scholarly journals Apolipoprotein M is required for the protective effects of high density lipoprotein against ischemia-induced astrocyte apoptosis

2021 ◽  
Author(s):  
Xiaojia Huang ◽  
Zhiqi Zhai ◽  
Ting Zhou ◽  
Chengju Sheng ◽  
Chao Zhou ◽  
...  
Keyword(s):  
Cell Death ◽  
High Density Lipoprotein ◽  
Apoptotic Cell ◽  
Density Lipoprotein ◽  
Glucose Deprivation ◽  
High Density ◽  
Target Cells ◽  
Protective Effects ◽  
Apolipoprotein M ◽  
Sphingosine 1 Phosphate

Abstract Objectives High density lipoprotein (HDL) has been reported to show protective effects against cell death. Apolipoprotein M (ApoM) in HDL can bind with sphingosine-1-phosphate (S1P) and deliver S1P to target cells. This study aimed to evaluate the effects of HDL on astrocyte apoptosis after ischemic insult and determine the role of ApoM.Methods After ApoM-associated HDL (HDLapoM+) and ApoM-depleted HDL(HDLapoM-) were separated from mouse plasma, primary cultured mouse astrocytes were chellenged with oxygen-glucose deprivation followed by recovery in presence of HDLapoM+ or HDLapoM-. mRNA and protein samples were collected for biochemical analysis.Results The addition of HDLapoM+ attenuated apoptotic cell death in the astrocytes, but HDLapoM- did not show any effect. S1P receptor 1 (S1PR1) expression was upregulated, and specific S1PR1 inhibitor or genetic knockdown of S1pr1 abolished the protective effects. In addition, activation of Akt and ERK was induced by HDLapoM+ or free S1P, and pharmacological inhibition of Akt and ERK reduced the protection of HDLapoM+.Conclusions ApoM is essential for the protective effects of HDL, which depends on S1PR1 activation and downstream activation of Akt/ERK, Thus, ApoM may be a neuroprotective component in plasma.

scholarly journals Apolipoprotein M in High Density Lipoprotein Protects Against Astrocyte Apoptosis Induced By Ischemic Insult Via Sphingosine 1-Phosphate Signaling

2021 ◽  
Author(s):  
Xiaojia Huang ◽  
Zhiqi Zhai ◽  
Ting Zhou ◽  
Chengju Sheng ◽  
Chao Zhou ◽  
...  
Keyword(s):  
Cell Death ◽  
High Density Lipoprotein ◽  
Apoptotic Cell ◽  
Specific Inhibitor ◽  
Density Lipoprotein ◽  
High Density ◽  
Protective Effects ◽  
Ischemic Insult ◽  
Apolipoprotein M ◽  
Sphingosine 1 Phosphate

Abstract Apolipoprotein M (ApoM) has been reported to be contained in high density lipoprotein (HDL) and bound with sphingosine-1-phosphate (S1P). ApoM-associated HDL exerts protective effects against cell death. The aims of the study were to evaluate the effects of ApoM-associated HDL on astrocytes following ischemic insult. Primary cultured mouse astrocytes were treated with oxygen-glucose deprivation (OGD) followed by recovery. The astrocytes underwent apoptosis after treatment with OGD for 4 h and recovery for 24 h. The addition of HDL with ApoM attenuated apoptotic cell death, but HDL without ApoM did not show any effect. Free S1P or ApoM-bound S1P promoted cell survival and inhibited apoptosis. Only S1P receptor 1 (S1PR1) expression was upregulated and blockage of S1PR1 with specific inhibitor or genetic knockdown of S1pr1 abolished the protective effects. In addition, administration of ApoM containing HDL or free S1P induced activation of Akt and Erk in the astrocytes, and pharmacological inhibition of Akt and Erk rescued cell death after OGD treatment. Taken together, ApoM is required for the protective effects of HDL, which depends on delivery of S1P to S1PR1 by ApoM in HDL, indicating ApoM may be a neuroprotective constituent in plasma.

scholarly journals High-density lipoprotein protects cardiomyocytes against necrosis induced by oxygen and glucose deprivation through SR-B1, PI3K, and AKT1 and 2

2018 ◽  
Vol 475 (7) ◽  
pp. 1253-1265 ◽  
Author(s):  
Kristina K. Durham ◽  
Kevin M. Chathely ◽  
Bernardo L. Trigatti
Keyword(s):  
Cell Death ◽  
High Density Lipoprotein ◽  
Ischemia Reperfusion ◽  
Density Lipoprotein ◽  
Glucose Deprivation ◽  
High Density ◽  
Dependent Manner ◽  
Protective Effects ◽  
Oxygen And Glucose Deprivation ◽  
Ventricular Cardiomyocytes

