Apolipoprotein M Protects Lipopolysaccharide-Treated Mice from Death and Organ Injury

Kurano, Makoto; Tsuneyama, Koichi; Morimoto, Yuki; Shimizu, Tomo; Jona, Masahiro; Kassai, Hidetoshi; Nakao, Kazuki; Aiba, Atsu; Yatomi, Yutaka

doi:10.1055/s-0038-1641750

Cited by 49 publications

(38 citation statements)

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“…The ApoM KO mice were produced as described in the previous report [ 17 ], and the blood samples were collected from 10-week-old male KO mice and WT mice, which were subjected to a 6-h fast. The plasma samples were separated into HDL and Lp-dep fractions, and the S1P and DH-S1P levels were measured.…”

Section: Methodsmentioning

confidence: 99%

Dihydro-sphingosine 1-phosphate interacts with carrier proteins in a manner distinct from that of sphingosine 1-phosphate

et al. 2018

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Dihydro-sphingosine 1-phosphate (DH-S1P) is an analog of sphingosine 1-phosphate (S1P), which is a potent lysophospholipid mediator. DH-S1P has been proposed to exert physiological properties similar to S1P. Although S1P is known to be carried on HDL via apolipoprotein M (apoM), the association between DH-S1P and HDL/apoM has not been fully elucidated. Therefore, in the present study, we aimed to elucidate this association and to compare it with that of S1P and HDL/apoM. First, we investigated the distributions of S1P and DH-S1P among lipoproteins and lipoprotein-depleted fractions in human serum and plasma samples and observed that both S1P and DH-S1P were detected on HDL; furthermore, elevated amounts of DH-S1P in serum samples were distributed to the lipoprotein-depleted fraction to a greater degree than to the HDL fraction. Concordantly, a preference for HDL over albumin was only observed for S1P, and not for DH-S1P, when the molecules were secreted from platelets. Regarding the association with HDL, although both S1P and DH-S1P prefer to bind to HDL, HDL preferentially accepts S1P over DH-S1P. For the association with apoM, S1P was not detected on HDL obtained from apoM knockout mice, while DH-S1P was detected. Moreover, apoM retarded the degradation of S1P, but not of DH-S1P. These results suggest that S1P binds to HDL via apoM, while DH-S1P binds to HDL in a non-specific manner. Thus, DH-S1P is not a mere analog of S1P and might possess unique clinical significance.

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Section: Methodsmentioning

confidence: 99%

Dihydro-sphingosine 1-phosphate interacts with carrier proteins in a manner distinct from that of sphingosine 1-phosphate

et al. 2018

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“…Since 2011, when ApoM was first ABBREVIATIONS: ApoM, apolipoprotein M; BW, body weight; Col, collagen; Ctgf, connective tissue growth factor; FBS, fetal bovine serum; Fn, fibronectin; GFP, green fluorescent protein; HIGA, hyper-IgA; KO, knockout; PAS, periodic acid-Schiff; PTX, pertussis toxin; rApoM, recombinant ApoM; S1P, sphingosine 1-phosphate; siApoM, small interfering RNA against murine ApoM; siCtl, control siRNA; WT, wild type established as a carrier of S1P (25), we and others have demonstrated that ApoM is not actually a carrier of S1P, but rather is a modulator of S1P metabolism, and S1P bound to albumin is unstable in plasma, whereas S1P bound to ApoM is stable (30)(31)(32). We were able to modulate the plasma S1P levels continuously using the adenoviral gene transfer of ApoM or the knockdown of ApoM in an in vivo siRNA system (33,34). The epidemiologic association between HDL and the progression of chronic kidney diseases also prompted us to investigate the association between S1P and IgA nephropathy (35,36).…”

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confidence: 89%

“…For the experiments investigating cell proliferation, MES13 cells were cultured on a 96‐well plate at a concentration of 2000 cells/well overnight. The medium was replaced with an FBS‐free medium containing the vehicle or 10 µM VPC, 10 µM JTE, or pertussis toxin (PTX, P7208; MilliporeSigma) at 20 ng/ml for 2 h. Then, the medium was replaced with an FBS‐free medium containing pharmacological inhibitors with various concentrations of S1P bound to 0.004% w/w fatty acid‐free albumin or recombinant ApoM (rApoM; R&D Systems, Minneapolis, MN, USA) or with HDL collected from 10‐wk‐old wild‐type C57BL/6 (WT) mice or ApoM‐knockout C57BL/6 (KO) mice, described in a previous paper (34), at a concentration of 0.25 mg protein/ml. In detail, we prepared S1P bound to albumin or recombinant ApoM as follows; S1P (Enzo Life Sciences, Plymouth Meeting, PA, USA) was dissolved in methanol.…”

