Targeting autophagy to modulate hepatic ischemia/reperfusion injury: A comparative study between octreotide and melatonin as autophagy modulators through AMPK/PI3K/AKT/mTOR/ULK1 and Keap1/Nrf2 signaling pathways in rats

Mohamed, Dina Zakaria; El‐Sisi, Alaa E.; Sokar, Samia Salem; Shebl, Abdelhadi M.; Abu-Risha, Sally El-Sayed

doi:10.1016/j.ejphar.2021.173920

Cited by 30 publications

(27 citation statements)

References 62 publications

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“…In a highly-nutrient state, mTOR is activated [ 35 ], which would fit with the fructose diet nutrient overload. Melatonin’s role in the mTOR pathway was not clarified and both activation and inhibition of the mTOR pathway were described in different contexts [ 36 , 37 ]. Melatonin treatment increased the mTOR activity in the regular chow-fed hamsters ( Figure 3 C, p < 0.01), which might be fostering the mTOR role in storing nutrients [ 38 ].…”

Section: Resultsmentioning

confidence: 99%

“…Melatonin might have a dual role depending on the cellular situation, when the cells are balanced, the melatonin activates the mTOR, which promotes the nutrient’s storage [ 38 ] as was observed by the Plin accumulation. However, when homeostasis is broken and oxidative stress levels are high, melatonin seems to activate autophagy and selective autophagy through mTOR inhibition [ 36 ], which would have a protective effect ( Figure 4 ).…”

Section: Resultsmentioning

confidence: 99%

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Melatonin Ameliorates Autophagy Impairment in a Metabolic Syndrome Model

et al. 2021

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Metabolic syndrome is a global health problem in adults and its prevalence among children and adolescents is rising. It is strongly linked to a lifestyle with high-caloric food, which causes obesity and lipid metabolism anomalies. Molecular damage due to excessive oxidative stress plays a major role during the development of metabolic syndrome complications. Among the different hormones, melatonin presents strong antioxidant properties, and it is used to treat metabolic diseases. However, there is not a consensus about its use as a metabolic syndrome treatment. The aim of this study was to identify melatonin effects in a metabolic syndrome model. Golden hamsters were fed with 60% fructose-enriched food to induce metabolic syndrome and were compared to hamsters fed with regular chow diet. Both groups were also treated with melatonin. Fructose-fed hamsters showed altered blood lipid levels (increased cholesterol and LDL) and phenotypes restored with the melatonin treatment. The Harderian gland (HG), which is an ideal model to study autophagy modulation through oxidative stress, was the organ that was most affected by a fructose diet. Redox balance was altered in fructose-fed HG, inducing autophagic activation. However, since LC3-II was not increased, the impairment must be in the last steps of autophagy. Lipophagy HG markers were also disturbed, contributing to the dyslipidemia. Melatonin treatment improved possible oxidative homeostasis through autophagic induction. All these results point to melatonin as a possible treatment of the metabolic syndrome.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Melatonin Ameliorates Autophagy Impairment in a Metabolic Syndrome Model

et al. 2021

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“…The activated MT1 receptor could also induce a transient increase in the concentrations of cytosolic calcium ions and inositol phosphate. In addition, studies have found that in the mouse ovaries, MT can up-regulate the intracellular AMPK signaling pathway through the MT1 receptor-mediated pathways [ 23 , 24 ]. The signals mediated by MT2 receptors are related to multiple pathways (including the activation of MT2 receptors to promote the production of phosphoinositol, as well as the inhibition of adenylate cyclase and guanylate cyclase), thereby regulating the downstream pathways to exert effects [ 23 , 24 ].…”

Section: Mt and Ovarian Functionsmentioning

confidence: 99%

“…In addition, studies have found that in the mouse ovaries, MT can up-regulate the intracellular AMPK signaling pathway through the MT1 receptor-mediated pathways [ 23 , 24 ]. The signals mediated by MT2 receptors are related to multiple pathways (including the activation of MT2 receptors to promote the production of phosphoinositol, as well as the inhibition of adenylate cyclase and guanylate cyclase), thereby regulating the downstream pathways to exert effects [ 23 , 24 ]. MT participates in the regulation of biological rhythms through a receptor-dependent mechanism, and promotes the coordination of tissues and organs [ 23 , 24 ].…”

Section: Mt and Ovarian Functionsmentioning

confidence: 99%

“…The signals mediated by MT2 receptors are related to multiple pathways (including the activation of MT2 receptors to promote the production of phosphoinositol, as well as the inhibition of adenylate cyclase and guanylate cyclase), thereby regulating the downstream pathways to exert effects [ 23 , 24 ]. MT participates in the regulation of biological rhythms through a receptor-dependent mechanism, and promotes the coordination of tissues and organs [ 23 , 24 ]. MT receptors exist in the human brain, cardiovascular system, liver, breast, and myometrium [ 17 ].…”

Section: Mt and Ovarian Functionsmentioning

confidence: 99%

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Research progress of melatonin (MT) in improving ovarian function: a review of the current status

Guo

Sun

Wang

et al. 2021

Aging

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Melatonin (MT) is an endogenous hormone mainly synthesized by pineal cells, which has strong endogenous effects of eliminating free radicals and resisting oxidative damages. Melatonin (MT) can not only regulate the body’s seasonal and circadian rhythms; but also delay ovarian senescence, regulate ovarian biological rhythm, promote follicles formation, and improve oocyte quality and fertilization rate. This review aimd to provide evidence concerning the synthesis and distribution, ovarian function, and role of MT in development of follicles and oocytes. Moreover, the role of MT as antioxidative, participating in biological rhythm regulation, was also reviewed. Furthermore, the effects of MT on various ovarian related diseases were analyzed, particularly for the ovarian aging and polycystic ovary syndrome (PCOS).

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AMPK: The key to ischemia‐reperfusion injury

Cai

Chen

Liu

et al. 2022

Journal Cellular Physiology

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Ischemia-reperfusion injury (IRI) refers to a syndrome in which tissue damage is further aggravated and organ function further deteriorates when blood flow is restored after a period of tissue ischemia. Acute myocardial infarction, stress ulcer, pancreatitis, intestinal ischemia, intermittent claudication, acute tubular necrosis, postshock liver failure, and multisystem organ failure are all related to reperfusion injury. AMP-activated protein kinase (AMPK) has been identified in multiple catabolic and anabolic signaling pathways. The functions of AMPK during health and diseases are intriguing but still need further research. Except for its conventional roles as an intracellular energy switch, emerging evidence reveals the critical role of AMPK in IRI as an energy-sensing signal molecule by regulating metabolism, autophagy, oxidative stress, inflammation, and other progressions. At the same time, drugs based on AMPK for the treatment of IRI are constantly being researched and applied in clinics. In this review, we summarize the mechanisms underlying the effects of AMPK in IRI and describe the AMPK-targeting drugs in treatment, hoping to increase the understanding of AMPK in IRI and provide new insights into future clinical treatment.

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Targeting autophagy to modulate hepatic ischemia/reperfusion injury: A comparative study between octreotide and melatonin as autophagy modulators through AMPK/PI3K/AKT/mTOR/ULK1 and Keap1/Nrf2 signaling pathways in rats

Cited by 30 publications

References 62 publications

Melatonin Ameliorates Autophagy Impairment in a Metabolic Syndrome Model

Melatonin Ameliorates Autophagy Impairment in a Metabolic Syndrome Model

Research progress of melatonin (MT) in improving ovarian function: a review of the current status

AMPK: The key to ischemia‐reperfusion injury

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