HSP60 Regulates Lipid Metabolism in Human Ovarian Cancer

Accumulating evidence demonstrates that cancer is an oxidative stress-related disease, and oxidative stress is closely linked with heat shock proteins (HSPs). Lipid oxidative stress is derived from lipid metabolism dysregulation that is closely associated with the development and progression of malignancies. This study sought to investigate regulatory roles of HSPs in fatty acid metabolism abnormality in ovarian cancer. Pathway network analysis of 5115 mitochondrial expressed proteins in ovarian cancer revealed various lipid metabolism pathway alterations, including fatty acid degradation, fatty acid metabolism, butanoate metabolism, and propanoate metabolism. HSP60 regulated the expressions of lipid metabolism proteins in these lipid metabolism pathways, including ADH5, ECHS1, EHHADH, HIBCH, SREBP1, ACC1, and ALDH2. Further, interfering HSP60 expression inhibited migration, proliferation, and cell cycle and induced apoptosis of ovarian cancer cells in vitro. In addition, mitochondrial phosphoproteomics and immunoprecipitation-western blot experiments identified and confirmed that phosphorylation occurred at residue Ser70 in protein HSP60, which might regulate protein folding of ALDH2 and ACADS in ovarian cancers. These findings clearly demonstrated that lipid metabolism abnormality occurred in oxidative stress-related ovarian cancer and that HSP60 and its phosphorylation might regulate this lipid metabolism abnormality in ovarian cancer. It opens a novel vision in the lipid metabolism reprogramming in human ovarian cancer.

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Acyl-CoA Medium-Chain Synthetase-3 Promotes Chemosensitivity of Ovarian Cancer through the Inhibition of PI3K/AKT Signaling Pathway

10.21203/rs.3.rs-1069550/v1 ◽

2021 ◽

Author(s):

Yuanyuan An ◽

Hua Duan

Keyword(s):

Ovarian Cancer ◽

Fatty Acid ◽

Cancer Cells ◽

Signaling Pathway ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Immune Status ◽

Akt Signaling ◽

Ovarian Cancer Cells ◽

Akt Signaling Pathway

Abstract Introduction: Dysregulation of fatty acid metabolism often occurs in tumor, which mainly constitutes of fatty acid synthesis and oxidation. In recent years, studies found that fatty acid metabolism participated in regulation of tumor immune microenvironment, which further influenced the progress of cancer. Thus, it is important to explore the key fatty acid metabolism-related molecules, which not only affects the prognosis of ovarian cancer, but also shows a close correlation with immune microenvironment of cancer.Methods: Database from TCGA was used to explore the fatty acid metabolism-related molecules, which correlated with the prognosis of ovarian cancer using univariate and multivariate cox proportional regression model. Nomogram was constructed to predict the prognostic probability based on ACSM3 and clinicopathological parameters. GDSC database was used to investigate the chemosensitivity of ovarian cancer cells. The correlation between ACSM3 and immune status of ovarian cancer was analyzed by TIMER and TISIDB online tools. In addition, CCK8 assay was used to investigate the chemosensitivity of ovarian cancer cells, real time-PCR and western blot were used to investigate the expression of chemoresistance-related genes.Results: ACSM3 worked as an independent favorable prognostic molecule through univariate and multivariate cox regression analysis. For the use in clinical, nomogram was constructed, and higher expression of ACSM3 showed better prognosis. We found that ACSM3 could regulate PI3K/AKT signaling, and GDSC database showed that PI3K/AKT inhibitor could promote the chemosensitivity of ovarian cancer cells. In addition, the expression of ACSM3 showed significantly correlated with the immune status of ovarian cancer. In vitro experiments showed that ACSM3 can promote the chemosensitivity of ovarian cancer cells by inhibiting PI3K/AKT signaling pathway.Conclusion: Our results showed that ACSM3 acted as a favorable prognostic-related biomarker for ovarian cancer, which could promote chemosensitivity of ovarian cancer through inhibiting PI3K/AKT signaling pathway. This might be due to participate in regulating immune status of ovarian cancer microenvironment.

