Mg<sup>2+</sup> modulates membrane sphingolipid and lipid second messenger levels in vascular smooth muscle cells

Morrill, Gene A.; Gupta, Raj K.; Kostellow, Adele B.; Ma, Gui-Ying; Zhang, Amin; Altura, Bella T.; Altura, Burton M.

doi:10.1016/s0014-5793(98)01446-x

Cited by 52 publications

(64 citation statements)

References 25 publications

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“…Our experiments confirm and add further support to the concept that lowered levels of Mg can lead to the formation of ceramide in cardiovascular tissues and cells (55). We also confirm that ceramide synthesis in cardiovascular tissues and cells is, at least, in part, a result of activation of CS and N-SMase (14 -16, 55).…”

Section: H324supporting

confidence: 85%

“…Rat aortic VSMCs were isolated according to established methods (13,81) in our laboratory (n ϭ 10 -12 animals/group) and cultured in DMEM containing 1.2 mmol/l [Mg 2ϩ ]o, FCS, and antibiotics at 37°C in a humidified atmosphere composed of 95% air-5% CO2 (55,81). After confluence had been reached, VSMCs were placed in media containing either 0.3, 0.6, or 1.2 mmol/l [Mg 2ϩ ]o for varying periods of time (2 or 24 h).…”

Section: Methodsmentioning

confidence: 99%

“…11). ]o with or without 75 uM scyphostatin (SigmaAldrich) for 18 h. We extracted the lipids in the cells as we have detailed elsewhere (54,55). The ceramide was next converted into ceramide-1-[ 32 P]phosphate by Escherichia coli DAG kinase, and the lipids were separated on high-performance TLC plates as described elsewhere (16,58).…”

Section: Influence Of An Inhibitor (Fumonisin B1) Of Cs On the De Novomentioning

confidence: 99%

“…As early as 15 years ago, using cerebral and peripheral vascular smooth muscle cells (VSMCs) in primary cultures, it was demonstrated that variation in free extracellular Mg 2ϩ concentration ([Mg 2ϩ ] o ) causes sustained alterations in membrane phospholipids and second messengers as well as activation of several signal transcription molecules, identical to those mentioned above (13,54,55). Such paradigms, using variations in Mg 2ϩ , also cause membrane oxidation, truncation of membrane fatty acids, and the activation of apoptotic pathways (i.e., caspase-3, apoptotic protease activation factor-1, and release of mitochondrial cytochrome c) concomitant with the significant activation of neutral sphingomyelinase (N-SMase) and alterations in membrane sphingomyelin (SM), leading to the release of ceramides in cultured VSMCs (14 -16, 68).…”

mentioning

confidence: 93%

“…This reaction directly affects SM, PC, and ceramide as well as DAG levels. Three of us (55) have previously noted, using primary cerebral and peripheral VSMCs in culture, that a variation in [Mg 2ϩ ] o influences the cellular levels of SM, PC, DAG, and ceramide. Ceramide, either released as a consequence of SMase acting on SM and/or activation of either SPT or SMS or activation of CS, is now thought to play important roles in fundamental pathophysiologic processes such as cell proliferation, membrane receptor functions, angiogenesis, microcirculatory functions, immune inflammatory responses, cell adhesion, atherogenesis, senescence, programmed cell death (12,21,22,24,31,33,36,44,58,59,73,79,82,83), as well as cellular membrane transport and distribution of Mg 2ϩ in VSMCs (82).…”

mentioning

confidence: 99%

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Short-term magnesium deficiency upregulates ceramide synthase in cardiovascular tissues and cells: cross-talk among cytokines, Mg²⁺, NF-κB, and de novo ceramide

