Correlation between angiotensin 1–7-mediated Mas receptor expression with motor improvement, activated STAT3/SOCS3 cascade, and suppressed HMGB-1/RAGE/NF-κB signaling in 6-hydroxydopamine hemiparkinsonian rats

Rabie, Mostafa A.; Fattah, Mai A. Abd El; Nassar, Noha N.; Abdallah, Dalaal M.; El‐Abhar, Hanan S.

doi:10.1016/j.bcp.2019.113681

Cited by 23 publications

(20 citation statements)

References 59 publications

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“…Stimulation of ACE2/Ang(1–7)/MasR axis by DIZE also ameliorates the behavioral deficits and protects the brain against amyloid pathology, inflammatory overactivation, and oxidative damage in animal models of Alzheimer's disease (Evans et al, 2020 ; Kamel et al, 2018 ). Additionally, direct intrastriatal administration of Ang(1–7) can reduce brain lesions and motor deficits in 6‐hydroxydopamine‐induced hemiparkinsonian rats (Rabie et al, 2020 ). These results all lend weight to the potential beneficial effects of ACE2/Ang(1–7)/MasR axis in the neurodegenerative disorders that are repeatedly demonstrated to be characterized by sustained inflammation and excessive oxidative damage.…”

Section: Discussionmentioning

confidence: 99%

Activation of angiotensin‐converting enzyme 2/angiotensin (1–7)/mas receptor axis triggers autophagy and suppresses microglia proinflammatory polarization via forkhead box class O1 signaling

et al. 2021

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Brain renin‐angiotensin (Ang) system (RAS) is implicated in neuroinflammation, a major characteristic of aging process. Angiotensin (Ang) II, produced by angiotensin‐converting enzyme (ACE), activates immune system via angiotensin type 1 receptor (AT1), whereas Ang(1–7), generated by ACE2, binds with Mas receptor (MasR) to restrain excessive inflammatory response. Therefore, the present study aims to explore the relationship between RAS and neuroinflammation. We found that repeated lipopolysaccharide (LPS) treatment shifted the balance between ACE/Ang II/AT1 and ACE2/Ang(1–7)/MasR axis to the deleterious side and treatment with either MasR agonist, AVE0991 (AVE) or ACE2 activator, diminazene aceturate, exhibited strong neuroprotective actions. Mechanically, activation of ACE2/Ang(1–7)/MasR axis triggered the Forkhead box class O1 (FOXO1)‐autophagy pathway and induced superoxide dismutase (SOD) and catalase (CAT), the FOXO1‐targeted antioxidant enzymes. Meanwhile, knockdown of MasR or FOXO1 in BV2 cells, or using the selective FOXO1 inhibitor, AS1842856, in animals, suppressed FOXO1 translocation and compromised the autophagic process induced by MasR activation. We further used chloroquine (CQ) to block autophagy and showed that suppressing either FOXO1 or autophagy abrogated the anti‐inflammatory action of AVE. Likewise, Ang(1–7) also induced FOXO1 signaling and autophagic flux following LPS treatment in BV2 cells. Cotreatment with AS1842856 or CQ all led to autophagic inhibition and thereby abolished Ang(1–7)‐induced remission on NLRP3 inflammasome activation caused by LPS exposure, shifting the microglial polarization from M1 to M2 phenotype. Collectively, these results firstly illustrated the mechanism of ACE2/Ang(1–7)/MasR axis in neuroinflammation, strongly indicating the involvement of FOXO1‐mediated autophagy in the neuroimmune‐modulating effects triggered by MasR activation.

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Section: Discussionmentioning

confidence: 99%

Activation of angiotensin‐converting enzyme 2/angiotensin (1–7)/mas receptor axis triggers autophagy and suppresses microglia proinflammatory polarization via forkhead box class O1 signaling

et al. 2021

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“…In accordance with our findings, previous studies indicated that anticancer agents inhibited tumor growth, induced autophagy, and suppressed the JAK2/STAT3 pathway, while the autophagy inhibitor CQ enhanced this effect [42][43][44][45]; however, the mechanisms remain unclear, because the RAGE and STAT3 pathways are also regulated by various factors, including HMGB1, NF-κB, fibroblast-specific protein 1 (FSP1), SOCS3, CXCR3, etc. [46][47][48][49][50]. This could partially explain how PT combined with CQ might affect a complicated network in cells when regulating the RAGE and STAT3 pathways.…”

