Mild hypothermia pretreatment extenuates liver ischemia-reperfusion injury through Rab7-mediated autophagosomes-lysosomes fusion

Liu, Anxiong; Wang, Wei; Lu, Zhongshan; Liu, Zhongzhong; Wei, Zhou; Zhong, Zibiao; Ye, Qifa

doi:10.1016/j.bbrc.2021.02.125

Cited by 6 publications

(13 citation statements)

References 24 publications

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“…44 Liver ischemic-reperfusion injury is an unavoidable pathological process in LT, closely related poor graft survival. 45 In mouse model, administration of rapamycin before ischemicreperfusion injury enhanced autophagy flux, and deteriorating liver damage. 45 Hence, STX17 expression may be involved in autophagy flux, and deteriorate ischemic-reperfusion damage, which needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…Starvation inhibits VAMP8 phosphorylation, and promotes STX17‐SNAP29‐VAMP8 SNARE complex formation and autophagy flux 44 . Liver ischemic‐reperfusion injury is an unavoidable pathological process in LT, closely related poor graft survival 45 . In mouse model, administration of rapamycin before ischemic‐reperfusion injury enhanced autophagy flux, and deteriorating liver damage 45 .…”

Section: Discussionmentioning

confidence: 99%

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Low syntaxin 17 expression in donor liver is associated with poor graft prognosis in recipients of living donor liver transplantation

Tomiyama

Shimokawa

Harada

et al. 2022

Hepatology Research

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Aim Liver transplantation (LT) is the only curative therapy for decompensated liver cirrhosis. For recipients of living donor LT (LDLT), restoration of liver function after transplantation is highly dependent on liver regenerative capacity, which requires large amounts of intracellular energy. Mitochondrial metabolism provides a stable supply of adenosine 5′‐triphosphate (ATP) for liver regeneration. Mitophagy is a selective process in which damaged, non‐functional mitochondria are degraded and replaced with new functional mitochondria. We investigated the relationship between expression of Syntaxin17 (STX17), a key protein in mitophagy regulation, in donor livers and graft survival. Methods We examined STX17 expression in grafts from 143 LDLT donors who underwent right lobe resection and investigated the relationship between STX17 expression and graft function. We investigated the correlations among STX17 expression, mitochondrial membrane potential and cell proliferation, using a STX17‐knockdown hepatocyte cell line. Results Recipients transplanted with low STX17‐expression grafts had significantly lower graft survival rates than recipients transplanted with high STX17‐expression grafts (88.9% vs. 100%, p < 0.01). Multivariate analysis showed that low STX17 expression (HR: 10.7, CI: 1.29–88.0, p < 0.05) and the absence of splenectomy (HR: 6.27, CI: 1.59–24.8, p < 0.01) were independent predictive factors for small‐for‐size graft syndrome, which is the severe complication in LDLT. In the vitro experiments, the percentage of depolarized damaged mitochondria was increased in the STX17‐knockdown hepatocyte cell line, suggesting decreased mitophagy and ATP synthesis. Cell proliferation was significantly decreased in the STX17‐knockdown hepatocyte cell line. Conclusion STX17 contributes to mitophagy and maintenance of mitochondrial function in hepatocytes and may be a predictor of graft dysfunction in LDLT patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Low syntaxin 17 expression in donor liver is associated with poor graft prognosis in recipients of living donor liver transplantation

Tomiyama

Shimokawa

Harada

et al. 2022

Hepatology Research

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“…Conversely, a deacetylation of FOXO1 promotes its nuclear import, and also enables it to drive the transcription of the gene coding for the G protein Rab7 [46,47]. The latter plays an essential role in enabling the fusion of late autophagosomes with lysosomes, a crucial step in autosomal flux [48,49].…”

