Active form of vitamin D analogue mitigates neurodegenerative changes in Alzheimer’s disease in rats by targeting Keap1/Nrf2 and MAPK-38p/ERK signaling pathways

El-Din, Shimaa Saad; Rashed, Laila Ahmed; Medhat, Engy; Aboulhoda, Basma Emad; Badawy, Ahmed; ShamsEldeen, Asmaa Mohammed; Abdelgwad, Marwa

doi:10.1016/j.steroids.2020.108586

Cited by 52 publications

(29 citation statements)

References 42 publications

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“…Vitamin D may have a possible beneficial influence on this signal transduction pathway and its effects, however few studies investigate the link between them. In an Alzheimer’s disease rat model, vitamin D analogue treatment significantly increased the Nrf2 expression and significantly decreased a lipid peroxidation marker, the malondialdehyde (MDA) levels compared to non-treated group [ 35 ]. There is one study that hypothesizes that lithocholic acid can bind to VDR, and VDR activates SIRT1/Nrf2 signal pathway and results in beneficial effects of lithocholic acid on injured intestinal barrier function [ 36 ].…”

Section: Discussion Limitations and Strengthsmentioning

confidence: 99%

Vitamin D Deficiency Induces Elevated Oxidative and Biomechanical Damage in Coronary Arterioles in Male Rats

et al. 2020

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Background: Several reports prove interconnection between vitamin D (VD) deficiency and increased cardiovascular risk. Our aim was to investigate the effects of VD status on biomechanical and oxidative–nitrative (O–N) stress parameters of coronary arterioles in rats. Methods: 4-week-old male Wistar rats were divided into a control group (11 animals) with optimal VD supply (300 IU/kgbw/day) and a VD-deficient group (11 animals, <5 IU/kg/day). After 8 weeks, coronary arteriole segments were prepared. Geometrical, elastic, and biomechanical characteristics were measured by in vitro arteriography. O–N stress markers were investigated by immunohistochemistry. Results: Inner radius decreased; wall thickness and wall-thickness/lumen diameter ratio increased; tangential wall stress and elastic modulus were reduced in VD-deficient group. No difference could be found in wall-cross-sectional area, intima-media area %. While the elastic elements of the vessel wall decreased, the α-smooth muscle actin (α-SMA) immunostaining intensity showed no changes. Significant elevation was found in the lipid peroxidation marker of 4-hidroxy-2-nonenal (HNE), while other O–N stress markers staining intensity (poly(ADP)ribose, 3-nitrotyrosine) did not change. Conclusions: Inward eutrophic remodeling has developed. The potential background of these impairments may involve the initial change in oxidative damage markers (HNE). These mechanisms can contribute to the increased incidence of the cardiovascular diseases in VD deficiency.

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Section: Discussion Limitations and Strengthsmentioning

confidence: 99%

Vitamin D Deficiency Induces Elevated Oxidative and Biomechanical Damage in Coronary Arterioles in Male Rats

et al. 2020

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“…El-Din et al demonstrated that Nrf2 and its downstream anti-oxidant effectors were decreased in AD rats, while the neuro-inflammation as evidenced by TNF-α and phosphorylated ERK1/2 that led to the hyperphosphorylation of tau protein were increased (Fig. 2) [71]. Maxacalcitol, a vitamin D analogue, significantly improved cognitive impairment of AD rats via elevating Nrf2 signaling pathway as well as reducing the hyperphosphorylation of ERK1/2 and tau proteins [71], making AD more curable than inevitable (Fig.…”

Section: Vitamin Metabolismmentioning

confidence: 96%

“…2) [71]. Maxacalcitol, a vitamin D analogue, significantly improved cognitive impairment of AD rats via elevating Nrf2 signaling pathway as well as reducing the hyperphosphorylation of ERK1/2 and tau proteins [71], making AD more curable than inevitable (Fig. 2).…”

Section: Vitamin Metabolismmentioning

confidence: 98%

Redox signaling and Alzheimer’s disease: from pathomechanism insights to biomarker discovery and therapy strategy

