Dihydroceramide-desaturase-1-mediated caspase 9 activation through ceramide plays a pivotal role in palmitic acid-induced HepG2 cell apoptosis

Zhu, Qun; Yang, Jing; Zhu, Rongping; Jiang, Xin; Li, Wanlian; He, Songqing; Jin, Junfei

doi:10.1007/s10495-016-1267-9

Cited by 21 publications

(15 citation statements)

References 58 publications

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“…Moreover, in the BCL 2 family, BAX has a proapoptotic effect (Chen et al 2010;He et al 2018;Mu et al 2001). In the present study, the Caspase 3 activation (Zhu et al 2016) and BAX expression (He et al 2018) was upregulated after PA treatment, as previously shown in other studies. Based on these results, we concluded that PA can regulate Caspase 3 activation and BAX expression to affect cell apoptosis in Saos-2 cells.…”

Section: Discussionsupporting

confidence: 90%

Palmitic acid induces human osteoblast-like Saos-2 cell apoptosis via endoplasmic reticulum stress and autophagy

Yang

Guan

Lei

et al. 2018

Cell Stress and Chaperones

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Palmitic acid (PA) is the most common saturated long-chain fatty acid in food that causes cell apoptosis. However, little is known about the molecular mechanisms of PA toxicity. In this study, we explore the effects of PA on proliferation and apoptosis in human osteoblast-like Saos-2 cells and uncover the signaling pathways involved in the process. Our study showed that endoplasmic reticulum (ER) stress and autophagy are involved in PA-induced Saos-2 cell apoptosis. We found that PA inhibited the viability of Saos-2 cells in a dose- and time-dependent manner. At the same time, PA induced the expression of ER stress marker genes (glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)), altered autophagy-related gene expression (microtubule-associated protein 1 light chain 3 (LC3), ATG5, p62, and Beclin), promoted apoptosis-related gene expression (Caspase 3 and BAX), and affected autophagic flux. Inhibiting ER stress with 4-PBA diminished the PA-induced cell apoptosis, activated autophagy, and increased the expression of Caspase 3 and BAX. Inhibiting autophagy with 3-MA attenuated the PA and ER stress-induced cell apoptosis and the apoptosis-related gene expression (Caspase 3 and BAX), but seemed to have no obvious effects on ER stress, although the CHOP expression was downregulated. Taken together, our results suggest that PA-induced Saos-2 cell apoptosis is activated via ER stress and autophagy, and the activation of autophagy depends on the ER stress during this process.

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Section: Discussionsupporting

confidence: 90%

Palmitic acid induces human osteoblast-like Saos-2 cell apoptosis via endoplasmic reticulum stress and autophagy

Yang

Guan

Lei

et al. 2018

Cell Stress and Chaperones

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“…Both are precursors of apoptosis [ 42 – 44 ], possibly due to the homeostatic disturbance related to the low pH (3.5 to 4.5) that is characteristic of this vaginosis [ 5 ]. Additionally, the increase in the levels of palmitoleic acid and 1-oleoyl-cyclic phosphatidic acid in the CV group was consistent with the role of these acids on injured epithelial tissues, already described this relation in hepatic cells [ 45 ]. Our results showed the presence of these potential lipids biomarkers in CV group which can be inferred the possible relation of injured caused on the vaginal epithelium visualized on the Gram stain.…”

Section: Discussionsupporting

confidence: 85%

Vaginal lipidomics of women with vulvovaginal candidiasis and cytolytic vaginosis: A non-targeted LC-MS pilot study

