scholarly journals The Neuroprotective Effects of Insulin-Like Growth Factor 1 via the Hippo/YAP Signaling Pathway is Mediated by the PI3K/AKT Pathway Following Cerebral Ischemia-Reperfusion Injury

2021 ◽  
Author(s):  
Pian Gong ◽  
Yichun Zou ◽  
Wei Zhang ◽  
Qi Tian ◽  
Shoumeng Han ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Neuronal Death ◽  
Infarct Volume ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Neuroprotective Effects

Abstract Insulin-like growth factor 1 (IGF-1) exhibits neuroprotective properties, such as vasodilatory and anti-inflammatory effects following ischemic stroke. However, the specific molecular mechanisms of action of IGF-1 following ischemic stroke remain elusive. We wanted to explore whether IGF-1 regulates Hippo/YAP signaling pathway, potentially via activation of the PI3K/AKT signaling pathway to exert its neuroprotective effects following ischemic stroke. In the in vitro study, we used oxygen–glucose deprivation to injure cultured PC12 and SH-5YSY cells, and cortical primary neurons. Cell viability was measured using CCK-8 assay. For the in vivo analyses, Sprague–Dawley rats were subjected to middle cerebral artery occlusion; neurological function was assessed using the neurological deficit score; infarct volume was measured using triphenyltetrazolium chloride staining, and neuronal death and apoptosis was evaluated by TUNEL staining, H&E staining and Nissl staining. Western blot was used to measure the levels of YAP/TAZ, PI3K and phosphorylated AKT (p-AKT) both in vitro and in vivo. We found that IGF-1 induced activation of YAP/TAZ, which resulted in improved cell viability in vitro, and decreased neurological deficits, neuronal death and apoptosis, and cerebral infarct volume in vivo. Notably, the neuroprotective effects of IGF-1 were reversed by an inhibitor of the PI3K/AKT signaling pathway, LY294002, which not only reduced expressions of PI3K and p-AKT, but also down-regulated expression of YAP/TAZ, leading to aggravation of neurological dysfunction. These findings indicate that neuroprotective effect of IGF-1 is partly realized by up-regulation of YAP/TAZ, which is mediated by activation of the PI3K/AKT signaling pathway following cerebral ischemic stroke.

A77 1726 (leflunomide) blocks and reverses cardiac hypertrophy and fibrosis in mice

2018 ◽  
Vol 132 (6) ◽  
pp. 685-699 ◽  
Author(s):  
Zhen-Guo Ma ◽  
Xin Zhang ◽  
Yu-Pei Yuan ◽  
Ya-Ge Jin ◽  
Ning Li ◽  
...  
Keyword(s):  
T Cell ◽  
Cardiac Hypertrophy ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Cardiac Fibrosis ◽  
Pressure Overload ◽  
Akt Signaling ◽  
Akt Signaling Pathway

T-cell infiltration and the subsequent increased intracardial chronic inflammation play crucial roles in the development of cardiac hypertrophy and heart failure (HF). A77 1726, the active metabolite of leflunomide, has been reported to have powerful anti-inflammatory and T cell-inhibiting properties. However, the effect of A77 1726 on cardiac hypertrophy remains completely unknown. Herein, we found that A77 1726 treatment attenuated pressure overload or angiotensin II (Ang II)-induced cardiac hypertrophy in vivo, as well as agonist-induced hypertrophic response of cardiomyocytes in vitro. In addition, we showed that A77 1726 administration prevented induction of cardiac fibrosis by inhibiting cardiac fibroblast (CF) transformation into myofibroblast. Surprisingly, we found that the protective effect of A77 1726 was not dependent on its T lymphocyte-inhibiting property. A77 1726 suppressed the activation of protein kinase B (AKT) signaling pathway, and overexpression of constitutively active AKT completely abolished A77 1726-mediated cardioprotective effects in vivo and in vitro. Pretreatment with siRNA targetting Fyn (si Fyn) blunted the protective effect elicited by A77 1726 in vitro. More importantly, A77 1726 was capable of blocking pre-established cardiac hypertrophy in mice. In conclusion, A77 1726 attenuated cardiac hypertrophy and cardiac fibrosis via inhibiting FYN/AKT signaling pathway.

Knockdown of Nrf2 inhibits angiogenesis by downregulating VEGF expression through PI3K/Akt signaling pathway in cerebral microvascular endothelial cells under hypoxic conditions

2018 ◽  
Vol 96 (4) ◽  
pp. 475-482 ◽  
Author(s):  
Yujing Huang ◽  
Ying Mao ◽  
Huiying Li ◽  
Guangxun Shen ◽  
Guangxian Nan
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Ischemic Stroke ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Tube Formation ◽  
Vascular Endothelial ◽  
Akt Signaling Pathway ◽  
Microvascular Endothelial ◽  
Endothelial Growth Factor

Ischemic stroke is a major cerebrovascular disease resulting from a transient or permanent local reduction of cerebral blood flow. Angiogenesis plays an important role in cerebral microvascular repair after ischemic stroke. This study aimed at investigating the effect of NF-E2-related factor 2 (Nrf2) on the angiogenesis of mouse cerebral microvascular endothelial bEnd.3 cells in a hypoxic environment. We found that Nrf2 expression was temporarily increased in hypoxia-induced bEnd.3 cells. Knockdown of Nrf2 inhibited the proliferation, migration, as well as tube formation in hypoxia-induced bEnd.3 cells. Meanwhile, vascular endothelial growth factor and PI3K/Akt signaling pathways were identified to be regulated by Nrf2 in hypoxia-induced bEnd.3 cells. It was found that silencing of Nrf2 downregulated the expression levels of NAD(P)H:quinine oxidoreductase-1, vascular endothelial growth factor, p-Akt, and heme oxygenase-1 in hypoxia-induced bEnd.3 cells. Data suggested that hypoxia induced the transient increase of Nrf2, which plays a key role in the angiogenesis of cerebral microangiogenesis, and that Nrf2 regulates the proliferation, migration, as well as tube formation likely through PI3K/Akt signaling pathway in hypoxia-induced bEnd.3 cells. Our study provides proof of concept for the modulation of Nrf2, so as to tilt the balance toward angiogenesis, representing a therapeutic strategy for hypoxia or ischemia disorders such as stroke.

