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JOURNAL ARTICLE
Sonsoles Alonso, Gustavo Cebrián, Keshav Gautam, Jessica Iglesias-Moya, Cecilia Martínez, Manuel Jamilena
A Cucurbita pepo mutant with multiple defects in growth and development has been identified and characterized. The mutant dwfcp displayed a dwarf phenotype with dark green and shrinking leaves, shortened internodes and petioles, shorter but thicker roots and greater root biomass, and reduced fertility. The causal mutation of the phenotype was found to disrupt gene Cp4.1LG17g04540 , the squash orthologue of the Arabidopsis brassinosteroid (BR) biosynthesis gene DWF5 , encoding for 7-dehydrocholesterol reductase...
April 2024: Horticulture Research
#2
JOURNAL ARTICLE
Yanfeng Wang, Jiaxin Fan, Yongcheng Liu, Jie Du, Boyu Liang, Huxia Wang, Zhangjun Song
BACKGROUND: Energy metabolism has a complex intersection with pathogenesis and development of breast cancer (BC). This allows for the possibility of identifying energy-metabolism-related genes (EMRGs) as novel prognostic biomarkers for BC. 7-dehydrocholesterol reductase (DHCR7) is a key enzyme of cholesterol biosynthesis involved in many cancers, and in this paper, we investigate the effects of DHCR7 on the proliferation and mitochondrial function of BC. METHODS: EMRGs were identified from the Gene Expression Omnibus (GEO) and MSigDB databases using bioinformatics methods...
March 22, 2024: Aging
#3
JOURNAL ARTICLE
Naoya Yamada, Tadayoshi Karasawa, Junya Ito, Daisuke Yamamuro, Kazushi Morimoto, Toshitaka Nakamura, Takanori Komada, Chintogtokh Baatarjav, Yuma Saimoto, Yuka Jinnouchi, Kazuhisa Watanabe, Kouichi Miura, Naoya Yahagi, Kiyotaka Nakagawa, Takayoshi Matsumura, Ken-Ichi Yamada, Shun Ishibashi, Naohiro Sata, Marcus Conrad, Masafumi Takahashi
Recent evidence indicates ferroptosis is implicated in the pathophysiology of various liver diseases; however, the organ-specific regulation mechanism is poorly understood. Here, we demonstrate 7-dehydrocholesterol reductase (DHCR7), the terminal enzyme of cholesterol biosynthesis, as a regulator of ferroptosis in hepatocytes. Genetic and pharmacological inhibition (with AY9944) of DHCR7 suppress ferroptosis in human hepatocellular carcinoma Huh-7 cells. DHCR7 inhibition increases its substrate, 7-dehydrocholesterol (7-DHC)...
March 12, 2024: Nature Communications
#4
JOURNAL ARTICLE
Jingyuan Chen, Shuhao Fan, Jianhua Guo, Jian Yang, Le Pan, Yong Xia
Bladder cancer is a prevalent malignancy affecting the urinary system, which presents a significant global health concern. Although there are many treatments for bladder cancer, identifying more effective drugs and methods remains an urgent problem. As a pivotal component of contemporary medical practice, traditional Chinese medicine (TCM) assumes a crucial role in the realm of anti-tumor therapy, especially with the identification of active ingredients and successful exploration of pharmacological effects...
February 29, 2024: Toxicology and Applied Pharmacology
#5
JOURNAL ARTICLE
Yaxu Li, Qiao Ran, Qiuhui Duan, Jiali Jin, Yanjin Wang, Lei Yu, Chaojie Wang, Zhenyun Zhu, Xin Chen, Linjun Weng, Zan Li, Jia Wang, Qi Wu, Hui Wang, Hongling Tian, Sihui Song, Zezhi Shan, Qiwei Zhai, Huanlong Qin, Shili Chen, Lan Fang, Huiyong Yin, Hu Zhou, Xuejun Jiang, Ping Wang
Ferroptosis, a form of regulated cell death that is driven by iron-dependent phospholipid peroxidation, has been implicated in multiple diseases, including cancer1-3 , degenerative disorders4 and organ ischaemia-reperfusion injury (IRI)5,6 . Here, using genome-wide CRISPR-Cas9 screening, we identified that the enzymes involved in distal cholesterol biosynthesis have pivotal yet opposing roles in regulating ferroptosis through dictating the level of 7-dehydrocholesterol (7-DHC)-an intermediate metabolite of distal cholesterol biosynthesis that is synthesized by sterol C5-desaturase (SC5D) and metabolized by 7-DHC reductase (DHCR7) for cholesterol synthesis...
