Alpinetin inhibits macrophage infiltration and atherosclerosis by improving the thiol redox state: Requirement of GSk3β/Fyn‐dependent Nrf2 activation

Dong, Doudou; Zhang, Yun; He, Hui; Zhu, Yuan; Ou, Hailong

doi:10.1096/fj.202101567r

Cited by 11 publications

(6 citation statements)

References 49 publications

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“…MMP2 has been implicated in the remodelling of the ECM to assist trophoblast cell invasion, and a previous study showed that enhancing MMP-2/9 activity could promote trophoblast cell invasion and migration [26]. Remarkably, Fyn was reported to facilitate cell invasion and migration by regulating MMP2 and MMP9 [27,28], which was in line with our results. MMP-2/9 activity was inhibited by knockdown of Fyn, which in turn was promoted by overexpression of Fyn.…”

Section: Discussionsupporting

confidence: 92%

Regulatory Effects of Fyn on Trophoblast Cell Behaviors and Function

Liu

Ding

Xie

2022

BioMed Research International

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Fyn has been proven to be involved in various cell behaviors and pathophysiological processes. However, the expression and roles of Fyn in trophoblasts remain unclear. Here, we aimed to evaluate the participation of Fyn in trophoblast behavior and function, and the related mechanisms were briefly explored. Fyn expression in the HTR-8/SVneo, JEG-3, and JAR cell lines was evaluated by immunofluorescence, quantitative real-time PCR and western blotting. Fyn expression in human hydatidiform moles was also determined by immunohistochemistry and western blot. To explore the effects of Fyn, HTR-8/SVneo and JEG-3 cells were transfected with Fyn shRNA or overexpression plasmid or treated with the Fyn activity inhibitor SU6656 or ERK1/2 inhibitor U0126. The migration, proliferation, and apoptosis of trophoblast cells were assessed using transwell assays, flow cytometry, and cell counting kit-8 assays, respectively. The production of primary inflammatory cytokines, HLA-G and active matrix metallopeptidase (MMP) 2/9, and the phosphorylation of ERK1/2 and STAT3 were evaluated by ELISA, western blot, or gelatin zymography. The results showed that Fyn was expressed by trophoblast cells, mainly in the cytoplasm and membrane. Fyn expression and activity levels both increased in order from HTR-8/SVneo and JAR to JEG-3. The overexpression of Fyn promoted the proliferation and migration of trophoblast cells and inhibited their apoptosis, while the opposite effects were observed for Fyn knockdown and inhibition. Fyn regulated inflammatory cytokine production in trophoblast cells by promoting TGF-β and IL-4 secretion while inhibiting IFN-γ and TNF-α secretion. Moreover, HLA-G expression in JEG-3 was positively regulated by Fyn. Fyn also facilitated the expression of active MMP2/9 and the activation of ERK1/2 and STAT3. Besides, it was confirmed that Fyn regulated trophoblast cell activities through ERK1/2 signal pathway by using U0126. Our study first detected the expression of Fyn in trophoblast cells. Fyn played pivotal roles in trophoblast cell behaviors and function, ERK1/2 was one of its targets, and MMP2/9 and STAT3 may also be involved in the regulatory mechanism.

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Section: Discussionsupporting

confidence: 92%

Regulatory Effects of Fyn on Trophoblast Cell Behaviors and Function

Liu

Ding

Xie

2022

BioMed Research International

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“…This finding was in line with a study that reported that AKT inactivation was closely involved in the process of DOX-induced cardiotoxicity [ 33 ]. AKT inactivation resulted in GSK3 β /FYN activation, thus promoting the nuclear exclusion of Nrf2 and its degradation in cytoplasm [ 34 ]. Here, we also reported that DOX decreased Nrf2 expression, and Mul treatment restored Nrf2 protein expression.…”

Section: Discussionmentioning

confidence: 99%

Mulberrin Confers Protection against Doxorubicin-Induced Cardiotoxicity via Regulating AKT Signaling Pathways in Mice

Bao

et al. 2022

Oxidative Medicine and Cellular Longevity

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Doxorubicin (DOX) is an antitumor anthracycline, but its clinical use was largely limited by its cardiac toxicity. DOX-induced oxidative damage and cardiomyocyte loss have been recognized as the potential causative mechanisms of this cardiac toxicity. Growing interests are raised on mulberrin (Mul) for its wide spectrum of biological activities, including antioxidative and anti-inflammatory properties. The aim of this study was to investigate the effect of Mul on DOX-induced heart injury and to clarify the underlying mechanism. Mice were given daily 60 mg/kg of Mul via gavage for 10 days. Mice received an intraperitoneal injection of DOX to mimic the model of DOX-related acute cardiac injury at the seventh day of Mul treatment. Mul-treated mice had an attenuated cardiac injured response and improved cardiac function after DOX injection. DOX-induced oxidative damage, inflammation accumulation, and myocardial apoptosis were largely attenuated by the treatment of Mul. Activated protein kinase B (AKT) activation was essential for the protective effects of Mul against DOX-induced cardiac toxicity, and AKT inactivation abolished Mul-mediated protective effects against DOX cardiotoxicity. In conclusion, Mul treatment attenuated DOX-induced cardiac toxicity via activation of the AKT signaling pathway. Mul might be a promising therapeutic agent against DOX-induced cardiac toxicity.

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“…For example, diarylheptanoids yakuchinone A ( 4) and 5 0 -hydroxyyakuchinone A (5) scavenged reactive oxygen species (ROS) in HepG cells. 50 Moreover, 13-hydroxynootkatone (155) and nootkatone-11,12-epoxide (162) from A. oxyphylla effectively repaired the damage from tert-butyl hydroperoxide-induced oxidative stress in adipose-derived mesenchymal stem cells in a dose-dependent manner. 4 Coriandralpinins A-H (67-74) isolated from A. coriandriodora also exerted ROS inhibition in a dose-dependent manner.…”

Section: Anti-oxidant Effectsmentioning

confidence: 99%