Section: Histologic Analysismentioning

confidence: 99%

“…Since 2011, when ApoM was first established as a carrier of S1P (25), we and others have demonstrated that ApoM is not actually a carrier of S1P, but rather is a modulator of S1P metabolism, and S1P bound to albumin is unstable in plasma, whereas S1P bound to ApoM is stable (30–32). We were able to modulate the plasma S1P levels continuously using the adenoviral gene transfer of ApoM or the knockdown of ApoM in an in vivo siRNA system (33, 34). The epidemiologic association between HDL and the progression of chronic kidney diseases also prompted us to investigate the association between S1P and IgA nephropathy (35, 36).…”

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Apolipoprotein M suppresses the phenotypes of IgA nephropathy in hyper‐IgA mice

et al. 2019

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Because the association between sphingosine 1‐phosphate (S1P)/apolipoprotein M (ApoM) and chronic kidney diseases has not been established, we investigated the involvement of S1P/ApoM in the phenotypes of IgA nephropathy in hyper‐IgA (HIGA) mice. The overexpression of ApoM in adenoviral gene transfer ameliorated the phenotypes of IgA nephropathy in HIGA mice, whereas the knockdown of ApoM with siRNA caused deterioration. When ApoM‐overexpressing HIGA mice were treated with VPC23019, an antagonist against S1P receptor 1 (S1P1) and 3 (S1P3), we observed that the protective effects of ApoM were reversed, whereas JTE013, an antagonist against S1P2, did not inhibit the effects. We also found that S1P bound to albumin accelerated the proliferation of MES13 cells and the fibrotic changes of HK2 cells, which were inhibited by JTE013, whereas S1P bound to ApoM suppressed these changes, which were inhibited by VPC23019. These results suggest that S1P bound to ApoM possesses properties protective against the phenotypes of IgA nephropathy through S1P1 and S1P3, whereas S1P bound to albumin exerts deteriorating effects through S1P2. ApoM may be useful as a therapeutic target to treat or retard the progression of IgA nephropathy.—Kurano, M., Tsuneyama, K., Morimoto, Y., Nishikawa, M., Yatomi, Y. Apolipoprotein M suppresses the phenotypes of IgA nephropathy in hyper‐IgA mice. FASEB J. 33, 5181–5195 (2019). http://www.fasebj.org

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“…Apolipoprotein M is a 25-kDa protein contained in about 5% of HDL particles that can bind sphingosine 1-phosphate (S1P, see below), whose concentration is drastically decreased in sepsis and inflammatory conditions [29]. Apolipoprotein M (ApoM) was shown to limit LPS-induced acute lung injury [30], as well as mortality in LPS-treated mice [31].…”

Section: Hdl Proteomementioning

confidence: 99%

High-Density Lipoproteins Are Bug Scavengers

2020

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Lipoproteins were initially defined according to their composition (lipids and proteins) and classified according to their density (from very low- to high-density lipoproteins—HDLs). Whereas their capacity to transport hydrophobic lipids in a hydrophilic environment (plasma) is not questionable, their primitive function of cholesterol transporter could be challenged. All lipoproteins are reported to bind and potentially neutralize bacterial lipopolysaccharides (LPS); this is particularly true for HDL particles. In addition, HDL levels are drastically decreased under infectious conditions such as sepsis, suggesting a potential role in the clearance of bacterial material and, particularly, LPS. Moreover, "omics" technologies have unveiled significant changes in HDL composition in different inflammatory states, ranging from acute inflammation occurring during septic shock to low-grade inflammation associated with moderate endotoxemia such as periodontal disease or obesity. In this review, we will discuss HDL modifications associated with exposure to pathogens including bacteria, viruses and parasites, with a special focus on sepsis and the potential of HDL therapy in this context. Low-grade inflammation associated with atherosclerosis, periodontitis or metabolic syndrome may also highlight the protective role of HDLs in theses pathologies by other mechanisms than the reverse transport of cholesterol.

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Apolipoprotein M Protects Lipopolysaccharide-Treated Mice from Death and Organ Injury

Abstract: These results suggest that apoM possesses protective properties against LPS-induced organ injuries and could potentially be introduced as a novel therapy for the severe conditions that are consequent to sepsis.

Cited by 49 publications

References 50 publications

Dihydro-sphingosine 1-phosphate interacts with carrier proteins in a manner distinct from that of sphingosine 1-phosphate

Dihydro-sphingosine 1-phosphate interacts with carrier proteins in a manner distinct from that of sphingosine 1-phosphate

Apolipoprotein M suppresses the phenotypes of IgA nephropathy in hyper‐IgA mice

High-Density Lipoproteins Are Bug Scavengers

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