Section: Discussionmentioning

confidence: 99%

Chloroquine Potentiates the Anticancer Effect of Pterostilbene on Pancreatic Cancer by Inhibiting Autophagy and Downregulating the RAGE/STAT3 Pathway

et al. 2021

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The treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, because pro-survival signaling pathways—such as the receptor for advanced glycation end products (RAGE)/signal transducer and activator of transcription 3 (STAT3) pathway—are overexpressed in PDAC cells. Moreover, PDAC cells are highly resistant to chemotherapeutic agents because of autophagy induction. Therefore, autophagy and its modulated signaling pathways are attractive targets for developing novel therapeutic strategies for PDAC. Pterostilbene is a stilbenoid chemically related to resveratrol, and has potential for the treatment of cancers. Accordingly, we investigated whether the autophagy inhibitor chloroquine could potentiate the anticancer effect of pterostilbene in the PDAC cell lines MIA PaCa-2 and BxPC-3, as well as in an orthotopic animal model. The results indicated that pterostilbene combined with chloroquine significantly inhibited autophagy, decreased cell viability, and sensitized the cells to pterostilbene-induced apoptosis via downregulation of the RAGE/STAT3 and protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways in PDAC cells. The results of the orthotopic animal model showed that pterostilbene combined with chloroquine significantly inhibited pancreatic cancer growth, delayed tumor quadrupling times, and inhibited autophagy and STAT3 in pancreatic tumors. In summary, the present study suggested the novel therapeutic strategy of pterostilbene combined with chloroquine against the growth of pancreatic ductal adenocarcinoma by inhibiting autophagy and downregulating the RAGE/STAT3 signaling pathways.

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“…Alarmins are possible danger signals associated with COVID-19 and comorbidities [63], and S100A8/A9, high mobility group box 1 (HMGB1), and histones are considered potential therapeutic targets [64][65][66]. The elevation of S100A8/A9 and HMGB1 by Ang-II suggests the involvement of alarmins in unbalanced RAS [67,68], and the ACE2/Ang-(1-7)/MasR axis could suppress HMGB1 signaling [69]. Although there is no application of alarmin blockade in COVID-19 and comorbidities, previous studies have suggested the therapeutic potential of neutralizing antibodies against S100A8/A9, HMGB1, or histones for the inhibition of pulmonary fibrosis and sepsis-associated ALI/ARDS [70][71][72][73].…”

Section: Risk Factors and Potential Mechanisms Of Severity And Mortality Of Covid-19mentioning

confidence: 99%

Sunlight Exposure and Phototherapy: Perspectives for Healthy Aging in an Era of COVID-19

Nakano

Chiang

Chen

et al. 2021

IJERPH

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Most humans depend on sunlight exposure to satisfy their requirements for vitamin D3. However, the destruction of the ozone layer in the past few decades has increased the risk of skin aging and wrinkling caused by excessive exposure to ultraviolet (UV) radiation, which may also promote the risk of skin cancer development. The promotion of public health recommendations to avoid sunlight exposure would reduce the risk of skin cancer, but it would also enhance the risk of vitamin D3 insufficiency/deficiency, which may cause disease development and progression. In addition, the ongoing global COVID-19 pandemic may further reduce sunlight exposure due to stay-at-home policies, resulting in difficulty in active and healthy aging. In this review article, we performed a literature search in PubMed and provided an overview of basic and clinical data regarding the impact of sunlight exposure and vitamin D3 on public health. We also discuss the potential mechanisms and clinical value of phototherapy with a full-spectrum light (notably blue, red, and near-infrared light) as an alternative to sunlight exposure, which may contribute to combating COVID-19 and promoting active and healthy aging in current aged/superaged societies.

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Correlation between angiotensin 1–7-mediated Mas receptor expression with motor improvement, activated STAT3/SOCS3 cascade, and suppressed HMGB-1/RAGE/NF-κB signaling in 6-hydroxydopamine hemiparkinsonian rats

Cited by 23 publications

References 59 publications

Activation of angiotensin‐converting enzyme 2/angiotensin (1–7)/mas receptor axis triggers autophagy and suppresses microglia proinflammatory polarization via forkhead box class O1 signaling

Activation of angiotensin‐converting enzyme 2/angiotensin (1–7)/mas receptor axis triggers autophagy and suppresses microglia proinflammatory polarization via forkhead box class O1 signaling

Chloroquine Potentiates the Anticancer Effect of Pterostilbene on Pancreatic Cancer by Inhibiting Autophagy and Downregulating the RAGE/STAT3 Pathway

Sunlight Exposure and Phototherapy: Perspectives for Healthy Aging in an Era of COVID-19

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