The cardioprotective lipoprotein HDL (high-density lipoprotein) prevents myocardial infarction and cardiomyocyte death due to ischemia/reperfusion injury. The scavenger receptor class B, type 1 (SR-B1) is a high-affinity HDL receptor and has been shown to mediate HDL-dependent lipid transport as well as signaling in a variety of different cell types. The contribution of SR-B1 in cardiomyocytes to the protective effects of HDL on cardiomyocyte survival following ischemia has not yet been studied. Here, we use a model of simulated ischemia (oxygen and glucose deprivation, OGD) to assess the mechanistic involvement of SR-B1, PI3K (phosphatidylinositol-3-kinase), and AKT in HDL-mediated protection of cardiomyocytes from cell death. Neonatal mouse cardiomyocytes and immortalized human ventricular cardiomyocytes, subjected to OGD for 4 h, underwent substantial cell death due to necrosis but not necroptosis or apoptosis. Pretreatment of cells with HDL, but not low-density lipoprotein, protected them against OGD-induced necrosis. HDL-mediated protection was lost in cardiomyocytes from SR-B1−/− mice or when SR-B1 was knocked down in human immortalized ventricular cardiomyocytes. HDL treatment induced the phosphorylation of AKT in cardiomyocytes in an SR-B1-dependent manner. Finally, chemical inhibition of PI3K or AKT or silencing of either AKT1 or AKT2 gene expression abolished HDL-mediated protection against OGD-induced necrosis of cardiomyocytes. These results are the first to identify a role of SR-B1 in mediating the protective effects of HDL against necrosis in cardiomyocytes, and to identify AKT activation downstream of SR-B1 in cardiomyocytes.

scholarly journals Overexpression of Transcripts Coding for Renin-b but Not for Renin-a Reduce Oxidative Stress and Increase Cardiomyoblast Survival under Starvation Conditions

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1204
Author(s):  
Heike Wanka ◽  
Philipp Lutze ◽  
Alexander Albers ◽  
Janine Golchert ◽  
Doreen Staar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
B Cells ◽  
Apoptotic Cell ◽  
Renin Angiotensin System ◽  
Glucose Deprivation ◽  
Protective Effects ◽  
Glucose Depletion ◽  
A Cells ◽  
Apoptosis And Necrosis

A stimulated renin-angiotensin system is known to promote oxidative stress, apoptosis, necrosis and fibrosis. Renin transcripts (renin-b; renin-c) encoding a cytosolic renin isoform have been discovered that may in contrast to the commonly known secretory renin (renin-a) exert protective effects Here, we analyzed the effect of renin-a and renin-b overexpression in H9c2 cardiomyoblasts on apoptosis and necrosis as well as on potential mechanisms involved in cell death processes. To mimic ischemic conditions, cells were exposed to glucose starvation, anoxia or combined oxygen–glucose deprivation (OGD) for 24 h. Under OGD, control cells exhibited markedly increased necrotic and apoptotic cell death accompanied by enhanced ROS accumulation, loss of mitochondrial membrane potential and decreased ATP levels. The effects of OGD on necrosis were exaggerated in renin-a cells, but markedly diminished in renin-b cells. However, with respect to apoptosis, the effects of OGD were almost completely abolished in renin-b cells but interestingly also moderately diminished in renin-a cells. Under glucose depletion we found opposing responses between renin-a and renin-b cells; while the rate of necrosis and apoptosis was aggravated in renin-a cells, it was attenuated in renin-b cells. Based on our results, strategies targeting the regulation of cytosolic renin-b as well as the identification of pathways involved in the protective effects of renin-b may be helpful to improve the treatment of ischemia-relevant diseases.

High-density lipoprotein-associated sphingosine-1-phosphate activity in heterozygous familial hypercholesterolaemia

2016 ◽  
Vol 47 (1) ◽  
pp. 38-43 ◽  
Author(s):  
Miguel A. Frias ◽  
Aurélien Thomas ◽  
Marie-Claude Brulhart-Meynet ◽  
Oskar Kövamees ◽  
John Pernow ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Familial Hypercholesterolaemia ◽  
Density Lipoprotein ◽  
High Density ◽  
Sphingosine 1 Phosphate ◽  
Heterozygous Familial Hypercholesterolaemia

scholarly journals Does high-density lipoprotein protect vascular function in healthy pregnancy?

