Spermidine ameliorates liver ischaemia-reperfusion injury through the regulation of autophagy by the AMPK-mTOR-ULK1 signalling pathway

Líu, Hao; Dong, Jia-yong; Shen, Song; Zhao, Yuanyu; Wang, Jiyuan; Fu, Zhiren; Yang, Jinghui

doi:10.1016/j.bbrc.2019.08.162

Cited by 28 publications

(19 citation statements)

References 22 publications

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“…6 In this regard, our previous studies showed that autophagy induction in response to stressful conditions during the phase of reperfusion plays a vital role in maintaining organ function. 7,8 Therefore, autophagy is an appealing target for regulating and normalizing imbalances during IR injury.…”

Section: Introductionmentioning

confidence: 99%

“…Conversely, insufficient autophagy not only compromises cellular energy metabolism, but also leads to the release of excessive ROS and pro‐apoptotic factors, which ultimately cause cell death 6 . In this regard, our previous studies showed that autophagy induction in response to stressful conditions during the phase of reperfusion plays a vital role in maintaining organ function 7,8 . Therefore, autophagy is an appealing target for regulating and normalizing imbalances during IR injury.…”

Section: Introductionmentioning

confidence: 99%

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Melatonin pretreatment alleviates renal ischemia‐reperfusion injury by promoting autophagic flux via TLR4/MyD88/MEK/ERK/mTORC1 signaling

et al. 2020

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Autophagy is an important mechanism for cellular homeostasis and survival during pathologic stress conditions in the kidney, such as ischemia‐reperfusion (IR) injury. In this study, renal IR was induced in female C57BL/6 mice after melatonin administration. Renal function, histological damage, inflammatory infiltration, cytokine production, oxidative stress, antioxidant capacity, autophagy changing, apoptosis levels, and autophagy‐associated intracellular signaling pathway were assessed to evaluate the impact of antecedent melatonin treatment on IR‐induced renal injury. The administration of melatonin resulted in significantly preserved renal function, and the protective effect was associated with ameliorated oxidative stress, limited pro‐inflammatory cytokine production, and neutrophil and macrophage infiltration. Moreover, autophagic flux was increased after melatonin administration while the apoptosis levels were decreased in the melatonin‐pretreated mice. Using TAK‐242 and CRX‐527, we confirmed that MyD88‐dependent TLR4 and MEK/ERK/mTORC1 signaling participated in melatonin‐induced autophagy in IR mice. Collectively, our results provide novel evidence that antecedent melatonin treatment provides protection for the kidney against IR injury by enhancing autophagy, as regulated by the TLR4/MyD88/MEK/ERK/mTORC1 signaling pathway. Therefore, melatonin preconditioning offers a potential therapeutic approach to prevent renal IR injury related to various clinical conditions.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Melatonin pretreatment alleviates renal ischemia‐reperfusion injury by promoting autophagic flux via TLR4/MyD88/MEK/ERK/mTORC1 signaling

et al. 2020

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“…SAHA-mediated amelioration of liver injury depends on KC autophagy. Published studies have shown that autophagy plays a controversial role in liver ischemia reperfusion injury (11,(46)(47)(48); therefore, the present study investigated the role of autophagy in the protective effect of SAHA on OLT-induced IRI by using the autophagy inhibitor CQ. The increased levels of serum ALT and serum AST in the CQ-treated group indicated that inhibition of autophagy partly impaired the protective effect of SAHA on OLT-induced IRI (Fig.…”

Section: Sa H a Inhibits Kc M1 Polarization Through The Akt/gsk3β/nf-mentioning

confidence: 99%

Suberoylanilide hydroxamic acid alleviates orthotopic liver transplantation‑induced hepatic ischemia‑reperfusion injury by regulating the AKT/GSK3β/NF‑κB and AKT/mTOR pathways in rat Kupffer cells