Chen

Wang²,

Wang

et al. 2020

Biomark Res

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Aging and average life expectancy have been increasing at a rapid rate, while there is an exponential risk to suffer from brain-related frailties and neurodegenerative diseases as the population ages. Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide with a projected expectation to blossom into the major challenge in elders and the cases are forecasted to increase about 3-fold in the next 40 years. Considering the etiological factors of AD are too complex to be completely understood, there is almost no effective cure to date, suggesting deeper pathomechanism insights are urgently needed. Metabolites are able to reflect the dynamic processes that are in progress or have happened, and metabolomic may therefore provide a more cost-effective and productive route to disease intervention, especially in the arena for pathomechanism exploration and new biomarker identification. In this review, we primarily focused on how redox signaling was involved in AD-related pathologies and the association between redox signaling and altered metabolic pathways. Moreover, we also expatiated the main redox signaling-associated mechanisms and their cross-talk that may be amenable to mechanism-based therapies. Five natural products with promising efficacy on AD inhibition and the benefit of AD intervention on its complications were highlighted as well. Graphical Abstract

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“…It has been reported that VitD inhibits MAPK signalling pathway activation [16]. The MAPK signalling pathway participates in the physiological functions of various cancer cells in vivo, including proliferation, apoptosis and differentiation [17].…”

Section: Vitd Inhibited the Mapk Signalling Pathway Of Oscc By Inhibimentioning

confidence: 99%

Vitamin D inhibits the proliferation of Oral Squamous Cell Carcinoma by suppressing lncRNA LUCAT1 through the MAPK pathway

et al. 2020

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Background: Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer worldwide. Recent studies have suggested that vitamin D (VitD) is associated with a reduced risk of many chronic illnesses, including cancer. However, the role of vitamin D in OSCC has rarely been reported. Materials and Methods: The effect of vitamin D and control treatment were examined by cell clone formation assay. Using RNA-seq, we globally identified VitD-regulated long noncoding RNAs (lncRNAs). The expression of LUCAT1 in OSCC tissues and cell lines was examined by qRT-PCR. The correlation between LUCAT1 expression level and clinicopathological characteristics was analyzed. The biological roles of LUCAT1 in OSCC cell proliferation was determined by CCK8 and cell colony formation. The role of LUCAT1 in OSCC growth was further confirmed by mouse xenograft tumor model. Combined with the literature, the mechanism of action of LUICAT1 was verified by western blot. Results: In this study, we observed that VitD inhibited tumour cell growth in OSCC. We found that lncRNA LUCAT1 was downregulated by VitD and served as an important mediator of VitD in inhibiting OSCC cell proliferation. Moreover, we observed that the expression of LUCAT1 was significantly upregulated in OSCC tissues compared to non-tumour tissues. We further demonstrated that LUCAT1 promoted the proliferation of oral cancer cells by enhancing the activation of the mitogen protein kinase (MAPK) signalling pathway. Conclusion: In summary, our results show that VitD inhibited the growth of OSCC cells through the LUCAT1-MAPK signalling pathway. Our study suggested that VitD could suppress the progression of oral cancer, and LUCAT1 may be a potential tumour marker for the diagnosis and prognosis of OSCC.

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Active form of vitamin D analogue mitigates neurodegenerative changes in Alzheimer’s disease in rats by targeting Keap1/Nrf2 and MAPK-38p/ERK signaling pathways

Cited by 52 publications

References 42 publications

Vitamin D Deficiency Induces Elevated Oxidative and Biomechanical Damage in Coronary Arterioles in Male Rats

Vitamin D Deficiency Induces Elevated Oxidative and Biomechanical Damage in Coronary Arterioles in Male Rats

Redox signaling and Alzheimer’s disease: from pathomechanism insights to biomarker discovery and therapy strategy

Vitamin D inhibits the proliferation of Oral Squamous Cell Carcinoma by suppressing lncRNA LUCAT1 through the MAPK pathway

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