Section: Roles Of Atf4 Chop and Foxo1 In Autophagymentioning

confidence: 99%

Nutraceutical and Dietary Strategies for Up-Regulating Macroautophagy

McCarty

2022

IJMS

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Macroautophagy is a “cell cleansing” process that rids cells of protein aggregates and damaged organelles that may contribute to disease pathogenesis and the dysfunctions associated with aging. Measures which boost longevity and health span in rodents typically up-regulate macroautophagy, and it has often been suggested that safe strategies which can promote this process in humans may contribute to healthful aging. The kinase ULK1 serves as a trigger for autophagy initiation, and the transcription factors TFEB, FOXO1, ATF4 and CHOP promote expression of a number of proteins which mediate macroautophagy. Nutraceutical or dietary measures which stimulate AMPK, SIRT1, eIF5A, and that diminish the activities of AKT and mTORC1, can be expected to boost the activities of these pro-autophagic factors. The activity of AMPK can be stimulated with the phytochemical berberine. SIRT1 activation may be achieved with a range of agents, including ferulic acid, melatonin, urolithin A, N1-methylnicotinamide, nicotinamide riboside, and glucosamine; correction of ubiquinone deficiency may also be useful in this regard, as may dietary strategies such as time-restricted feeding or intermittent fasting. In the context of an age-related decrease in cellular polyamine levels, provision of exogenous spermidine can boost the hypusination reaction required for the appropriate post-translational modification of eIF5A. Low-protein plant-based diets could be expected to increase ATF4 and CHOP expression, while diminishing IGF-I-mediated activation of AKT and mTORC1. Hence, practical strategies for protecting health by up-regulating macroautophagy may be feasible.

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“…Therapeutic hypothermia (TH) involves controlling the decrease of core temperature to lessen the secondary organ injury that occurs after the primary injury (5). Mild TH (32°C-35°C) protects brain nerve function (6) and attenuate IRI of organs, such as the liver and kidney (7)(8)(9). However, quickly cooling of the human body to target temperature is challenging.…”

Section: Introductionmentioning

confidence: 99%

Mild therapeutic hypothermia reduces ischemia-reperfusion injury following Zone 1 REBOA in a swine hemorrhagic shock model

Yang,

Jianxin,

Chengcheng

et al. 2023

Shock

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Background Resuscitative balloon occlusion of the aorta (REBOA) is an endovascular hemostasis method used for the management of traumatic abdominal and pelvic hemorrhages. However, REBOA-associated ischemia-reperfusion injury (IRI) complication limits its blocking time. We hypothesized that mild therapeutic hypothermia (TH) would relieve IRI caused by prolonged zone 1 REBOA. Methods Ten pigs were anesthetized, intubated, and subsequently struck with the experimental sliding-chamber ballistic gun to inflict liver damage. Animals were randomized to hypothermia (60 min of Zone 1 REBOA with external cooling for 180 min, n = 5) or control (60 min of Zone 1 REBOA with no external cooling, n = 5). Physiological and laboratory parameters were monitored and assessed. Distal organs were obtained for histologic analysis. Results At 180 min, compared with the control, the hypothermia animals exhibited significantly increased pH and significantly reduced lactate (Lac), hemoglobin (Hb) and hematocrit (Hct) (all p < 0.05). The change of Lac from 0 to 180 min in hypothermia animals was less than that in the control (p = 0.02). The total bleeding in the control group was significantly less than the hypothermia (p < 0.01). In the hypothermia group, PT at 120 and 180 min was significantly longer than that at baseline (all p < 0.05). Compared with the control, animals in hypothermia group showed slighter pathological injury of the distal organs and significantly lower overall injury score (all p < 0.05). Conclusions Mild TH during prolonged Zone 1 REBOA offered extraordinary distal organ preservation, and decreased metabolic acidosis.

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Mild hypothermia pretreatment extenuates liver ischemia-reperfusion injury through Rab7-mediated autophagosomes-lysosomes fusion

Cited by 6 publications

References 24 publications

Low syntaxin 17 expression in donor liver is associated with poor graft prognosis in recipients of living donor liver transplantation

Low syntaxin 17 expression in donor liver is associated with poor graft prognosis in recipients of living donor liver transplantation

Nutraceutical and Dietary Strategies for Up-Regulating Macroautophagy

Mild therapeutic hypothermia reduces ischemia-reperfusion injury following Zone 1 REBOA in a swine hemorrhagic shock model

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