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RiboTag translatomic profiling of Drosophila oenocytes under aging and oxidative stress

10.1101/272179 ◽

2018 ◽

Author(s):

Kerui Huang ◽

Wenhao Chen ◽

Fang Zhu ◽

Hua Bai

Keyword(s):

Oxidative Stress ◽

Fatty Acid ◽

Lipid Metabolism ◽

Stress Response ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Fat Body ◽

Mapk Signaling ◽

Age Related ◽

And Oxidative Stress

AbstractBackgroundAging is accompanied with loss of tissue homeostasis and accumulation of cellular damages. As one of the important metabolic centers, aged liver shows altered lipid metabolism, impaired detoxification pathway, increased inflammation and oxidative stress response. However, the mechanisms for these age-related changes still remain unclear. In fruit flies, Drosophila melanogaster, liver-like functions are controlled by two distinct tissues, fat body and oenocytes. Although the role of fat body in aging regulation has been well studied, little is known about how oenocytes age and what are their roles in aging regulation. To address these questions, we used cell-type-specific ribosome profiling (RiboTag) to study the impacts of aging and oxidative stress on oenocyte translatome in Drosophila.ResultsWe show that aging and oxidant paraquat significantly increased the levels of reactive oxygen species (ROS) in adult oenocytes of Drosophila, and aged oenocytes exhibited reduced sensitivity to paraquat treatment. Through RiboTag sequencing, we identified 3324 and 949 differentially expressed genes in oenocytes under aging and paraquat treatment, respectively. Aging and paraquat exhibit both shared and distinct regulations on oenocyte translatome. Among all age-regulated genes, mitochondrial, proteasome, peroxisome, fatty acid metabolism, and cytochrome P450 pathways were down-regulated, whereas DNA replication and glutathione metabolic pathways were up-regulated. Interestingly, most of the peroxisomal genes were down-regulated in aged oenocytes, including peroxisomal biogenesis factors and beta-oxidation genes. Further analysis of the oenocyte translatome showed that oenocytes highly expressed genes involving in liver-like processes (e.g., ketogenesis). Many age-related transcriptional changes in oenocytes are similar to aging liver, including up-regulation of Ras/MAPK signaling pathway and down-regulation of peroxisome and fatty acid metabolism.ConclusionsOur oenocyte-specific translatome analysis identified many genes and pathways that are shared between Drosophila oenocytes and mammalian liver, highlighting the molecular and functional similarities between the two tissues. Many of these genes are altered in both aged oenocytes and aged liver, suggesting a conserved molecular mechanism underlying oenocyte and liver aging. Thus, our translatome analysis will contribute significantly to the understanding of oenocyte biology, and its role in lipid metabolism, stress response and aging regulation.

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In vitro lipid metabolism in the rat pancreas II. Effects of secretagogues on fatty acid metabolism, net lipolysis and ATP levels

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism ◽

10.1016/0005-2760(79)90235-2 ◽

1979 ◽

Vol 574 (3) ◽

pp. 391-403 ◽

Cited By ~ 8

Author(s):

Piedad Calderon ◽

Jacques Furnelle ◽

Jean Cristophe

Keyword(s):

Fatty Acid ◽

Lipid Metabolism ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Rat Pancreas ◽

Atp Levels

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Lipid and glucose metabolism in hepatocyte cell lines and primary mouse hepatocytes: a comprehensive resource for in vitro studies of hepatic metabolism

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00365.2018 ◽

2019 ◽

Vol 316 (4) ◽

pp. E578-E589 ◽

Cited By ~ 15

Author(s):

Shilpa R. Nagarajan ◽

Moumita Paul-Heng ◽

James R. Krycer ◽

Daniel J. Fazakerley ◽

Alexandra F. Sharland ◽

...

