Sphingomyelin Synthase 2 Promotes Endothelial Dysfunction by Inducing Endoplasmic Reticulum Stress

Hua, Lingyue; Wu, Na; Zhao, Ruilin; He, Xuanhong; Liu, Qian; Li, Xiatian; He, Zhiqiang; Yu, Lushan; Yan, Nianlong

doi:10.3390/ijms20122861

Cited by 15 publications

(21 citation statements)

References 48 publications

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“…The gut microbiota–miRNA interactions are involved in the regulation of epithelial dysfunction, which affects the cardiovascular health of the host. Atherosclerosis is the common pathological basis of a variety of cardiovascular and cerebrovascular diseases, and one of the main pathogenic factors is endothelial dysfunction (Rouyer et al 2019 ; Thijssen et al 2019 ; Hua et al 2019 ). Anthocyanins has been reported to extenuate atherosclerosis and promote cholesterol efflux from macrophages (Xia et al 2006 , 2005 ; Tsuda 2012 ).…”

Section: The Gut Microbiota–mirna Interactions In Cardiovascular Disementioning

confidence: 99%

The roles of the gut microbiota–miRNA interaction in the host pathophysiology

Chen

Wang

2020

Mol Med

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The gut microbiota regulates the biological processes of organisms acting like ‘another’ genome, affecting the health and disease of the host. MicroRNAs, as important physiological regulators, have been found to be involved in health and disease. Recently, the gut microbiota has been reported to affect host health by regulating host miRNAs. For example, Fusobacterium nucleatum could aggravate chemoresistance of colorectal cancer by decreasing the expression of miR-18a* and miR-4802. What’s more, miRNAs can shape the gut microbiota composition, ultimately affecting the host's physiology and disease. miR-515-5p and miR-1226-5p could promote the growth of Fusobacterium nucleatum (Fn) and Escherichia coli (E.coli), which have been reported to drive colorectal cancer. Here, we will review current findings of the interactions between the gut microbiota and microRNAs and discuss how the gut microbiota–microRNA interactions affect host pathophysiology including intestinal, neurological, cardiovascular, and immune health and diseases.

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Section: The Gut Microbiota–mirna Interactions In Cardiovascular Disementioning

confidence: 99%

The roles of the gut microbiota–miRNA interaction in the host pathophysiology

Chen

Wang

2020

Mol Med

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“…For example, in vivo and in vitro studies demonstrate that saturated fatty acids promote ER stress [ 35 ]. Moreover, our previous results verified that cholesterol deposition could cause endothelial dysfunction by activating ER stress [ 36 , 37 ]. In this study, we proved that tunicamycin-induced ER stress elevated both the cholesterol and triglyceride content in Huh7 and THP-1 cells, and LXR-623 reversed these changes.…”

Section: Discussionmentioning

confidence: 61%

Endoplasmic Reticulum Stress Affects Cholesterol Homeostasis by Inhibiting LXRα Expression in Hepatocytes and Macrophages

Zhao

You

et al. 2020

Nutrients

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Atherosclerosis (AS) is the most common cardiovascular disease, and reverse cholesterol transport (RCT) plays an important role in maintaining cholesterol homeostasis. Both endoplasmic reticulum (ER) stress and LXRα can affect the metabolism of cholesterol. However, whether ER stress can modulate cholesterol metabolism by LXRα in hepatocytes and macrophages remains unclear. Therefore, in this study, we aimed to explore the relationship between ER stress induced by tunicamycin and LXRα in hepatocytes and macrophages and clarify their possible mechanisms and roles in AS. C57BL/6 mice and Huh-7 and THP-1 cells were treated with tunicamycin and LXR-623 (an agonist of LXRα) alone or in combination. Tunicamycin-induced ER stress caused liver injury; promoted the accumulation of cholesterol and triglycerides; inhibited the expression of LXRα, ABCA1 and ABCG1 in the livers of mice, thus reducing serum high-density lipoprotein (HDL)-C, low-density lipoprotein (LDL)-C, total cholesterol and triglyceride levels; however, LXR-623 could attenuate ER stress and reverse these changes. We also obtained the same results in Huh-7 and THP-1 cells. ER stress induced by tunicamycin could clearly be reversed by activating LXRα because it promoted cholesterol efflux by enhancing the expression of ABCA1 and ABCG1 in hepatocytes and macrophages, contributing to attenuation of the development of AS.

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“…Moreover, Zhang et al suggested that lipid rafts provide a platform to inhibit the EGFR regulation of MMP-1 in SiHa cells through the MAPK/ERK signaling pathway [ 36 ]. Therefore, the inhibition of SMS2 activity may affect the SM content in lipid rafts and, thus, inhibit transmembrane signal transduction of the Akt signaling pathway in sperm cells [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…The SMS activity of sperm was measured as previously described [ 37 , 41 ]. Briefly, sperm were homogenized in a buffer containing 50mM Tris-HCl, 1mM EDTA, and 5% sucrose.…”

Section: Methodsmentioning

confidence: 99%

Sphingomyelin Synthase 2 Participate in the Regulation of Sperm Motility and Apoptosis

Luo

et al. 2020

Molecules

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Sphingomylin participates in sperm function in animals, and also regulates the Akt and ERK signaling pathways, both of which are associated with the asthenospermia. Sphingomyelin synthase 2 (SMS2) is involved in the biosynthesis of sphingomylin. To determine the relationship between SMS2 and human sperm function, we analyzed the distribution of SMS2 in human sperm and testes, and SMS2 expression in patients with asthenospermia and normozoospermia; human sperm were treated with anti-SMS2, and the sperm motility, penetration ability into methylcellulose, capacitation and acrosome reaction, and sperm [Ca2+]i imaging were evaluated, while the Akt and ERK pathway and cleaved caspase 3 were also analyzed. Results showed that SMS2 was localized in the testis and human sperm, and the protein levels of normozoospermia were higher than asthenospermia. Inhibition of SMS2 activity significantly decreased sperm motility and penetration ability into methylcellulose, but had no influence on capacitation and acrosome reaction, or on intracellular [Ca2+]i compared to IgG-treated control groups. Moreover, the phosphorylation level of Akt was decreased, whereas the phosphorylation of ERK and cleaved-caspase 3 levels were significantly increased. Taken together, SMS2 can affect sperm motility and penetration ability into methylcellulose, and participate in apoptosis associated with the Akt and ERK signaling pathways.

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Sphingomyelin Synthase 2 Promotes Endothelial Dysfunction by Inducing Endoplasmic Reticulum Stress

Cited by 15 publications

References 48 publications

The roles of the gut microbiota–miRNA interaction in the host pathophysiology

The roles of the gut microbiota–miRNA interaction in the host pathophysiology

Endoplasmic Reticulum Stress Affects Cholesterol Homeostasis by Inhibiting LXRα Expression in Hepatocytes and Macrophages

Sphingomyelin Synthase 2 Participate in the Regulation of Sperm Motility and Apoptosis

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