Wang

Deng

et al. 2020

Int J Mol Med

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Multiple mechanisms are involved in regulating hepatic ischemia-reperfusion injury (IRI), in which Kupffer cells (Kcs), which are liver-resident macrophages, play critical roles by regulating inflammation and the immune response. Suberoylanilide hydroxamic acid (SAHA), a pan-histone deacetylase inhibitor, has anti-inflammatory effects and induces autophagy. To investigate whether SAHA ameliorates IRI and the mechanisms by which SAHA exerts its effects, an orthotopic liver transplantation (OLT) rat model was established after treatment with SAHA. The results showed that SAHA effectively ameliorated OLT-induced IRI by reducing M1 polarization of Kcs through inhibition of the AKT/glycogen synthase kinase (GSK)3β/NF-κB signaling pathway. Furthermore, the present study found that SAHA upregulates autophagy 5 protein (ATG5)/Lc3B in Kcs through the AKT/mTOR signaling pathway and inhibition of autophagy by knockdown of ATG5 in Kcs partly impaired the protective effect of SAHA on IR-injured liver. Therefore, the current study demonstrated that SAHA reduces M1 polarization of Kcs by inhibiting the AKT/GSK3β/NF-κB pathway and upregulates autophagy in Kcs through the AKT/mTOR signaling pathway, which both alleviate OLT-induced IRI. The present study revealed that SAHA may be a novel treatment for the amelioration of OLT-induced IRI.

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“…Spermidine is a known inducer of autophagy (262,273) and has been shown to be an effective antiaging agent (274 -276). Spermidine induces autophagy by inducing the synthesis of the autophagy transcription factor TFEB (277) through the AMPK-mTORC1-ULK1 pathway (273). It was shown to provide cardioprotection and to extend life in mice through activation of autophagy and mitophagy (275).…”

Section: Lifespan and Healthspan Extension Paradigms And Mptpmentioning

confidence: 99%

The Mitochondrial Permeability Transition: Nexus of Aging, Disease and Longevity

Rottenberg¹,

Hoek²

2020

Preprint

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The activity of the mitochondrial Permeability Transition Pore, mPTP, a highly regulated multi-component mega-channel, is enhanced in aging and in aging-driven degenerative diseases. mPTP activity accelerates aging by releasing large amounts of cell-damaging Reactive Oxygen Species, Ca2+ and NAD+. The various pathways that control the channel activity, directly or indirectly, can therefore either, inhibit, or accelerate aging, retards, or enhance the progression of aging-driven degenerative diseases, and determine lifespan and healthspan. Autophagy, a catabolic process that removes and digests damaged proteins and organelles protects the cell against aging and disease. However, the protective effect of autophagy depends on mTORC2/SKG1 inhibition of mPTP. Autophagy is inhibited in aging cells. Mitophagy, a specialized form of autophagy, which retards aging by removing mitochondrial fragments with activated mPTP, is also inhibited in aging cells, and this inhibition leads to increased mPTP activation, which is a major contributor to neurodegenerative diseases, such as Alzheimer’s and Parkinson’s Diseases. The Increased activity of mPTP in aging turns autophagy/mitophagy into a destructive process leading to cell aging and death. Several drugs and lifestyle modifications that enhance healthspan and lifespan enhance autophagy and inhibit the activation of mPTP. Therefore, elucidating the intricate connections between pathways that activate and inhibit mPTP, in the context of aging and degenerative diseases, could enhance the discovery of new drugs and lifestyle modifications that slow aging and degenerative disease.

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Spermidine ameliorates liver ischaemia-reperfusion injury through the regulation of autophagy by the AMPK-mTOR-ULK1 signalling pathway

Cited by 28 publications

References 22 publications

Melatonin pretreatment alleviates renal ischemia‐reperfusion injury by promoting autophagic flux via TLR4/MyD88/MEK/ERK/mTORC1 signaling

Melatonin pretreatment alleviates renal ischemia‐reperfusion injury by promoting autophagic flux via TLR4/MyD88/MEK/ERK/mTORC1 signaling

Suberoylanilide hydroxamic acid alleviates orthotopic liver transplantation‑induced hepatic ischemia‑reperfusion injury by regulating the AKT/GSK3β/NF‑κB and AKT/mTOR pathways in rat Kupffer cells

The Mitochondrial Permeability Transition: Nexus of Aging, Disease and Longevity

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