Activation of Akt by SC79 protects myocardiocytes from oxygen and glucose deprivation (OGD)/re-oxygenation

Zheng, Koulong; Zhang, Qing; Lin, Gang; Li, Yefei; Sheng, Zhenqiang; Wang, Jue; Chen, Liang; Lu, Hongzhou

doi:10.18632/oncotarget.14785

Cited by 39 publications

(51 citation statements)

References 44 publications

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“…Oxygen glucose deprivation (OGD)/re-oxygenation (OGDR) is often applied to cultured myocardial cells. In line with our previous findings [3][4][5], OGDR exposure in H9c2 cells (for 24 h) induced potent viability (MTT OD) reduction (Fig. 1C) and cell death (LDH medium release, Fig.…”

Section: Cntf Protects Myocardial Cells From Ogd/re-oxygenationsupporting

confidence: 93%

“…These results indicate that activation of Nrf2 is required for CNTF-induced cytoprotection against OGDR in H9c2 cells. Notably, in line with our previous findings [3,5], OGDR-induced cytotoxicity was augmented in Nrf2-silenced or -knockout H9c2 cells (Fig. 3C and D), further supporting a cytoprotective function of Nrf2 in OGDRtreated cells.…”

Section: Nrf2 Silencing or Knockout Abolishes C N T F -I N D U C E D supporting

confidence: 91%

“…OGDR mainly induces programmed necrosis, but not apoptosis, in myocardial cells and other cells [5,23,27,28]. Indeed, OGDR treatment in H9c2 cells induced programmed necrosis, which was evidenced by mitochondrial ANT-1-p53-Cyp-D association (Fig.…”

Section: Cntf Protects Myocardial Cells From Ogd/re-oxygenationmentioning

confidence: 86%

“…As previously discussed [5], cells were initially seeded onto 24-well tissue-culture plate at a density of 15, 000 cells per well. Following the applied treatment, cell death was determined by lactate dehydrogenase (LDH) assay via a commercial available LDH kit (Takara, Tokyo, Japan).…”

Section: Ldh Assay Of Cell Deathmentioning

confidence: 99%

“…The primers for rat HO-1, Nrf2, GAPDH, NQO-1 and GCLC were described previously [3]. The primers for murine HO-1, Nrf2, GAPDH, NQO-1 and GCLC were from Dr. Jiang's group [3,5,20,21]. mRNA primers for CNTF and CNTFR were designed and sequence verified by Genepharma (Shanghai, China).…”

Section: Real-time Pcrmentioning

confidence: 99%

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Ciliary Neurotrophic Factor (CNTF) Protects Myocardial Cells from Oxygen Glucose Deprivation (OGD)/Re-Oxygenation via Activation of Akt-Nrf2 Signaling

Zheng¹,

Zhang²,

Sheng³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Oxygen glucose deprivation (OGD)/re-oxygenation (OGDR) exposure to myocardial cells mimics ischemia-reperfusion injuries. We studied the potential activity of ciliary neurotrophic factor (CNTF) on OGDR-treated myocardial cells. Methods: CNTF and CNTFR expression were tested by RT-PCR assay and Western blotting assay. Cell viability and death were tested by MTT assay and LDH release assay, respectively. Akt-Nrf2 signalings were tested by Western blotting assay and qPCR assay. Results: CNTF and its receptor CNTFR were functionally expressed in established H9c2 myocardial cells and primary murine myocardiocytes. Pretreatment of CNTF significantly attenuated OGDR-induced viability reduction and death in myocardial cells. Further studies show that in the myocardial cells CNTF activated NF-E2-related factor 2 (Nrf2) signaling to inhibit OGDR-induced reactive oxygen species (ROS) production and programmed necrosis, preventing adenine nucleotide translocator 1 (ANT-1)-p53-cyclophilin D (Cyp-D) mitochondrial association and mitochondrial depolarization. Nrf2 silencing or knockout almost abolished CNTF-induced H9c2 cytoprotection against OGDR. CNTF activated Akt in H9c2 cells and primary murine myocardiocytes. Conversely, Akt blockage by the pharmacological inhibitors not only blocked CNTF-induced Nrf2 Ser-40 phosphorylation and activation, but also nullified anti-OGDR actions by CNTF in myocardial cells. Conclusion: CNTF activates Akt-Nrf2 signaling to protect myocardial cells from OGDR.