Altura

Shah²,

Shah³

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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BT. Short-term magnesium deficiency upregulates ceramide synthase in cardiovascular tissues and cells: crosstalk among cytokines, Mg 2ϩ , NF-B, and de novo ceramide. Am J Physiol Heart Circ Physiol 302: H319 -H332, 2012. First published October 7, 2011 doi:10.1152/ajpheart.00453.2011.-The present study tested the hypotheses that 1) short-term dietary deficiency (MgD) of magnesium (21 days) would result in the upregulation of ceramide synthase (CS) in left ventricular (LV), right ventricular, atrial, and aortic smooth muscle, as well as induce a synthesis/release of select cytokines and chemokines into the LV and aortic smooth muscle and serum; 2) exposure of primary cultured vascular smooth muscle cells (VSMCs) to low extracellular Mg concentration would lead to the synthesis/release of select cytokines/chemokines, activation of N-SMase, and the de novo synthesis of ceramide; and 3) inhibition of CS by fumonisin B1 (FB1) or inhibition of neutral sphingomyelinase (N-SMase) by scyphostatin (SCY) in VSMCs exposed to low Mg would result in reductions in the levels of the cytokines/chemokines and lowered levels of ceramide concomitant with inhibition of NF-B activation. The data indicated that shortterm MgD (10% normal dietary intake) resulted in the upregulation of CS in ventricular, atrial, and aortic smooth muscles coupled to the synthesis/release of 12 different cytokines/chemokines, as well as activation of NF-B in the LV and aortic smooth muscle and sera; even very low levels of water-borne Mg (e.g., 15 mg·l Ϫ1 ·day Ϫ1 ) either prevented or ameliorated the upregulation and synthesis of the cytokines/chemokines. Our experiments also showed that VSMCs exposed to low extracellular Mg resulted in the synthesis of 5 different cytokines and chemokines concomitant with synthesis/release of ceramide. However, inhibition of the synthesis and release of ceramide by either FB1 or SCY attenuated, markedly , the generation of ceramide, release of the cytokines/chemokines, and activation of NF-B (as measured by activated p65 and cRel). cardiac muscle; vascular muscle; p65; cRel; neutral sphingomyelinase; water-borne magnesium IMPROPER NUTRITION, HIGH CHOLESTEROL intake, and fatty diets are known to promote lipid deposition and accelerate growth and transformation of smooth muscle cells (SMCs) in the vascular wall (20,40,57). Over the past five decades, an accumulation of epidemiological and experimental data have indicated that a reduction in the dietary intake of Mg, as well as low Mg content in drinking water, is a risk factor for the development of hypertension, atherosclerosis, vasospasm, sudden cardiac death, stroke, and inflammatory conditions by ill-defined mechanisms (e.g., see Refs. 1,[4][5][6][17][18][19][27][28][29]35,38,46,48,49,63,64,65,67,72). Hypermagnesemic diets have been shown to ameliorate hypertension and atherogenesis (4,5,7,8,18,23,67). At present, the average dietary intake of Mg has declined from ϳ450 -485 mg/day in 1900 to ϳ185-235 mg/ day for large segments of the North American population (4, 30, ...

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Section: H324supporting

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Section: Influence Of An Inhibitor (Fumonisin B1) Of Cs On the De Novomentioning

confidence: 99%

mentioning

confidence: 93%

mentioning

confidence: 99%

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Short-term magnesium deficiency upregulates ceramide synthase in cardiovascular tissues and cells: cross-talk among cytokines, Mg²⁺, NF-κB, and de novo ceramide

Altura

Shah²,

Shah³

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Erythrocyte shape reversion from echinocytes to discocytes: Kinetics via fast‐measurement NMR diffusion‐diffraction