January 31, 2024: Nature
#6
JOURNAL ARTICLE
Florencio Porto Freitas, Hamed Alborzinia, Ancély Ferreira Dos Santos, Palina Nepachalovich, Lohans Pedrera, Omkar Zilka, Alex Inague, Corinna Klein, Nesrine Aroua, Kamini Kaushal, Bettina Kast, Svenja M Lorenz, Viktoria Kunz, Helene Nehring, Thamara N Xavier da Silva, Zhiyi Chen, Sena Atici, Sebastian G Doll, Emily L Schaefer, Ifedapo Ekpo, Werner Schmitz, Aline Horling, Peter Imming, Sayuri Miyamoto, Ann M Wehman, Thiago C Genaro-Mattos, Karoly Mirnics, Lokender Kumar, Judith Klein-Seetharaman, Svenja Meierjohann, Isabel Weigand, Matthias Kroiss, Georg W Bornkamm, Fernando Gomes, Luis Eduardo Soares Netto, Manjima B Sathian, David B Konrad, Douglas F Covey, Bernhard Michalke, Kurt Bommert, Ralf C Bargou, Ana Garcia-Saez, Derek A Pratt, Maria Fedorova, Andreas Trumpp, Marcus Conrad, José Pedro Friedmann Angeli
Ferroptosis is a form of cell death that has received considerable attention not only as a means to eradicate defined tumour entities but also because it provides unforeseen insights into the metabolic adaptation that tumours exploit to counteract phospholipid oxidation1,2 . Here, we identify proferroptotic activity of 7-dehydrocholesterol reductase (DHCR7) and an unexpected prosurvival function of its substrate, 7-dehydrocholesterol (7-DHC). Although previous studies suggested that high concentrations of 7-DHC are cytotoxic to developing neurons by favouring lipid peroxidation3 , we now show that 7-DHC accumulation confers a robust prosurvival function in cancer cells...
January 31, 2024: Nature
#7
JOURNAL ARTICLE
Zicheng Ma, Lei Guo, Mengjiao Pan, Chenlong Jiang, Depeng Liu, Yanni Gao, Juan Bai, Ping Jiang, Xing Liu
Pseudorabies virus (PRV) is an alpha-herpesvirus capable of infecting a range of animal species, particularly its natural host, pigs, resulting in substantial economic losses for the swine industry. Recent research has shed light on the significant role of cholesterol metabolism in the replication of various viruses. However, the specific role of cholesterol metabolism in PRV infection remains unknown. Here, we demonstrated that the expression of 7-dehydrocholesterol reductase (DHCR7) is upregulated following PRV infection, as evidenced by the proteomic analysis...
January 19, 2024: Veterinary Microbiology
#8
JOURNAL ARTICLE
Xinyu Mei, Jinfeng Xiong, Jian Liu, Anni Huang, Da Zhu, Yafei Huang, Hui Wang
Cervical cancer (CC) patients with lymph node metastasis (LNM) have a poor prognosis. However, the molecular mechanism of LNM in CC is unclear, and there is no effective clinical treatment. Here, we found that 7-dehydrocholesterol reductase (DHCR7), an enzyme that catalyzes the last step of cholesterol synthesis, was upregulated in CC and closely related to LNM. Gain-of-function and loss-of-function experiments proved that DHCR7 promoted the invasion ability of CC cells and lymphangiogenesis in vitro and induced LNM in vivo...
January 9, 2024: Cancer Letters
#9
JOURNAL ARTICLE
Nagham Nafiz Hendi, Georges Nemer
The short-chain dehydrogenase/reductase (SDR) superfamily encompasses enzymes that play essential roles in the metabolism of steroid hormones and lipids. Despite an enigmatic function, recent genetic studies have linked the novel SDR 42 extended-1 (SDR42E1) gene to 25-hydroxyvitamin D levels. This study investigated the potential SDR42E1 functions and interactions with vitamin D using bioinformatics and molecular docking studies. Phylogenetic analysis unveiled that the nucleotide sequences of human SDR42E1 exhibit high evolutionary conservation across nematodes and fruit flies...
December 29, 2023: Journal of Steroid Biochemistry and Molecular Biology
#10
JOURNAL ARTICLE
Zhibin Li, Tingting Hu, Ruiwen Li, Jinlan Li, Youli Wang, Yanyan Li, Yaqiu Lin, Yong Wang, Xing Jiani
Cholesterol is regarded as a signaling molecule in regulating the metabolism and function of fat cells, in which 7-Dehydrocholesterol reductase (DHCR7) is a key enzyme that catalyzes the conversion of 7-dehydrocholesterol to cholesterol, however, the exact function of DHCR7 in goat adipocytes remains unknown. Here, the effect of DHCR7 on the formation of subcutaneous and intramuscular fat in goats was investigated in vitro , and the result indicated that the mRNA level of DHCR7 showed a gradual downward trend in subcutaneous adipogenesis, but an opposite trend in intramuscular adipogenesis...
