Neuroprotective effects of irisin against cerebral ischemia/ reperfusion injury via Notch signaling pathway

Jin, Zhao; Guo, Peipei; Li, Xinyi; Ke, Jianjuan; Wang, Yanlin; Wu, Huisheng

doi:10.1016/j.biopha.2019.109452

Cited by 84 publications

(61 citation statements)

References 38 publications

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“…To investigate the mechanism underlying how r-irisin increased osteoblast differentiation, we analyzed signaling pathways which irisin regulated based on reported studies, and found that irisin could modulate Notch [43], focal adhesion kinase (FAK) -extracellular signal-regulated kinase (Erk) -mitogen-activated protein (MAP) [23,25,44,45], reactive oxygen species (ROS) [46,47], phosphatidylinositol-3-kinase (PI3K) -v-akt murine thymoma viral oncogene homolog 1(AKT) [48], and Wnt/β-catenin [27,37,45] signaling pathways. Significantly, it is reported that irisin inhibited adipogenesis through regulating the Wnt/β-catenin signaling pathway [37].…”

Section: Discussionmentioning

confidence: 99%

Recombinant Irisin Prevents the Reduction of Osteoblast Differentiation Induced by Stimulated Microgravity through Increasing β-Catenin Expression

Chen

Zhang

Zhao

et al. 2020

IJMS

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Background: Irisin, a novel exercise-induced myokine, was shown to mediate beneficial effects of exercise in osteoporosis. Microgravity is a major threat to bone homeostasis of astronauts during long-term spaceflight, which results in decreased bone formation. Methods: The hind-limb unloading mice model and a random position machine are respectively used to simulate microgravity in vivo and in vitro. Results: We demonstrate that not only are bone formation and osteoblast differentiation decreased, but the expression of fibronectin type III domain-containing 5 (Fdnc5; irisin precursor) is also downregulated under simulated microgravity. Moreover, a lower dose of recombinant irisin (r-irisin) (1 nM) promotes osteogenic marker gene (alkaline phosphatase (Alp), collagen type 1 alpha-1(ColIα1)) expressions, ALP activity, and calcium deposition in primary osteoblasts, with no significant effect on osteoblast proliferation. Furthermore, r-irisin could recover the decrease in osteoblast differentiation induced by simulated microgravity. We also find that r-irisin increases β-catenin expression and partly neutralizes the decrease in β-catenin expression induced by simulated microgravity. In addition, β-catenin overexpression could also in part attenuate osteoblast differentiation reduction induced by simulated microgravity. Conclusions: The present study is the first to show that r-irisin positively regulates osteoblast differentiation under simulated microgravity through increasing β-catenin expression, which may reveal a novel mechanism, and it provides a prevention strategy for bone loss and muscle atrophy induced by microgravity.

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Section: Discussionmentioning

confidence: 99%

Recombinant Irisin Prevents the Reduction of Osteoblast Differentiation Induced by Stimulated Microgravity through Increasing β-Catenin Expression

Chen

Zhang

Zhao

et al. 2020

IJMS

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“…Apoptosis plays a major role in neurological diseases, including AD, PD, and VaD [22,66,67] . Many signaling pathways regulate apoptosis, including Notch, Bax/Bcl2/caspase3, and IRE1-α/TRAF2/ASK1 pathways [68][69][70] . Among them, Bax/Bcl2/caspase3 signaling has been extensively studied.…”

Section: Discussionmentioning

confidence: 99%

Curcumin Protects Against Cognitive Impairments in a Rat Model of Chronic Cerebral Hypoperfusion Combined with Diabetes Mellitus by Suppressing Neuroinflammation, Apoptosis, and Pyroptosis

