Acute activation of acid ceramidase affects cytokine‐induced cytotoxicity in rat islet β‐cells

Zhu, Qun; Shan, Xiaohong; Miao, Heng; Lu, Yibing; Xu, Jiarong; Na, You; Liu, Chao; Liao, Duan‐Fang; Jin, Junfei

doi:10.1016/j.febslet.2009.05.047

Cited by 23 publications

(15 citation statements)

References 31 publications

(55 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, increases in ceramide mass under these conditions were only observed in RINm5F cells, 19 but not β-TC3 cells 17 . These modest or non-significant effects are perhaps consistent with observations that cytokines can activate both neutral and acidic ceramidases in β-cells, 21 , 22 which would tend to counteract any ceramide accumulation. Pharmacological inhibitors of ceramide synthesis or SMase activity also failed to alter IL-1β-stimulated responses in a rat β-cell line, 23 although the potentiation of IL-1β effects on cell death by TNFα might involve an enhanced sensitivity to basal acid SMase 24 .…”

Section: Sphingolipids and Type 1 Diabetessupporting

confidence: 83%

Roles of ceramide and sphingolipids in pancreatic β-cell function and dysfunction

Boslem

Meikle

Biden

2012

Islets

133

112

View full text Add to dashboard Cite

Recent technical advances have re-invigorated the study of sphingolipid metabolism in general, and helped to highlight the varied and important roles that sphingolipids play in pancreatic β-cells. Sphingolipid metabolites such as ceramide, glycosphingolipids, sphingosine 1-phosphate and gangliosides modulate many β-cell signaling pathways and processes implicated in β-cell diabetic disease such as apoptosis, β-cell cytokine secretion, ER-to-golgi vesicular trafficking, islet autoimmunity and insulin gene expression. They are particularly relevant to lipotoxicity. Moreover, the de novo synthesis of sphingolipids occurs on many subcellular membranes, in parallel to secretory vesicle formation, traffic and granule maturation events. Indeed, the composition of the plasma membrane, determined by the activity of neutral sphingomyelinases, affects β-cell excitability and potentially insulin exocytosis while another glycosphingolipid, sulfatide, determines the stability of insulin crystals in granules. Most importantly, sphingolipid metabolism on internal membranes is also strongly implicated in regulating β-cell apoptosis.

show abstract

Section: Sphingolipids and Type 1 Diabetessupporting

confidence: 83%

Roles of ceramide and sphingolipids in pancreatic β-cell function and dysfunction

Boslem

Meikle

Biden

2012

Islets

133

112

View full text Add to dashboard Cite

show abstract

“…Take together, our data suggest that NCDase inhibition is involved in Palm-induced apoptosis in INS-1 cells via blocking ceramide degradation and NCDase inhibition may be a novel pathway for ceramide accumulation, in addition to the ceramide synthesis de novo. Previously, we had reported that INS-1 cells exhibited basal NCDase activity [16], basal acid CDase activity was also detected in INS-1 cells and isolated rat islets [27]. In current study, we found that Palm treatment reduced mRNA and protein levels of NCDase, suppressing its activity and accumulating ceramide.…”

Section: Discussionsupporting

confidence: 53%

Neutral ceramidase activity inhibition is involved in palmitate-induced apoptosis in INS-1 cells

Luo

Feng

et al. 2017

Endocr J

Self Cite

View full text Add to dashboard Cite

Abstract. Neutral ceramidase (NCDase) is a class of ceramidases, a key enzyme in ceramide degradation. Recently, it was observed that NCDase activity was suppressed by saturated fatty acids to increase ceramide content in rat muscle. However, little is known about its changes in activity and roles in palmitate (Palm)-induced lipotoxicity in pancreatic β cells. Here, we demonstrated that Palm treatment significantly down-regulated NCDase activity, mRNA and protein levels in rat INS-1 cells. In addition, Palm caused a significant accumulation of ceramide, while SPH level remained unchanged, suggesting that inhibition of NCDase activity led to no change of SPH level after treatment with Palm for 24 h. Furthermore, NCDase overexpression significantly reduced Palm-induced apoptosis in INS-1 cells. Conversely, NCDase siRNA knockdown markedly exacerbated Palm-induced apoptosis. In conclusion, Palm treatment suppressed the activity of NCDase and down-regulated its mRNA and protein expression. Furthermore, NCDase inhibition was involved in Palm-induced apoptosis by blocking ceramide degradation in INS-1 cells.

show abstract

“…Increased sphingolipid metabolites that are observed during lipotoxicity also induce β-cell dysfunction, leading to apoptosis (49). For example, increased intracellular ceramide promotes an apoptotic cascade and initiates β-cell death in diabetic fatty rodent models of T2D in vivo and human β-cells in vitro (50–52). …”

Section: The Role Of Sphk/s1p Signalling In the Development Of Diamentioning

confidence: 99%

The role of sphingolipid signalling in diabetes-associated pathologies (Review)

Wadham

Sukocheva

2017

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Sphingosine kinase (SphK) is an important signalling enzyme that catalyses the phosphorylation of sphingosine (Sph) to form sphingosine-1-phosphate (S1P). The multifunctional lipid, S1P binds to a family of five G protein-coupled receptors (GPCRs). As an intracellular second messenger, S1P activates key signalling cascades responsible for the maintenance of sphingolipid metabolism, and has been implicated in the progression of cancer, and the development of other inflammatory and metabolic diseases. SphK and S1P are critical molecules involved in the regulation of various cellular metabolic processes, such as cell proliferation, survival, apoptosis, adhesion and migration. There is strong evidence supporting the critical roles of SphK and S1P in the progression of diabetes mellitus, including insulin sensitivity and insulin secretion, pancreatic β-cell apoptosis, and the development of diabetic inflammatory state. In this review, we summarise the current state of knowledge for SphK/S1P signalling effects, associated with the development of insulin resistance, pancreatic β-cell death and the vascular complications of diabetes mellitus.

show abstract

Acute activation of acid ceramidase affects cytokine‐induced cytotoxicity in rat islet β‐cells

Cited by 23 publications

References 31 publications

Roles of ceramide and sphingolipids in pancreatic β-cell function and dysfunction

Roles of ceramide and sphingolipids in pancreatic β-cell function and dysfunction

Neutral ceramidase activity inhibition is involved in palmitate-induced apoptosis in INS-1 cells

The role of sphingolipid signalling in diabetes-associated pathologies (Review)

Contact Info

Product

Resources

About