December 29, 2023: Animal Biotechnology
#11
JOURNAL ARTICLE
Yuanmin Dong, Jing Zhang, Yan Wang, Yulin Zhang, Daniella Rappaport, Zhenmei Yang, Maosen Han, Ying Liu, Zhipeng Fu, Xiaotian Zhao, Chunwei Tang, Chongdeng Shi, Daizhou Zhang, Dawei Li, Shilei Ni, Anning Li, Jiwei Cui, Tao Li, Peng Sun, Ofra Benny, Cai Zhang, Kun Zhao, Chen Chen, Xinyi Jiang
Glioblastoma multiforme (GBM) is notoriously resistant to immunotherapy due to its intricate tumor microenvironment (TME). Dysregulated cholesterol metabolism is implicated in the immunosuppressive TME and promotes tumor progression. Here, we found that cholesterol levels in GBM tissues are abnormally high, and glioma-supportive macrophages (GSMs), an essential "cholesterol factory", demonstrated aberrantly hyperactive cholesterol metabolism and efflux, providing cholesterol to fuel GBM growth and induce CD8+ T cells exhaustion...
December 21, 2023: Advanced Materials
#12
JOURNAL ARTICLE
Yuteng Ma, Zhe Wang, Jian Sun, Jingtong Tang, Jianping Zhou, Ming Dong
PURPOSE: Colon cancer is one of the leading causes of death worldwide, and screening of effective molecular markers for the diagnosis is prioritised for prevention and treatment. This study aimed to investigate the diagnostic and predictive potential of genes related to the lipid metabolism pathway, regulated by a protein called sterol-regulatory element-binding transcription Factor 2 (SREBF2), for colon cancer and patient outcomes. METHODS: We used machine-learning algorithms to identify key genes associated with SREBF2 in colon cancer based on a public database...
2023: OncoTargets and Therapy
#13
JOURNAL ARTICLE
Ellen R Elias, Lucas E Orth, Amy Li, Libin Xu, Sara M Jones, William B Rizzo
BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is an inherited disorder of cholesterol biosynthesis associated with congenital malformations, growth delay, intellectual disability and behavior problems. SLOS is caused by bi-allelic mutations in DHCR7 , which lead to reduced activity of 7-dehydrocholesterol reductase that catalyzes the last step in cholesterol biosynthesis. Symptoms of SLOS are thought to be due to cholesterol deficiency and accumulation of its precursor 7-dehydrocholesterol (7-DHC) and 8-dehydrocholesterol (8-DHC), and toxic oxysterols...
March 2024: Molecular Genetics and Metabolism Reports
#14
JOURNAL ARTICLE
Jingjing Huang, Huayang Pan, Jing Sun, Jiaming Wu, Qiyue Xuan, Jinge Wang, Shanjia Ke, Shounan Lu, Zihao Li, Zhigang Feng, Yongliang Hua, Qingan Yu, Bing Yin, Baolin Qian, Menghua Zhou, Yanan Xu, Miaoyu Bai, Yingmei Zhang, Yaohua Wu, Yong Ma, Hongchi Jiang, Wenjie Dai
BACKGROUND: The endoplasmic reticulum (ER) regulates critical processes, including lipid synthesis, which are affected by transmembrane proteins localized in the ER membrane. One such protein, transmembrane protein 147 (TMEM147), has recently been implicated for its role in hepatocellular carcinoma (HCC) tumorigenesis; however, the mechanisms remain unclear. We investigated the role of TMEM147 in HCC and the underlying mechanisms. METHODS: TMEM147 expression was examined in human HCC cells and adjacent non-tumorous tissues using quantitative reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry...
October 28, 2023: Journal of Experimental & Clinical Cancer Research: CR
#15
Amy Li, Libin Xu
Smith-Lemli-Opitz syndrome (SLOS) is a neurodevelopmental disorder caused by genetic mutations in the DHCR7 gene, encoding the enzyme 3β-hydroxysterol-Δ 7 -reductase (DHCR7) that catalyzes the last step of cholesterol synthesis. The resulting deficiency in cholesterol and accumulation of its precursor, 7-dehydrocholesterol (7-DHC), have a profound impact on brain development, which manifests as developmental delay, cognitive impairment, and behavioral deficits. To understand how the brain regions are differentially affected by the defective Dhcr7, we aim to map the regional distribution of sterols and other lipids in neonatal brains from a Dhcr7 -KO mouse model of SLOS, using mass spectrometry imaging (MSI)...