Keyword(s):

Fatty Acid ◽

Glucose Metabolism ◽

Cell Lines ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Primary Hepatocytes ◽

Primary Mouse Hepatocytes ◽

Primary Mouse ◽

Mouse Hepatocytes

The liver is a critical tissue for maintaining glucose, fatty acid, and cholesterol homeostasis. Primary hepatocytes represent the gold standard for studying the mechanisms controlling hepatic glucose, lipid, and cholesterol metabolism in vitro. However, access to primary hepatocytes can be limiting, and therefore, other immortalized hepatocyte models are commonly used. Here, we describe substrate metabolism of cultured AML12, IHH, and PH5CH8 cells, hepatocellular carcinoma-derived HepG2s, and primary mouse hepatocytes (PMH) to identify which of these cell lines most accurately phenocopy PMH basal and insulin-stimulated metabolism. Insulin-stimulated glucose metabolism in PH5CH8 cells, and to a lesser extent AML12 cells, responded most similarly to PMH. Notably, glucose incorporation in HepG2 cells were 14-fold greater than PMH. The differences in glucose metabolic activity were not explained by differential protein expression of key regulators of these pathways, for example glycogen synthase and glycogen content. In contrast, fatty acid metabolism in IHH cells was the closest to PMHs, yet insulin-responsive fatty acid metabolism in AML12 and HepG2 cells was most similar to PMH. Finally, incorporation of acetate into intracellular-free cholesterol was comparable for all cells to PMH; however, insulin-stimulated glucose conversion into lipids and the incorporation of acetate into intracellular cholesterol esters were strikingly different between PMHs and all tested cell lines. In general, AML12 cells most closely phenocopied PMH in vitro energy metabolism. However, the cell line most representative of PMHs differed depending on the mode of metabolism being investigated, and so careful consideration is needed in model selection.

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Characterization of a Hyaluronic Acid and Folic Acid-Based Hydrogel for Cisplatin Delivery: Antineoplastic Effect in Human Ovarian Cancer Cells in vitro

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2021.120899 ◽

2021 ◽

pp. 120899

Author(s):

Simona Serini ◽

Roberta Cassano ◽

Matilde Bruni ◽

Camilla Servidio ◽

Gabriella Calviello ◽

...

Keyword(s):

Ovarian Cancer ◽

Hyaluronic Acid ◽

Folic Acid ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Antineoplastic Effect

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E-cadherin promotes proliferation of human ovarian cancer cells in vitro via activating MEK/ERK pathway

Acta Pharmacologica Sinica ◽

10.1038/aps.2012.30 ◽

2012 ◽

Vol 33 (6) ◽

pp. 817-822 ◽

Cited By ~ 22

Author(s):

Ling-ling Dong ◽

Lian Liu ◽

Chun-hong Ma ◽

Ji-sheng Li ◽

Chao Du ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Erk Pathway ◽

E Cadherin

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In vitro effect of lysophosphatidic acid on proliferation, invasion and migration of human ovarian cancer cells

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v17i2.4 ◽

2018 ◽

Vol 17 (2) ◽

pp. 219

Author(s):

Qingfu Wang ◽

Lixin Zhu ◽

Aiping Qin ◽

Tiefeng Chen ◽

Jinpen Li ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Lysophosphatidic Acid ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Invasion And Migration ◽

And Migration

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Phenolic Compounds Reduce the Fat Content in Caenorhabditis elegans by Affecting Lipogenesis, Lipolysis, and Different Stress Responses

Pharmaceuticals ◽

10.3390/ph13110355 ◽

2020 ◽

Vol 13 (11) ◽

pp. 355

Author(s):

Paula Aranaz ◽

David Navarro-Herrera ◽

María Zabala ◽

Ana Romo-Hualde ◽

Miguel López-Yoldi ◽

...

