cell apoptosis. We have previously demonstrated that myricitrin prevents endothelial cell apoptosis. However, whether myricitrin can attenuate H9c2 cell apoptosis remains unknown. In this study, we established an experiment model in H9c2 cells exposed to high glucose. We tested the hypothesis that myricitrin may inhibit high glucose (HG)-induced cardiac cell apoptosis as determined by TUNEL staining. Furthermore, myricitrin promoted antioxidative enzyme production, suppressed high glucose-induced reactive oxygen species (ROS) production and decreased mitochondrial membrane potential (MMP) in H9c2 cells. This agent significantly inhibited apoptotic protein expression, activated Akt and facilitated the transcription of NF-E2-related factor 2 (Nrf2)-mediated protein (heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO-1) expression as determined by Western blotting. Significantly, an Akt inhibitor (LY294002) or HO-1 inhibitor (ZnPP) not only inhibited myricitrin-induced HO-1/NQO-1 upregulation but also alleviated its anti-apoptotic effects. In summary, these observations demonstrate that myricitrin activates Nrf2-mediated anti-oxidant signaling and attenuates H9c2 cell apoptosis induced by high glucose via activation of Akt signaling.

show abstract

Isorhamnetin Attenuates Atherosclerosis by Inhibiting Macrophage Apoptosis via PI3K/AKT Activation and HO-1 Induction

Cited by 79 publications

References 45 publications

Protective Effects of Isorhamnetin on Cardiomyocytes Against Anoxia/Reoxygenation-induced Injury Is Mediated by SIRT1

Protective Effects of Isorhamnetin on Cardiomyocytes Against Anoxia/Reoxygenation-induced Injury Is Mediated by SIRT1

Effect of Heme Oxygenase-1 on Mitofusin-1 protein in LPS-induced ALI/ARDS in rats

Myricitrin Attenuates High Glucose-Induced Apoptosis through Activating Akt-Nrf2 Signaling in H9c2 Cardiomyocytes

Contact Info

Product

Resources

About