Capsid protein from red-spotted grouper nervous necrosis virus induces incomplete autophagy by inactivating the HSP90ab1-AKT-MTOR pathway

Zhang, Wanwan; Jia, Peng; Lu, Xiaobing; Chen, Xiaoqi; Weng, Juehua; Yi, Meisheng

doi:10.24272/j.issn.2095-8137.2021.249

Cited by 17 publications

(9 citation statements)

References 48 publications

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“…However, SWAP70 expression showed no obvious change after the treatment with chloroquine or MG132 in the presence of cycloheximide and phenylephrine compared with the control group (Figure 2D ), suggesting that the increased SWAP70 protein expression after phenylephrine treatment can be ascribed to its reduced lysosomal degradation. To explore the possible upstream molecule(s) involved in the lysosomal regulation of SWAP70 protein expression, we performed protein mass spectrometry, intersected it with a subcellular localization database ( https://compartments.jensenlab.org/Search ) by bioinformatics to find the molecules that can colocalize with lysosomes (9 molecules remained after this step), and finally used a protein database ( https://www.uniprot.org ) to inquire about the function of these 9 molecules and gained 3 of them that were reported to involve in the regulation of molecular degradation 31 , 32 , 33 (Figure 2E ). Further experiments in human embryonic kidney 293T cells transfected with the indicated molecules suggested that granulin precursor (GRN) regulated the lysosomal degradation of SWAP70 (Figure 2F ).…”

Section: Resultsmentioning

confidence: 99%

SWAP70 Overexpression Protects Against Pathological Cardiac Hypertrophy in a TAK1‐Dependent Manner

Qian

et al. 2023

JAHA

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Background Pathological cardiac hypertrophy is regarded as a critical precursor and independent risk factor of heart failure, and its inhibition prevents the progression of heart failure. Switch‐associated protein 70 (SWAP70) is confirmed important in immunoregulation, cell maturation, and cell transformation. However, its role in pathological cardiac hypertrophy remains unclear. Methods and Results The effects of SWAP70 on pathological cardiac hypertrophy were investigated in Swap70 knockout mice and Swap70 overexpression/knockdown cardiomyocytes. Bioinformatic analysis combined with multiple molecular biological methodologies were adopted to elucidate the mechanisms underlying the effects of SWAP70 on pathological cardiac hypertrophy. Results showed that SWAP70 protein levels were significantly increased in failing human heart tissues, experimental transverse aortic constriction–induced mouse hypertrophic hearts, and phenylephrine‐stimulated isolated primary cardiomyocytes. Intriguingly, phenylephrine treatment decreased the lysosomal degradation of SWAP70 by disrupting the interaction of SWAP70 with granulin precursor. In vitro and in vivo experiments revealed that Swap70 knockdown/knockout accelerated the progression of pathological cardiac hypertrophy, while Swap70 overexpression restrained the cardiomyocyte hypertrophy. SWAP70 restrained the binding of transforming growth factor β‐activated kinase 1 (TAK1) and TAK1 binding protein 1, thus blocking the phosphorylation of TAK1 and downstream c‐Jun N‐terminal kinase/P38 signaling. TAK1 interacted with the N‐terminals (1–192) of SWAP70. Swap70 (193–585) overexpression failed to inhibit cardiac hypertrophy when the TAK1–SWAP70 interaction was disrupted. Either inhibiting the phosphorylation or suppressing the expression of TAK1 rescued the exaggerated cardiac hypertrophy induced by Swap70 knockdown. Conclusions SWAP70 suppressed the progression of cardiac hypertrophy, possibly by inhibiting the mitogen‐activated protein kinases signaling pathway in a TAK1‐dependent manner, and lysosomes are involved in the regulation of SWAP70 expression level.

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Section: Resultsmentioning

confidence: 99%

SWAP70 Overexpression Protects Against Pathological Cardiac Hypertrophy in a TAK1‐Dependent Manner

Qian

et al. 2023

JAHA

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“…A recent study in L. japonicus brain (LJB) cells shows that CP blocks the interaction of AKT with HSP90ab1 by the competitive binding with HSP90ab1 to inhibit the AKT-mTOR pathway. 109 Moreover, grass carp reovirus (GCRV) infection evokes autophagy activation by eliciting ROS accumulation in Ctenopharyngodon idella kidney (CIK) cells. In this process, HSP70 promotes high-mobility group box 1b (HMGB1b)-Beclin1-mediated antiviral autophagy.…”