Zheng

Zhang

Zhao

et al. 2020

Preprint

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BackgroundChronic cerebral hypoperfusion (CCH) is regarded as a high-risk factor for cognitive decline in vascular dementia (VaD). We have previously shown that diabetes mellitus (DM) synergistically promotes CCH-induced cognitive dysfunction via exacerbating neuroinflammation. Furthermore, curcumin has been shown to exhibit anti-inflammatory and neuroprotective activities. However, the effects of curcumin on CCH-induced cognitive impairments in DM have remained unknown.MethodsRats were fed with a high-fat diet (HFD) and injected with low-dose streptozotocin (STZ), followed by bilateral common carotid artery occlusion (BCCAO), to model DM and CCH in vivo. After BCCAO, curcumin (50 mg/kg) was administered intraperitoneally every two days for eight weeks to evaluate its therapeutic effects. Additionally, mouse BV2 microglial cells were exposed to hypoxia and high glucose to model CCH and DM pathologies in vitro. ResultsCurcumin treatment significantly improved DM/CCH-induced cognitive deficits and attenuated neuronal cell death. Molecular analysis revealed that curcumin exerted protective effects via suppressing neuroinflammation induced by microglial activation, regulating the triggering receptor expressed on myeloid cells 2 (TREM2)/toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway, alleviating apoptosis, and reducing nod-like receptor protein 3 (NLRP3)-dependent pyroptosis.ConclusionsTaken together, our findings suggest that curcumin represents a promising therapy for DM/CCH-induced cognitive impairments.

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“…Studies in human and animal models describe irisin as a potential biomarker, as well as a protective and therapeutic agent in case of cardiac muscle, liver, brain, pancreas, bone, and ovary diseases [6][7][8][9][10][11].…”

Section: Of 11mentioning

confidence: 99%

Circulating Irisin in Healthy Adults: Changes after Acute Exercise, Correlation with Body Composition, and Energy Expenditure Parameters in Cross-Sectional Study

et al. 2020

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Background and Objectives: Skeletal muscles are considered to be the main source of circulating irisin, both at rest and during physical activity. The aim of this study was to investigate the connection between irisin, body composition, and energy metabolism in humans. Materials and Methods: Serum irisin concentrations before and after acute aerobic exercise on a treadmill in 84 healthy adults were measured and their association with body composition and energy expenditure (EE) (obtained from indirect calorimetry) was determined. Results: The total pre-exercise irisin concentrations in males and females were similar, but higher in females when expressed per body mass kg (p < 0.001). There was an association between pre-exercise irisin per body mass kg, visceral fat rating (rho = −0.52, p = 0.001), and lean tissue % (rho = 0.41, p < 0.05) in males and lean body mass index (LBMI) (rho = −0.59, p < 0.001) in females. The pre-exercise irisin concentration correlated with the resting metabolic rate (RMR) in both sexes (rho = 0.44 in males, rho = 0.36 in females; p < 0.05), but with walking, running, and the EE difference from RMR in running (Δ running EE) in males only (rho = 0.32 to 0.37, p < 0.05). There was no significant change in irisin concentration after exercise in 58% of participants, while it decreased in 23%, and increased in 19%. In male subjects with no change in irisin concentration after exercise, running (p < 0.05) and Δ running EE per body mass kg (p < 0.05) were higher than in those with decreased irisin concentration. Conclusions: These findings indicate that the association of irisin concentration with body composition and EE parameters has sex-dependent differences, and acute exercise can lead to various changes in post-exercise irisin levels.

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Neuroprotective effects of irisin against cerebral ischemia/ reperfusion injury via Notch signaling pathway

Cited by 84 publications

References 38 publications

Recombinant Irisin Prevents the Reduction of Osteoblast Differentiation Induced by Stimulated Microgravity through Increasing β-Catenin Expression

Recombinant Irisin Prevents the Reduction of Osteoblast Differentiation Induced by Stimulated Microgravity through Increasing β-Catenin Expression

Curcumin Protects Against Cognitive Impairments in a Rat Model of Chronic Cerebral Hypoperfusion Combined with Diabetes Mellitus by Suppressing Neuroinflammation, Apoptosis, and Pyroptosis

Circulating Irisin in Healthy Adults: Changes after Acute Exercise, Correlation with Body Composition, and Energy Expenditure Parameters in Cross-Sectional Study

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