Effects of sphingolipids on erythroblastic maturation in the mouse

Scaro, J L; Miranda, C; Martín, B; Carrera, M

doi:10.1007/bf01949417

“…Consistent with our data, studies by Clayton et al showed an induction of erythropoiesis by sphingomyelin in bone marrow of rats in vitro (29). Moreover, Scaro and colleagues observed an increase of circulating reticulocytes after injecting mice with purified sphingomyelin in vivo (25).…”

Section: Discussionsupporting

confidence: 91%

“…Next, we determined sphingomyelin levels in bone marrow of Ac WT and Ac KO mice. Sphingomyelin is generated from ceramide by the activity of sphingomyelin synthases and has been shown to increase the number of reticulocytes in mice (25). While sphingomyelin levels were decreased in bone marrow of Ac KO mice compared to Ac WT mice at day 0 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Consistent with our data, studies by Clayton et al showed an induction of erythropoiesis by sphingomyelin in bone marrow of rats in vitro (29). Moreover, Scaro and colleagues observed an increase of circulating reticulocytes after injecting mice with purified sphingomyelin in vivo (25). Hence, one might speculate that the massive ceramide accumulation in Ac KO mice leads to an augmented SL turnover, resulting in elevated sphingomyelin concentrations in the bone marrow of Ac KO mice 7 days p.i.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The acid ceramidase/ceramide axis controls parasitemia in Plasmodium yoelii-infected mice by regulating erythropoiesis

Günther

¹

,

Hose

²

,

Schumacher

³

et al. 2022

Preprint

0

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Acid ceramidase (Ac) is part of the sphingolipid metabolism and responsible for the degradation of ceramide. As bioactive molecule, ceramide is involved in the regulation of many cellular processes. However, the impact of cell-intrinsic Ac activity and ceramide on the course of Plasmodium infection remains elusive. Here, we use Ac-deficient mice with ubiquitously increased ceramide levels to elucidate the role of endogenous Ac activity in a murine malaria model. Interestingly, ablation of Ac leads to alleviated parasitemia associated with decreased T cell responses in the early phase of Plasmodium yoelii (P. yoelii) infection. Mechanistically, we identified dysregulated erythropoiesis with reduced numbers of reticulocytes, the preferred host cells of P. yoelii, in Ac-deficient mice. Furthermore, we demonstrate that administration of the Ac inhibitor carmofur to wild type mice has similar effects on P. yoelii infection and erythropoiesis. Notably, therapeutic carmofur treatment after manifestation of P. yoelii infection is efficient in reducing parasitemia. Hence, our results provide evidence for the involvement of Ac and ceramide in controlling P. yoelii infection by regulating red blood cell development.

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“…The involvement of SM was further corroborated in 1986 by Scaro et al, when an extract of phospholipids from human plasma, as well as purified SM, were injected into mice. This resulted in an increased number of reticulocytes in circulation, suggestive of an increase in erythropoietic turnover [72]. Furthermore, Dallalio et al showed that ceramide inhibited CFU-E colony formation while S1P reversed this inhibition [73].…”

Section: Sphingolipids In Erythroid Differentiation and Erythrocytesmentioning

confidence: 99%

Sphingolipids in Hematopoiesis: Exploring Their Role in Lineage Commitment

Raza

¹

,

Salman

²

,

Luberto

³

2021

Cells

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Sphingolipids, associated enzymes, and the sphingolipid pathway are implicated in complex, multifaceted roles impacting several cell functions, such as cellular homeostasis, apoptosis, cell differentiation, and more through intrinsic and autocrine/paracrine mechanisms. Given this broad range of functions, it comes as no surprise that a large body of evidence points to important functions of sphingolipids in hematopoiesis. As the understanding of the processes that regulate hematopoiesis and of the specific characteristics that define each type of hematopoietic cells is being continuously refined, the understanding of the roles of sphingolipid metabolism in hematopoietic lineage commitment is also evolving. Recent findings indicate that sphingolipid alterations can modulate lineage commitment from stem cells all the way to megakaryocytic, erythroid, myeloid, and lymphoid cells. For instance, recent evidence points to the ability of de novo sphingolipids to regulate the stemness of hematopoietic stem cells while a substantial body of literature implicates various sphingolipids in specialized terminal differentiation, such as thrombopoiesis. This review provides a comprehensive discussion focused on the mechanisms that link sphingolipids to the commitment of hematopoietic cells to the different lineages, also highlighting yet to be resolved questions.

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“…Next, we determined sphingomyelin, sphingosine, and S1P levels in bone marrow of Ac WT and Ac KO mice. Sphingomyelin is generated from ceramide by the activity of sphingomyelin synthases and has been shown to increase the number of reticulocytes in mice ( Scaro et al, 1982 ). While sphingomyelin levels were decreased in bone marrow of Ac KO mice compared to Ac WT mice on day 0 ( Figure 5D , left panel), they were significantly enhanced on day 7 in the presence ( Figure 5D , right panel) and absence ( Figure 5—figure supplement 1 ) of the infection, correlating with increasing reticulocyte frequencies observed before.…”

Section: Resultsmentioning

confidence: 99%

The acid ceramidase/ceramide axis controls parasitemia in Plasmodium yoelii-infected mice by regulating erythropoiesis

Günther

¹

,

Hose

²

,

Abberger

³

et al. 2022

eLife

2

0

View full text Add to dashboard Cite

Acid ceramidase (Ac) is part of the sphingolipid metabolism and responsible for the degradation of ceramide. As bioactive molecule, ceramide is involved in the regulation of many cellular processes. However, the impact of cell-intrinsic Ac activity and ceramide on the course of Plasmodium infection remains elusive. Here, we use Ac-deficient mice with ubiquitously increased ceramide levels to elucidate the role of endogenous Ac activity in a murine malaria model. Interestingly, ablation of Ac leads to alleviated parasitemia associated with decreased T cell responses in the early phase of Plasmodium yoelii (P. yoelii) infection. Mechanistically, we identified dysregulated erythropoiesis with reduced numbers of reticulocytes, the preferred host cells of P. yoelii, in Ac-deficient mice. Furthermore, we demonstrate that administration of the Ac inhibitor carmofur to wild type mice has similar effects on P. yoelii infection and erythropoiesis. Notably, therapeutic carmofur treatment after manifestation of P. yoelii infection is efficient in reducing parasitemia. Hence, our results provide evidence for the involvement of Ac and ceramide in controlling P. yoelii infection by regulating red blood cell development.

show abstract

Effects of sphingolipids on erythroblastic maturation in the mouse

Cited by 3 publications

References 8 publications

The acid ceramidase/ceramide axis controls parasitemia in Plasmodium yoelii-infected mice by regulating erythropoiesis

The acid ceramidase/ceramide axis controls parasitemia in Plasmodium yoelii-infected mice by regulating erythropoiesis

Sphingolipids in Hematopoiesis: Exploring Their Role in Lineage Commitment

The acid ceramidase/ceramide axis controls parasitemia in Plasmodium yoelii-infected mice by regulating erythropoiesis

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