Section: Modulation Of Autophagy By Aquatic Rna Virusesmentioning

confidence: 99%

“…More deeply, the major autophagy‐inducing peptides of the G of VHSV and IHNV were identified by a pepscan technique 112 . A recent study shows that the N‐terminal arginine‐rich motif (N‐ARM, residue 1–33), arm (residue 34–51) and linker region (LR) domains of capsid protein (CP) are sufficient for red grouper nervous necrosis virus (RGNNV) to induce autophagy 109 . It is suggested that these protein regions could be a crucial target for the development of antiviral agents.…”

Section: The Roles Of Autophagy In Aquatic Animal Virus Infectionmentioning

confidence: 99%

Autophagy regulation of virus infection in aquatic animals

Zhang

Zhao

et al. 2023

Reviews in Aquaculture

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Autophagy is a conserved intracellular degradation process that is required to maintain host homeostasis and cope with invading pathogens. Over the past few decades, studies on mammals have greatly increased our understanding of the relationship between autophagy and virus infection. Autophagy may convey the invader to lysosomes to degrade or activate the host immune response against virus replication. However, many viruses have developed some strategies that evade the degradative nature of autophagy or hijack this pathway for their gain. It follows that autophagy during viral infection is a double‐edged sword. In contrast to mammals, the review on autophagy modulated by the aquatic animal virus is limited. Here, after a brief description of the main information about autophagy, we highlight current progress on the interplays between autophagy and virus infection in aquatic animals, including the phenomenon of autophagy upon virus infection, the effect of modulating autophagy on virus replication, and the crosstalk between autophagy and immune response during virus infection. This review will help us better understand the pathogenic mechanism of aquatic animal viruses and develop proper antiviral countermeasures aimed at modulating autophagy.

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“…Several studies have shown that lithium inhibits inositol monophosphatase and decreases the synthesis of inositol triphosphate, thereby regulating protein kinase B (AKT) to promote cell growth, proliferation, and anabolism ( Hermida et al, 2017 ; Malhi & Outhred, 2016 ; Zhang et al, 2022 ). Moreover, lithium has been shown to enhance AKT phosphorylation and inhibit glycogen synthase kinase-3 (GSK-3) ( Beaulieu et al, 2004 ; Liu et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Chronic lithium treatment ameliorates ketamine-induced mania-like behavior via the PI3K-AKT signaling pathway

Ni¹,

Gao²,

Wang³

et al. 2022

Zoological Research

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Ketamine, a rapid-acting antidepressant drug, has been used to treat major depressive disorder and bipolar disorder (BD). Recent studies have shown that ketamine may increase the potential risk of treatment-induced mania in patients. Ketamine has also been applied to establish animal models of mania. At present, however, the underlying mechanism is still unclear. In the current study, we found that chronic lithium exposure attenuated ketamine-induced mania-like behavior and c-Fos expression in the medial prefrontal cortex (mPFC) of adult male mice. Transcriptome sequencing was performed to determine the effect of lithium administration on the transcriptome of the PFC in ketamine-treated mice, showing inactivation of the phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway. Pharmacological inhibition of AKT signaling by MK2206 (40 mg/kg), a selective AKT inhibitor, reversed ketamine-induced mania. Furthermore, selective knockdown of AKT via AAV-AKT-shRNA-EGFP in the mPFC also reversed ketamine-induced mania-like behavior. Importantly, pharmacological activation of AKT signaling by SC79 (40 mg/kg), an AKT activator, contributed to mania in low-dose ketamine-treated mice. Inhibition of PI3K signaling by LY294002 (25 mg/kg), a specific PI3K inhibitor, reversed the mania-like behavior in ketamine-treated mice. However, pharmacological inhibition of mammalian target of rapamycin (mTOR) signaling with rapamycin (10 mg/kg), a specific mTOR inhibitor, had no effect on ketamine-induced mania-like behavior. These results suggest that chronic lithium treatment ameliorates ketamine-induced mania-like behavior via the PI3K-AKT signaling pathway, which may be a novel target for the development of BD treatment.

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Capsid protein from red-spotted grouper nervous necrosis virus induces incomplete autophagy by inactivating the HSP90ab1-AKT-MTOR pathway

Cited by 17 publications

References 48 publications

SWAP70 Overexpression Protects Against Pathological Cardiac Hypertrophy in a TAK1‐Dependent Manner

SWAP70 Overexpression Protects Against Pathological Cardiac Hypertrophy in a TAK1‐Dependent Manner

Autophagy regulation of virus infection in aquatic animals

Chronic lithium treatment ameliorates ketamine-induced mania-like behavior via the PI3K-AKT signaling pathway

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