et al. 2018

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ObjectiveTo characterize the lipid profile in vaginal discharge of women with vulvovaginal candidiasis, cytolytic vaginosis, or no vaginal infection or dysbiosis.DesignCross-sectional study.SettingGenital Infections Ambulatory, Department of Tocogynecology, University of Campinas, Campinas, São Paulo–Brazil.SampleTwenty-four women were included in this study: eight with vulvovaginal candidiasis, eight with cytolytic vaginosis and eight with no vaginal infections or dysbiosis (control group).MethodsThe lipid profile in vaginal discharge of the different study groups was determined by liquid chromatography-mass spectrometry and further analyzed with MetaboAnalyst 3.0 platform.Main outcome measuresVaginal lipids concentration and its correlation with vulvovaginal candidiasis and cytolytic vaginosis.ResultsPCA, PLS-DA and hierarchical clustering analyses indicated 38 potential lipid biomarkers for the different groups, correlating with oxidative stress, inflammation, apoptosis and integrity of the vaginal epithelial tissue. Among these, greater concentrations were found for Glycochenodeoxycholic acid-7-sulfate, O-adipoylcarnitine, 1-eicosyl-2-heptadecanoyl-glycero-3-phosphoserine, undecanoic acid, formyl dodecanoate and lipoic acid in the vulvovaginal candidiasis group; N–(tetradecanoyl)-sphinganine, DL-PPMP, 1-oleoyl-cyclic phosphatidic, palmitic acid and 5-aminopentanoic acid in the cytolytic vaginosis group; and 1-nonadecanoyl-glycero-3-phosphate, eicosadienoic acid, 1-stearoyl-cyclic-phosphatidic acid, 1-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphate, formyl 9Z-tetradecenoate and 7Z,10Z-hexadecadienoic acid in the control group.ConclusionsLipids related to oxidative stress and apoptosis were found in higher concentrations in women with vulvovaginal candidiasis and cytolytic vaginosis, while lipids related to epithelial tissue integrity were more pronounced in the control group. Furthermore, in women with cytolytic vaginosis, we observed higher concentrations of lipids related to bacterial overgrowth.

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“…It is well-known that SGMS2 is a key enzyme in the hemeostasis of Cer, which is tightly associated with cell apoptosis 5,11 . Many studies have revealed that ceramide plays a pivotal role in cell apoptosis via the P-AKT → caspase-3 → PARP signalling pathway in several types of diseases, including renal cell carcinoma 12 , hepatocellular carcinoma 13,14 and retinopathy 15 . To determine the mechanism underlying the SGMS2-induced increase in cell proliferation, we investigated the expression of Cer and activation of the Cer-associated apoptosis pathway.…”

Section: Resultsmentioning

confidence: 99%

Sphingomyelin synthase 2 promotes an aggressive breast cancer phenotype by disrupting the homoeostasis of ceramide and sphingomyelin

et al. 2019

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Breast cancer is the most common type of carcinoma in women worldwide, but the mechanisms underlying tumour development and progression remain unclear. Sphingomyelin synthase 2 (SGMS2) is a crucial regulator involved in ceramide (Cer) and sphingomyelin (SM) homoeostasis that is mostly studied for its role in lipid metabolism. Our primary study indicated that high SGMS2 expression is associated with breast cancer metastasis. Gain- and loss-of-function assays in vitro and in vivo revealed that SGMS2 promotes cancer cell proliferation by suppressing apoptosis through a Cer-associated pathway and promotes cancer cell invasiveness by enhancing epithelial-to-mesenchymal transition (EMT) initiation through the TGF-β/Smad signalling pathway. Further study determined that SGMS2 activated the TGF-β/Smad signalling pathway primarily by increasing TGF-β1 secretion, which was likely associated with aberrant expression of SM. Thus, our findings indicate that SGMS2-mediated activation of the TGF-β/Smad signalling pathway is important in breast cancer progression, which provides new insight into the mechanisms underlying breast cancer metastasis and suggests a possible anticancer therapy for breast cancer.

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Dihydroceramide-desaturase-1-mediated caspase 9 activation through ceramide plays a pivotal role in palmitic acid-induced HepG2 cell apoptosis

Cited by 21 publications

References 58 publications

Palmitic acid induces human osteoblast-like Saos-2 cell apoptosis via endoplasmic reticulum stress and autophagy

Palmitic acid induces human osteoblast-like Saos-2 cell apoptosis via endoplasmic reticulum stress and autophagy

Vaginal lipidomics of women with vulvovaginal candidiasis and cytolytic vaginosis: A non-targeted LC-MS pilot study

Sphingomyelin synthase 2 promotes an aggressive breast cancer phenotype by disrupting the homoeostasis of ceramide and sphingomyelin

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