Keyword(s):

Oxidative Stress ◽

Fatty Acid ◽

Phenolic Compounds ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Lipid Mobilization ◽

C Elegans ◽

Unfolded Protein ◽

Reducing Activity ◽

Protein Response

Supplementation with bioactive compounds capable of regulating energy homeostasis is a promising strategy to manage obesity. Here, we have screened the ability of different phenolic compounds (myricetin, kaempferol, naringin, hesperidin, apigenin, luteolin, resveratrol, curcumin, and epicatechin) and phenolic acids (p-coumaric, ellagic, ferulic, gallic, and vanillic acids) regulating C. elegans fat accumulation. Resveratrol exhibited the strongest lipid-reducing activity, which was accompanied by the improvement of lifespan, oxidative stress, and aging, without affecting worm development. Whole-genome expression microarrays demonstrated that resveratrol affected fat mobilization, fatty acid metabolism, and unfolded protein response of the endoplasmic reticulum (UPRER), mimicking the response to calorie restriction. Apigenin induced the oxidative stress response and lipid mobilization, while vanillic acid affected the unfolded-protein response in ER. In summary, our data demonstrates that phenolic compounds exert a lipid-reducing activity in C. elegans through different biological processes and signaling pathways, including those related with lipid mobilization and fatty acid metabolism, oxidative stress, aging, and UPR-ER response. These findings open the door to the possibility of combining them in order to achieve complementary activity against obesity-related disorders.

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Identification of differentially expressed genes and pathways between intramuscular and abdominal fat-derived preadipocyte differentiation of chickens in vitro

BMC Genomics ◽

10.1186/s12864-019-6116-0 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 8

Author(s):

Meng Zhang ◽

Fang Li ◽

Xiang-fei Ma ◽

Wen-ting Li ◽

Rui-rui Jiang ◽

...

Keyword(s):

Fatty Acid ◽

Lipid Metabolism ◽

Differentially Expressed Genes ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Adipogenic Differentiation ◽

Abdominal Fat ◽

Receptor Interaction ◽

Preadipocyte Differentiation ◽

Factors Affecting

Abstract Background The distribution and deposition of fat tissue in different parts of the body are the key factors affecting the carcass quality and meat flavour of chickens. Intramuscular fat (IMF) content is an important factor associated with meat quality, while abdominal fat (AbF) is regarded as one of the main factors affecting poultry slaughter efficiency. To investigate the differentially expressed genes (DEGs) and molecular regulatory mechanisms related to adipogenic differentiation between IMF- and AbF-derived preadipocytes, we analysed the mRNA expression profiles in preadipocytes (0d, Pre-) and adipocytes (10d, Ad-) from IMF and AbF of Gushi chickens. Results AbF-derived preadipocytes exhibited a higher adipogenic differentiation ability (96.4% + 0.6) than IMF-derived preadipocytes (86.0% + 0.4) (p < 0.01). By Ribo-Zero RNA sequencing, we obtained 4403 (2055 upregulated and 2348 downregulated) and 4693 (2797 upregulated and 1896 downregulated) DEGs between preadipocytes and adipocytes in the IMF and Ad groups, respectively. For IMF-derived preadipocyte differentiation, pathways related to the PPAR signalling pathway, ECM-receptor interaction and focal adhesion pathway were significantly enriched. For AbF-derived preadipocyte differentiation, the steroid biosynthesis pathways, calcium signaling pathway and ECM-receptor interaction pathway were significantly enriched. A large number of DEGs related to lipid metabolism, fatty acid metabolism and preadipocyte differentiation, such as PPARG, ACSBG2, FABP4, FASN, APOA1 and INSIG1, were identified in our study. Conclusion This study revealed large transcriptomic differences between IMF- and AbF-derived preadipocyte differentiation. A large number of DEGs and transcription factors that were closely related to fatty acid metabolism, lipid metabolism and preadipocyte differentiation were identified in the present study. Additionally, the microenvironment of IMF- and AbF-derived preadipocyte may play a significant role in adipogenic differentiation. This study provides valuable evidence to understand the molecular mechanisms underlying adipogenesis and fat deposition in chickens.

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