Pagès

Yau

Kuchel

2010

Magnetic Resonance in Med

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Pulsed field-gradient spin-echo (PGSE) NMR spectroscopy via q-space plots can characterize erythrocyte shapes and their evolution. The present study employed PGSE NMR to investigate shape reversion from advanced echinocytic to normal discocytic shapes due to depletion and then readdition of Mg 21 . In q-space plots of the data, the diffusion-diffraction minima disappeared for Mg 21 -depleted erythrocytes and reappeared during the shape recovery process, but with lower definition than for control cells. Shape estimates from PGSE NMR spectra and light microscopy were in excellent agreement after application of a scaling/correction factor. 31 P NMR was used to probe the biochemical processes activated in erythrocytes after depletion or addition of Mg 21; it showed the activation of the nonoxidative part of the pentose phosphate pathway. Experimental conditions were optimized to bypass this pathway without any influence on the q-space plots. The release of choline from phosphatidylcholine in the outer leaflet of the plasma membrane of the cells, observed using 1 H spin-echo NMR, showed a higher rate for shaperecovered than for control cells. This points to a change in phospholipid asymmetry in the plasma membrane. This variation in asymmetry affected the mean cell shape and hence influenced the average alignment of the erythrocytes with the static magnetic field and so affected the shapes of the qspace plots. Magn Reson Med 64:645-652, 2010. V C 2010 Wiley-Liss, Inc. Key words: 1 H spin-echo NMR; magnesium depletion; phospholipase D; pulsed-field gradient stimulated-echo NMR; q-space imaging; red blood cell shapeThe discocyte-to-echinocyte-to-spherocyte shape transition of the human erythrocyte (red blood cell; RBC) is emblematic of end-stage differentiation in cells, so it is notable that under special conditions of incubation the process can be reversed (1). Studying this reversion, and time course kinetics provides a different angle on the understanding of the biochemical and cytoskeletal-structural mechanisms underlying the discocyte-to-echinocyte-to-spherocyte shape transition. Another type of reversion has recently been reported for human RBCs, whereby membrane flickering that is inhibited with a sulfhydryl reagent can be reinstated with the membrane intercalating compound, diethyl phthalate (2). The physical techniques used in both studies hold promise for a better (quantitative) description of cell shape dynamics.The asymmetric distribution of lipids across the RBC membrane bilayer is an area of high-research activity (3). In normal human RBCs, the membrane bilayer is composed of amino-phospholipids in the inner monolayer (leaflet) while choline-containing phospholipids reside mostly in the outer leaflet (4). Normal RBCs have a characteristic biconcave disk shape. This is a meta-stable shape that involves the continuous adjustment of the asymmetric transbilayer lipid distribution. A change in the lipid location, and so a variation of the membrane asymmetry, appears to be involved in a change in the cell shap...

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Magnesium Modulates Contractile Responses of Rat Aorta to Thiocyanate: A Possible Relationship to Smoking-Induced Atherosclerosis

Zheng

Altura

et al. 1999

Toxicology and Applied Pharmacology

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Mg²⁺ modulates membrane sphingolipid and lipid second messenger levels in vascular smooth muscle cells

Cited by 52 publications

References 25 publications

Short-term magnesium deficiency upregulates ceramide synthase in cardiovascular tissues and cells: cross-talk among cytokines, Mg²⁺, NF-κB, and de novo ceramide

Short-term magnesium deficiency upregulates ceramide synthase in cardiovascular tissues and cells: cross-talk among cytokines, Mg²⁺, NF-κB, and de novo ceramide

Erythrocyte shape reversion from echinocytes to discocytes: Kinetics via fast‐measurement NMR diffusion‐diffraction

Magnesium Modulates Contractile Responses of Rat Aorta to Thiocyanate: A Possible Relationship to Smoking-Induced Atherosclerosis

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Mg2+ modulates membrane sphingolipid and lipid second messenger levels in vascular smooth muscle cells

Cited by 52 publications

References 25 publications

Short-term magnesium deficiency upregulates ceramide synthase in cardiovascular tissues and cells: cross-talk among cytokines, Mg2+, NF-κB, and de novo ceramide

Short-term magnesium deficiency upregulates ceramide synthase in cardiovascular tissues and cells: cross-talk among cytokines, Mg2+, NF-κB, and de novo ceramide

Erythrocyte shape reversion from echinocytes to discocytes: Kinetics via fast‐measurement NMR diffusion‐diffraction

Magnesium Modulates Contractile Responses of Rat Aorta to Thiocyanate: A Possible Relationship to Smoking-Induced Atherosclerosis

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Mg²⁺ modulates membrane sphingolipid and lipid second messenger levels in vascular smooth muscle cells

Short-term magnesium deficiency upregulates ceramide synthase in cardiovascular tissues and cells: cross-talk among cytokines, Mg²⁺, NF-κB, and de novo ceramide

Short-term magnesium deficiency upregulates ceramide synthase in cardiovascular tissues and cells: cross-talk among cytokines, Mg²⁺, NF-κB, and de novo ceramide