Cyanidin inhibits EMT induced by oxaliplatinviatargeting the PDK1–PI3K/Akt signaling pathway

2019 ◽  
Vol 10 (2) ◽  
pp. 592-601 ◽  
Author(s):  
Xiang Li ◽  
Ze-sheng Zhang ◽  
Xiao-han Zhang ◽  
Sheng-nan Yang ◽  
Dong Liu ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Signaling Pathway

Anthocyanins have been shown to exhibit antitumor activity in several cancersin vitroandin vivo.

scholarly journals Luteolin Exerts Cardioprotective Effects through Improving Sarcoplasmic Reticulum Ca2+-ATPase Activity in Rats during Ischemia/Reperfusion In Vivo

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Changsheng Nai ◽  
Haochen Xuan ◽  
Yingying Zhang ◽  
Mengxiao Shen ◽  
Tongda Xu ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Signaling Pathway ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Myocardial Infarct Size ◽  
Akt Signaling Pathway ◽  
Cardioprotective Effects

The flavonoid luteolin exists in many types of fruits, vegetables, and medicinal herbs. Our previous studies have demonstrated that luteolin reduced ischemia/reperfusion (I/R) injury in vitro, which was related with sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity. However, the effects of luteolin on SERCA2a activity during I/R in vivo remain unclear. To investigate whether luteolin exerts cardioprotective effects and to monitor changes in SERCA2a expression and activity levels in vivo during I/R, we created a myocardial I/R rat model by ligating the coronary artery. We demonstrated that luteolin could reduce the myocardial infarct size, lactate dehydrogenase release, and apoptosis during I/R injury in vivo. Furthermore, we found that luteolin inhibited the I/R-induced decrease in SERCA2a activity in vivo. However, neither I/R nor luteolin altered SERCA2a expression levels in myocardiocytes. Moreover, the PI3K/Akt signaling pathway played a vital role in this mechanism. In conclusion, the present study has confirmed for the first time that luteolin yields cardioprotective effects against I/R injury by inhibiting the I/R-induced decrease in SERCA2a activity partially via the PI3K/Akt signaling pathway in vivo, independent of SERCA2a protein level regulation. SERCA2a activity presents a novel biomarker to assess the progress of I/R injury in experimental research and clinical applications.

scholarly journals Sphingadienes show therapeutic efficacy in neuroblastoma in vitro and in vivo by targeting the AKT signaling pathway

2018 ◽  
Vol 36 (5) ◽  
pp. 743-754 ◽  
Author(s):  
Piming Zhao ◽  
Ana E. Aguilar ◽  
Joanna Y. Lee ◽  
Lucy A. Paul ◽  
Jung H. Suh ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Therapeutic Efficacy ◽  
Akt Signaling ◽  
Akt Signaling Pathway

PTEN improve renal fibrosis in vitro and in vivo through inhibiting FAK/AKT signaling pathway

2019 ◽  
Vol 120 (10) ◽  
pp. 17887-17897 ◽  
Author(s):  
Yongchao Du ◽  
Peihua Liu ◽  
Zhi Chen ◽  
Yao He ◽  
Bo Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Renal Fibrosis ◽  
Akt Signaling ◽  
Akt Signaling Pathway

scholarly journals Autophagy is Involved in Neuroprotective Effect of Alpha7 Nicotinic Acetylcholine Receptor on Ischemic Stroke

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhe-Qi Xu ◽  
Jing-Jing Zhang ◽  
Ni Kong ◽  
Guang-Yu Zhang ◽  
Ping Ke ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Autophagy Flux ◽  
Nicotinic Acetylcholine

The α7 nicotinic acetylcholine receptor (α7nAChR) belongs to the superfamily of cys loop cationic ligand-gated channels, which consists of homogeneous α7 subunits. Although our lab found that activation of α7nAChR could alleviate ischemic stroke, the mechanism is still unknown. Herein, we explored whether autophagy is involved in the neuroprotective effect mediated by α7nAChR in ischemic stroke. Transient middle cerebral artery occlusion (tMCAO) and oxygen and glucose deprivation (OGD/R) exposure were applied to in vivo and in vitro models of ischemic stroke, respectively. Neurological deficit score and infarct volume were used to evaluate outcomes of tMCAO in the in vivo study. Autophagy-related proteins were detected by Western blot, and autophagy flux was detected by using tandem fluorescent mRFP-GFP-LC3 lentivirus. At 24 h after tMCAO, α7nAChR knockout mice showed worse neurological function and larger infarct volume than wild-type mice. PNU282987, an α7nAChR agonist, protected against OGD/R-induced neuronal injury, enhanced autophagy, and promoted autophagy flux. However, the beneficial effects of PNU282987 were eliminated by 3-methyladenine (3-MA), an autophagy inhibitor. Moreover, we found that PNU282987 treatment could activate the AMPK-mTOR-p70S6K signaling pathway in the in vitro study, while the effect was attenuated by compound C, an AMPK inhibitor. Our results demonstrated that the beneficial effect on neuronal survival via activation of α7nAChR was associated with enhanced autophagy, and the AMPK-mTOR-p70S6K signaling pathway was involved in α7nAChR activation–mediated neuroprotection.

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