Ask about this productRelated genes to: SMPD2 Blocking Peptide
- Gene:
- SMPD2 NIH gene
- Name:
- sphingomyelin phosphodiesterase 2
- Previous symbol:
- -
- Synonyms:
- nSMase, ISC1
- Chromosome:
- 6q21
- Locus Type:
- gene with protein product
- Date approved:
- 1998-06-22
- Date modifiied:
- 2015-12-10
Related products to: SMPD2 Blocking Peptide
Related articles to: SMPD2 Blocking Peptide
- Altered ceramide accumulation contributes to skeletal muscle insulin resistance, but mechanisms underlying fibre-type-specific susceptibility remain unclear. We hypothesized that fibre-type-specific ceramide metabolism governs vulnerability to lipid-induced insulin resistance. Lipidomics and quantification of ceramide-pathway enzymes were performed in mouse skeletal muscles with distinct fibre-type composition (oxidative, mixed and glycolytic) from control-diet (n = 12) and high-fat-diet (HFD; n = 12) mice. In humans, lipidomics and enzyme profiling were done in vastus lateralis biopsies from 36 adults stratified into oxidative or glycolytic phenotypes; insulin sensitivity was determined by glucose tolerance testing. siRNA-mediated silencing of SGMS1 and SGMS2 followed by lipidomics probed sphingomyelin-ceramide cycling in human myoblasts. In mouse muscle, ceramide composition rather than total content, differed by fibre type: oxidative muscle was enriched in very-long-chain ceramides, whereas glycolytic and mixed muscles contained higher C18-ceramides, paralleled by fibre-type-specific expression of enzymes involved in de novo synthesis and sphingomyelin-ceramide cycling. HFD induced ceramide remodelling, with C18-ceramides accumulating in oxidative and mixed muscles and very-long-chain species decreasing in glycolytic muscle; among all assessed enzymes, only SGMS2 was significantly downregulated in oxidative muscle. In humans, an oxidative phenotype associated with higher very-long-chain ceramides and insulin sensitivity, whereas a glycolytic phenotype displayed higher C16-18 ceramides, higher SGMS1 and SMPD2 expression, and lower insulin sensitivity. Elastic net regression identified C16-18 ceramides and galactosylceramides as negative predictors of insulin sensitivity. SGMS2 silencing caused broader ceramide accumulation than SGMS1 silencing, supporting a central role for SGMS2-mediated sphingomyelin-ceramide cycling in limiting ceramide burden. - Source: PubMed
Publication date: 2026/02/16
Eurén TovaFlockhart MikaelStrmeň TimotejZhou XinHorwath OscarApró WilliamBlackwood Sarah JTischer DominikMoberg MarcusSteneberg PärEdlund HelenaKatz AbramChorell Elin - Radiotherapy failure often arises from tumor repopulation by treatment-resistant cancer cells. Following irradiation, cancer cells can undergo endoreplication to form polyploid giant cancer cells (PGCCs)-radiation-persistent cells capable of generating progeny through a virus-like asymmetric budding process. While such membrane budding is evolutionarily conserved across archaea, viruses, and eukaryotic cells, its molecular mechanism in cancer remains poorly defined. Here, a radiation-induced SNCG-FLOT2-CHMP4B signaling axis is identified as a key regulator of PGCC budding. Mechanistically, ASAH1 and SMPD2 maintain sphingolipid metabolic balance, while FLOT2 drives germination at lipid raft-enriched membrane microdomains, followed by CHMP4B-dependent abscission to release daughter cells. Disrupting these lipid raft structures-via statins or anti-PCSK9 antibodies-impairs budding, suppresses PGCC-derived tumor repopulation, and enhances radiosensitivity in vitro and in vivo. This findings uncover a conserved membrane remodeling program underlying PGCC budding and establish lipid raft disruption as a promising therapeutic approach to prevent tumor recurrence after radiotherapy. Clinically available lipid-lowering agents may thus serve as innovative radiosensitizers to improve radiotherapy outcomes. - Source: PubMed
Publication date: 2025/12/02
Deng ZhengSun HaoranCheng JinZhao RuyiXie JianzhuSong YanweiZhao YucuiLin ChenweiHu BinjieGong YanpingLin JunHe SijiaLuo YuntaoZhao MinghuiWang YiweiJiao MingYang YuqinLi JikunXia ShujieLi ChuanyuanHuang Qian - Small extracellular vesicles (sEVs) function as critical regulators of ovarian follicular development. Although several pathways, including one involving neutral sphingomyelinase (nSMase), contribute to sEV production, the specific pathway active in ovarian follicles has not been clearly identified. In this study, we investigated GW4869, a specific inhibitor of nSMase activity, to determine its impact on sEV production by mouse mural granulosa cells (MGCs), the primary source of follicular sEVs. We also examined how nSMase inhibition affects the in vitro growth of oocyte‒granulosa cell complexes (OGCs) derived from