2016 ◽  
Vol 130 (7) ◽  
pp. 491-497 ◽  
Author(s):  
Wan N. Wan Sulaiman ◽  
Muriel J. Caslake ◽  
Christian Delles ◽  
Helen Karlsson ◽  
Monique T. Mulder ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Density Lipoprotein ◽  
Vascular Endothelium ◽  
Vascular Function ◽  
Cell Damage ◽  
Density Lipoprotein ◽  
High Density ◽  
Major Protein ◽  
Protective Effects ◽  
In Pregnancy

The maternal adaptation to pregnancy includes hyperlipidaemia, oxidative stress and chronic inflammation. In non-pregnant individuals, these processes are usually associated with poor vascular function. However, maternal vascular function is enhanced in pregnancy. It is not understood how this is achieved in the face of the adverse metabolic and inflammatory environment. Research into cardiovascular disease demonstrates that plasma HDL (high-density lipoprotein), by merit of its functionality rather than its plasma concentration, exerts protective effects on the vascular endothelium. HDL has vasodilatory, antioxidant, anti-thrombotic and anti-inflammatory effects, and can protect against endothelial cell damage. In pregnancy, the plasma HDL concentration starts to rise at 10 weeks of gestation, peaking at 20 weeks. The initial rise in plasma HDL occurs around the time of the establishment of the feto-placental circulation, a time when the trophoblast plugs in the maternal spiral arteries are released, generating oxidative stress. Thus there is the intriguing possibility that new HDL of improved function is synthesized around the time of the establishment of the feto-placental circulation. In obese pregnancy and, to a greater extent, in pre-eclampsia, plasma HDL levels are significantly decreased and maternal vascular function is reduced. Wire myography studies have shown an association between the plasma content of apolipoprotein AI, the major protein constituent of HDL, and blood vessel relaxation. These observations lead us to hypothesize that HDL concentration, and function, increases in pregnancy in order to protect the maternal vascular endothelium and that in pre-eclampsia this fails to occur.

scholarly journals Effects of Myeloperoxidase-Induced Oxidation on Antiatherogenic Functions of High-Density Lipoprotein

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Takahiro Kameda ◽  
Ryunosuke Ohkawa ◽  
Kouji Yano ◽  
Yoko Usami ◽  
Akari Miyazaki ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Umbilical Vein ◽  
Functional Characterization ◽  
Density Lipoprotein ◽  
High Density ◽  
Ldl Oxidation ◽  
Protective Effects ◽  
Antioxidant Ability ◽  
Monocyte Migration ◽  
Anti Inflammatory

High-density lipoprotein (HDL) has protective effects against the development of atherosclerosis; these effects include reverse cholesterol transport, antioxidant ability, and anti-inflammation. Myeloperoxidase (MPO) secreted by macrophages in atherosclerotic lesions generates tyrosyl radicals in apolipoprotein A-I (apoA-I) molecules, inducing the formation of apoA-I/apoA-II heterodimers through the tyrosine-tyrosine bond in HDL. Functional characterization of HDL oxidized by MPO could provide useful information about the significance of apoA-I/apoA-II heterodimers measurement. We investigated the effects of MPO-induced oxidation on the antiatherogenic functions of HDL as described above. The antioxidant ability of HDL, estimated as the effect on LDL oxidation induced by copper sulfate, was not significantly affected after MPO oxidation. HDL reduced THP-1 monocyte migration by suppressing the stimulation of human umbilical vein endothelial cells induced by lipopolysaccharide (LPS). MPO-oxidized HDL also showed inhibition of THP-1 chemotaxis, but the extent of inhibition was significantly attenuated compared to intact HDL. MPO treatment did not affect the cholesterol efflux capacity of HDL from [3H]-cholesterol-laden macrophages derived from THP-1 cells. The principal effect of MPO oxidation on the antiatherogenic potential of HDL would be the reduction of anti-inflammatory ability, suggesting that measurement of apoA-I/apoA-II heterodimers might be useful to estimate anti-inflammatory ability of HDL.

Newly developed reconstituted high-density lipoprotein containing sphingosine-1-phosphate induces endothelial tube formation

2007 ◽  
Vol 194 (1) ◽  
pp. 159-168 ◽  
Author(s):  
Yoshino Matsuo ◽  
Shin-ichiro Miura ◽  
Akira Kawamura ◽  
Yoshinari Uehara ◽  
Kerry-Anne Rye ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
Tube Formation ◽  
High Density ◽  
Endothelial Tube Formation ◽  
Sphingosine 1 Phosphate
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