Molecular Pathways of Different Types of Cell Death: Many Roads to Death

Krysko, Dmitri V.; Kaczmarek, Agnieszka; Vandenabeele, Peter

doi:10.1007/978-1-4020-9293-0_1

Cited by 4 publications

(7 citation statements)

References 176 publications

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“…Recently, we provided convincing evidence that short-term MgD produces apoptosis, at least in ventricular, atrial, and vascular muscle cells via the extrinsic pathway (6,30). However, the present study that demonstrates profound release of free Cyto c (presumably from mitochondria) suggests rather strongly that MgD also produces apoptosis in these cardiovascular cells via the intrinsic pathway of programmed cell death, particularly as a release of free Cyto c is a sine qua non for identifying (and implicating) this pathway (24,28). Our new findings suggest that the activation of this intrinsic pathway is most likely brought about as a consequence of a generation of ceramides because of the activation of SPT 1 and SPT 2 by low plasma and cellular ionized Mg.…”

Section: H935contrasting

confidence: 57%

“…Our new findings suggest that the activation of this intrinsic pathway is most likely brought about as a consequence of a generation of ceramides because of the activation of SPT 1 and SPT 2 by low plasma and cellular ionized Mg. This suggestion is strengthened by our experiments on primary cultured cerebral and vascular smooth muscle cells, which show that low levels of Mg 2ϩ activate the protein apoptotic protease factor-1, which must be activated by a binding to free Cyto c (28). Such binding between these molecules must take place in order for apopototic events to occur via the intrinsic pathway (28).…”

Section: H935mentioning

confidence: 69%

“…We designed experiments to determine 1) whether a shortterm MgD would lead to the activation of both SPT 1 and SPT 2, concomitant with reduction in serum levels of SM and ionized Mg, as well as increased cellular levels of Cyto c (indicative of the intrinsic mitochondrial pathway of apoptosis) (28) and 2) whether imbibing low levels of a water-soluble Mg salt in drinking water would inhibit or reverse these predicted effects of a dietary deficiency of Mg.…”

mentioning

confidence: 99%

“…Ceramides, released as a consequence of sphingomyelinase (SMase) acting on SM or as a consequence of the activation of SPT (a de novo synthetic pathway) (34), are now thought to play important roles in fundamental processes such as angiogenesis, membrane-receptor functions, cell proliferation, microcirculatory functions, cell adhesion, atherogenesis, immunoinflammatory responses, excitation-contraction coupling in smooth muscles, and programmed cell death (4,10,21,22,27,43,44,55,62,65). Since a de novo synthesis of ceramides via the SPT pathway has been linked to the mitochondrial (intrinsic) pathway of apoptosis in certain cells, promoting the release of cytochrome c (Cyto c) (28), we wondered whether such a pathway is present in cardiovascular tissues in short-term Mg deficiency (MgD).…”

mentioning

confidence: 99%

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Magnesium deficiency upregulates serine palmitoyl transferase (SPT 1 and SPT 2) in cardiovascular tissues: relationship to serum ionized Mg and cytochromec

Altura¹,

Shah²,

Zhiqiang

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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The present work tested the hypothesis that a short-term dietary deficiency of magnesium (Mg) (21 days) in rats would result in the upregulation of the two major subunits of serine palmitoyl-CoA-transferase, serine palmitoyl transferase (SPT 1) and SPT 2 (the rate-limiting enzymes responsible for the de novo biosynthesis of ceramides) in left ventricular, right ventricular, and atrial heart muscle and abdominal aortic smooth muscle, as well as induce a reduction in serum sphingomyelin concomitant with the release of mitochondrial cytochrome c (Cyto c) in these tissues. Our data indicate that short-term Mg deficiency (MgD) resulted in an upregulation of SPT 1 and SPT 2, concomitant with a very significant release of Cyto c in left ventricular, right ventricular, atrial, and abdominal aortic smooth muscle. Short-term MgD also produced a lowering of serum sphingomyelin and ionized Mg. The greater the reduction in serum ionized Mg, the greater the upregulation of SPT 1 and 2 and the more the increase in free Cyto c. The data suggest that MgD, most likely, causes a biosynthesis of ceramides via two pathways in cardiovascular tissues, viz., via the activation of serine palmitoyl-CoA-transferase and sphingomyelinase, which lead to apoptotic events via intrinsic (present study) and extrinsic pathways (previous studies). Low levels of drinking water Mg were cardio- and vasculoprotective.

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Section: H935contrasting

confidence: 57%

Section: H935mentioning

confidence: 69%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Magnesium deficiency upregulates serine palmitoyl transferase (SPT 1 and SPT 2) in cardiovascular tissues: relationship to serum ionized Mg and cytochromec

Altura¹,

Shah²,

Zhiqiang

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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show abstract

“…SPT is a heterodimer of 53-kDa SPT-1 and 63-kDa SPT 2 subunits [60,61], both of which are bound to the endoplasmic reticulum [62]. An upregulation of SPT activity has been hypothesized to play a role in apoptosis [63], cell death events taking place in atherogenesis [41,42,64 ].…”

Section: Causative Events and Pathways Leading To Inflammationatherogmentioning

confidence: 99%

Potential Roles of Magnesium Deficiency in Inflammation and Atherogenesis: Importance and Cross-talk of Platelet-Activating Factor and Ceramide

Bm¹

2016

J Clin Exp Cardiolog

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Epidemiologic studies in North America and Europe have shown that people consuming Western-type diets are low in magnesium (Mg) content (i.e., < 30 -65% of the RDA for Mg); most such diets in the USA show that 60 -80% of Americans are consuming only 185 -235 mg/day of Mg. Low Mg content in areas of soft-water, and Mg-poor soil, is associated with high incidences of ischemic heart disease (IHD), coronary artery disease, hypertension, and sudden cardiac death (SCD). It is clear that the leading underlying cause of death worldwide is atherosclerosis. Importantly, both animal and human studies have shown an inverse relationship between dietary intake of Mg and atherosclerosis. The myocardial level of Mg has consistently been observed to be lower in subjects dying from IHD and SCD in soft-water areas than those in hard-water areas. Over the past 20 years, our laboratories, using several types of primary cultured vascular smooth muscle (VSM) cells, and myocardial cells, demonstrated that declining levels of extracellular Mg ([Mg 2+ ] 0 ) activated several enzymatic pathways to produce increases in cellular sphingolipids, particularly ceramides which are known to exert numerous types of cardiovascular manifestations including inflammatory effects ; the latter play important roles in atherogenesis and cardiovascular diseases. Approximately 20 years ago, we reported that low [Mg 2+ ] 0 caused formation of platelet-activating factor (PAF) as well as other types of PAF-like molecules and suggested that these molecules might be causative agents in low Mg 2+ -induced IHD and SCD. Herein, we review results and data from our labs which strongly support roles for ceramides, PAF and PAF-like lipids in low [Mg 2+ ] 0 -induced IHD and SCD.

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