October 2, 2023: bioRxiv
#16
JOURNAL ARTICLE
Naoko Kuwabara, Shinji Sato, Saori Nakagawa
Dyslipidemia is a lifestyle-related (physical inactivity or obesity) disease; therefore, dietary foods that can easily be consumed in daily life is important to prevent dyslipidemia. Ergosterol, a precursor of vitamin D2 , is a fungal sterol present in the membranes of edible mushrooms and other fungi. Ergosterol is converted to brassicasterol by 7-dehydrocholesterol reductase (DHCR7), a cholesterol biosynthesis enzyme that converts 7-dehydrocholesterol (a precursor of vitamin D3 ) into cholesterol. Previously, we reported that ergosterol increases 7-dehydrocholesterol, decreases cholesterol levels by competitive effect of DHCR7, and reduces DHCR7 mRNA and protein levels in human HepG2 hepatoma cells...
September 30, 2023: Biological & Pharmaceutical Bulletin
#17
JOURNAL ARTICLE
Zeljka Korade, Allison Anderson, Marta Balog, Keri A Tallman, Ned A Porter, Karoly Mirnics
The concurrent use of several medications is a common practice in the treatment of complex psychiatric conditions. One such commonly used combination is aripiprazole (ARI), an antipsychotic, and trazodone (TRZ), an antidepressant. In addition to their effects on dopamine and serotonin systems, both of these compounds are inhibitors of the 7-dehydrocholesterol reductase (DHCR7) enzyme. To evaluate the systemic and nervous system distribution of ARI and TRZ and their effects on cholesterol biosynthesis, adult mice were treated with both ARI and TRZ for 21 days...
August 28, 2023: Biomolecules
#18
JOURNAL ARTICLE
Zengqi Zhao, Baolin Li, Qiang Chen, Xiaojun Xiang, Xiang Xu, Shangzhe Han, Wencong Lai, Yueru Li, Wei Xu, Kangsen Mai, Qinghui Ai
Sterol regulatory element-binding protein 2 (SREBP2) is considered to be a major regulator to control cholesterol homeostasis in mammals. However, the role of SREBP2 in teleost remains poorly understand. Here, we explored the molecular characterization of SREBP2 and identified SREBP2 as a key modulator for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and 7-dehydrocholesterol reductase (DHCR7) which were rate-limiting enzymes of cholesterol biosynthesis. Moreover, dietary palm oil (PO) in vivo or palmitic acid (PA) treatment in vitro elevated cholesterol content through triggering SREBP2-mediated cholesterol biosynthesis in large yellow croaker...
September 13, 2023: British Journal of Nutrition
#19
JOURNAL ARTICLE
Jacob T Beckley, Teresa K Aman, Michael A Ackley, Tatiana M Kazdoba, Michael C Lewis, Anne C Smith, Brandon J Farley, Jing Dai, Wayne Deats, Ethan Hoffmann, Albert J Robichaud, James J Doherty, Michael C Quirk
BACKGROUND AND PURPOSE: Select neuroactive steroids (NAS) tune neural activity by modulating excitatory and inhibitory neurotransmission, including the endogenous cholesterol metabolite 24(S)-hydroxycholesterol (24(S)-HC), which is a N-methyl-d-aspartate receptor (NMDAR) positive allosteric modulator (PAM). NMDAR PAMs are potentially an effective pharmacotherapeutic strategy to treat conditions associated with NMDAR hypofunction. EXPERIMENTAL APPROACHES: Using in vitro and in vivo electrophysiological recording experiments and behavioral approaches, we evaluated the effect of SAGE-718, a novel NAS NMDAR PAM currently in clinical development for the treatment of cognitive impairment, on NMDAR function and endpoints that are altered by NMDAR hypoactivity, and assessed its safety profile...
September 12, 2023: British Journal of Pharmacology
#20
JOURNAL ARTICLE
Ran Yuan, Wei Zhang, Yong-Ping You, Gang Cui, Zhengliang Gao, Xiuxing Wang, Jian Chen
Glioblastoma is one of the most common malignant brain tumors. Vitamin D, primarily its hormonally active form Calcitriol, has been reported to have anti-cancer activity. Here, we used patient-derived glioma cell lines to examine the effect of Vitamin D3 and Calcitriol on glioblastoma. Surprisingly, Vitamin D3 showed a more significant inhibitory effect than Calcitriol on cell viability and proliferation. Vitamin D receptor (VDR) mediates most of vitamin D's cellular effects, and thus we examined the expression level and function of VDR via gene silencing and gene knockout experiments...
July 25, 2023: FEBS Open Bio
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