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Section: Cntf Protects Myocardial Cells From Ogd/re-oxygenationsupporting

confidence: 93%

Section: Nrf2 Silencing or Knockout Abolishes C N T F -I N D U C E D supporting

confidence: 91%

Section: Cntf Protects Myocardial Cells From Ogd/re-oxygenationmentioning

confidence: 86%

Section: Ldh Assay Of Cell Deathmentioning

confidence: 99%

Section: Real-time Pcrmentioning

confidence: 99%

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Ciliary Neurotrophic Factor (CNTF) Protects Myocardial Cells from Oxygen Glucose Deprivation (OGD)/Re-Oxygenation via Activation of Akt-Nrf2 Signaling

Zheng¹,

Zhang²,

Sheng³

et al. 2018

Cell Physiol Biochem

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FGF20‐FGFR1 signaling through MAPK and PI3K controls sensory progenitor differentiation in the organ of Corti

Yang

Ornitz

2020

Developmental Dynamics

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Background Fibroblast Growth Factor 20 (FGF20)‐FGF receptor 1 (FGFR1) signaling is essential for cochlear hair cell (HC) and supporting cell (SC) differentiation. In other organ systems, FGFR1 signals through several intracellular pathways including MAPK (ERK), PI3K, phospholipase C ɣ (PLCɣ), and p38. Previous studies implicated MAPK and PI3K pathways in HC and SC development. We hypothesized that one or both would be important downstream mediators of FGF20‐FGFR1 signaling for HC differentiation. Results By inhibiting pathways downstream of FGFR1 in cochlea explant cultures, we established that both MAPK and PI3K pathways are required for HC differentiation while PLCɣ and p38 pathways are not. Examining the canonical PI3K pathway, we found that while AKT is necessary for HC differentiation, it is not sufficient to rescue the Fgf20−/− phenotype. To determine whether PI3K functions downstream of FGF20, we inhibited Phosphatase and Tensin Homolog (PTEN) in Fgf20−/− explants. Overactivation of PI3K resulted in a partial rescue of the Fgf20−/− phenotype, demonstrating a requirement for PI3K downstream of FGF20. Consistent with a requirement for the MAPK pathway for FGF20‐regulated HC differentiation, we show that treating Fgf20−/− explants with FGF9 increased levels of dpERK. Conclusions Together, these data provide evidence that both MAPK and PI3K are important downstream mediators of FGF20‐FGFR1 signaling during HC and SC differentiation.

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Inhibition of PD-1 Alters the SHP1/2-PI3K/Akt Axis to Decrease M1 Polarization of Alveolar Macrophages in Lung Ischemia–Reperfusion Injury

Jingyuan

Zhao

et al. 2022

Inflammation

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Polarization of alveolar macrophages (AMs) into the M1 phenotype contributes to inflammatory responses and tissue damage that occur during lung ischemia–reperfusion injury (LIRI). Programmed cell death factor-1 (PD-1) regulates polarization of macrophages, but its role in LIRI is unknown. We examined the role of PD-1 in AM polarization in models of LIRI in vivo and in vitro. Adult Sprague–Dawley rats were subjected to ischemia–reperfusion with or without pretreatment with a PD-1 inhibitor, SHP1/2 inhibitor, or Akt activator. Lung tissue damage and infiltration by M1-type AMs were assessed. As an in vitro complement to the animal studies, rat alveolar macrophages in culture were subjected to oxygen/glucose deprivation and reoxygenation. Levels of SHP1/2 and Akt proteins were evaluated using Western blots, while levels of pro-inflammatory cytokines were measured using enzyme-linked immunosorbent assays. Injury upregulated PD-1 both in vivo and in vitro. Inhibiting PD-1 reduced the number of M1-type AMs, expression of SHP1 and SHP2, and levels of inflammatory cytokines. At the same time, it partially restored Akt activation. Similar results were observed after inhibition of SHP1/2 or activation of the PI3K/Akt pathway. PD-1 promotes polarization of AMs to the M1 phenotype and inflammatory responses through the SHP1/2-PI3K/Akt axis. Inhibiting PD-1 may be an effective therapeutic strategy to limit LIRI.

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Activation of Akt by SC79 protects myocardiocytes from oxygen and glucose deprivation (OGD)/re-oxygenation

Cited by 39 publications

References 44 publications

Ciliary Neurotrophic Factor (CNTF) Protects Myocardial Cells from Oxygen Glucose Deprivation (OGD)/Re-Oxygenation via Activation of Akt-Nrf2 Signaling

Ciliary Neurotrophic Factor (CNTF) Protects Myocardial Cells from Oxygen Glucose Deprivation (OGD)/Re-Oxygenation via Activation of Akt-Nrf2 Signaling

FGF20‐FGFR1 signaling through MAPK and PI3K controls sensory progenitor differentiation in the organ of Corti

Inhibition of PD-1 Alters the SHP1/2-PI3K/Akt Axis to Decrease M1 Polarization of Alveolar Macrophages in Lung Ischemia–Reperfusion Injury

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