secondary follicles. Transcripts encoding nSMases (Smpd2 and Smpd4) were detected in MGCs, and GW4869 treatment significantly reduced sEV production in MGC monolayer cultures. Control OGCs developed into antral follicle-like structures, with the antrum-like structure separating granulosa cells into cumulus-like and MGC-like cells. However, GW4869 treatment impaired OGC development. MGC-like cells from GW4869-treated OGCs exhibited significantly lower Cyp19a1 levels, whereas adding MGC-derived sEVs promoted Cyp19a1 expression. These results suggest that nSMase activity, likely involving Smpd2 and Smpd4, is required for sEV production by MGCs and that follicular sEVs may regulate Cyp19a1 expression in MGCs. - Source: PubMed
Matsushita KodaiMatsuno YutaKita KazumaIchikawa AyakaMaruyama NatsumiFujii WataruEndo TsutomuSugiura Koji - The gene Sphingomyelin phosphodiesterase 2 (SMPD2), a member of the SMPD family, plays crucial roles in cell cycle progression and cell proliferation. However, the pathogenic implications of SMPD2 across various cancers remain poorly understood. Its potential involvement in lipid metabolism and immune-related processes within the tumor microenvironment has not been systematically characterized. To address these gaps, we conducted a comprehensive pan-cancer analysis of SMPD2. Using a range of computational tools, we investigated its role in tumor immune infiltration, immune evasion, tumor progression, therapy response, and prognosis across various cancer types. Our findings suggest that SMPD2 is widely expressed across cancers in The Cancer Genome Atlas (TCGA) and its expression levels are associated with tumor stages and clinical outcomes. Additionally, SMPD2 was found to be involved in tumor immune evasion across different cancer types. The methylation status of SMPD2 was inversely correlated with its mRNA expression levels, which were associated with dysfunctional T cell phenotypes and worse prognoses in diverse cancer cohorts. Furthermore, SMPD2 expression was linked to heterogeneous therapeutic outcomes across multiple cancer types, including variable responses to immune checkpoint blockade. Interestingly, SMPD2 demonstrated superior predictive capacity for treatment response and overall survival in immune checkpoint blockade sub-cohorts compared to three of the seven established biomarkers. While functional experiments are warranted, our results provide a data-driven, pan-cancer landscape of SMPD2 expression and its potential relevance to immune modulation and clinical outcomes Overall, SMPD2 may serve as a candidate biomarker for cancer prognosis and therapeutic response, and a potential target for future mechanistic studies. - Source: PubMed
Publication date: 2025/09/29
Li Qing-YanHuang Jia-MingYuan XiangGuo Hui-LongZhang WeiChen Yu-ChuanLi Yi-YiSong Ze - : Myristic acid (MA), a 14-carbon saturated fatty acid, serves as a precursor for the synthesis of non-canonical d16-sphingoid bases via its activated form, C14:0-CoA. However, its broader regulatory role in sphingolipid (SL) metabolism remains poorly defined. : Using HepG2 cells treated with 50 μM MA, we found that sphingolipidomic analysis revealed reprogrammed sphingolipid metabolism. : In the canonical d18-SL pathway, MA directs its activated product C14:0-CoA into ceramide -acyl chains and downstream metabolites-especially d18:1-C14:0 hexosylceramide. Concurrently, in the non-canonical d16-SL pathway, MA promotes d16-SL synthesis, especially d16:1-ceramides (Cer), d16:1-hexosylceramides (HexCer), and d16:1-C14:0 lactosylceramide. MA treatment further induced a coordinated shift in cellular sphingolipid pools, characterized by a significant increase in total ceramide levels (encompassing both d16- and d18-species) alongside concurrent reductions in total sphingomyelin (SM) contents. At the gene transcriptional level, MA significantly suppressed mRNA expression while markedly upregulating and mRNA levels. : Collectively, these findings position MA as a potent regulator of sphingolipid homeostasis, orchestrating dual pathway modulation: disrupting canonical d18-SL equilibrium through the selective enrichment of -acyl C14:0-containing SLs, and activating non-canonical d16-SL synthesis. This dual pathway regulation reveals that dietary saturated fatty acids exploit sphingolipid subnetworks to regulate lipid metabolism. The interplay between dietary fatty acids and sphingolipid metabolism still requires deeper exploration. Our findings offer preliminary insights into their roles in regulating both normal and disease-associated lipid metabolism, setting the stage for subsequent mechanistic investigations. - Source: PubMed
Publication date: 2025/09/05
You YunfeiZeng QingheHu ZhenyingChen YuZhan MengminWang YanluDuan Jingjing