Site‐specific cleavage of acetoacetyl‐CoA synthetase by legumain

Hasegawa, Shinya; Inoue, Dai; Yamasaki, Masahiro; Li, Chuan; Imai, Masahiko; Takahashi, Noriko; Fukui, Tetsuya

doi:10.1002/1873-3468.12197

Cited by 5 publications

(3 citation statements)

References 32 publications

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“…AACS has the ability to use ketone bodies for the creation of cholesterol and fatty acids, converting acetoacetate into its CoA ester to generate acetoacetyl-CoA in the cytosol [108]. This process is facilitated by HMGCS, which transforms acetoacetyl-CoA into 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) [109,110]. Subsequently, HMGCRa is able to facilitate the transformation of HMG-CoA into mevalonic acid in order to generate cholesterol [111].…”

Section: Discussionmentioning

confidence: 99%

High Starch Induces Hematological Variations, Metabolic Changes, Oxidative Stress, Inflammatory Responses, and Histopathological Lesions in Largemouth Bass (Micropterus salmoides)

Xie,

Shao,

Zhang

et al. 2024

Metabolites

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This study evaluated effects of high starch (20%) on hematological variations, glucose and lipid metabolism, antioxidant ability, inflammatory responses, and histopathological lesions in largemouth bass. Results showed hepatic crude lipid and triacylglycerol (TAG) contents were notably increased in fish fed high starch. High starch could increase counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils and serum contents of TAG, TBA, BUN, and LEP (p < 0.05). There were increasing trends in levels of GLUT2, glycolysis, gluconeogenesis, and LDH in fish fed high starch through the AKT/PI3K signal pathway. Meanwhile, high starch not only triggered TAG and cholesterol synthesis, but mediated cholesterol accumulation by reducing ABCG5, ABCG8, and NPC1L1. Significant increases in lipid droplets and vacuolization were also shown in hepatocytes of D3–D7 groups fed high starch. In addition, high starch could decrease levels of mitochondrial Trx2, TrxR2, and Prx3, while increasing ROS contents. Moreover, high starch could notably increase amounts of inflammatory factors (IL-1β, TNF-α, etc.) by activating NLRP3 inflammasome key molecules (GSDME, caspase 1, etc.). In conclusion, high starch could not only induce metabolic disorders via gluconeogenesis and accumulation of glycogen, TAG, and cholesterol, but could disturb redox homeostasis and cause inflammatory responses by activating the NLRP3 inflammasome in largemouth bass.

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Section: Discussionmentioning

confidence: 99%

High Starch Induces Hematological Variations, Metabolic Changes, Oxidative Stress, Inflammatory Responses, and Histopathological Lesions in Largemouth Bass (Micropterus salmoides)

Xie,

Shao,

Zhang

et al. 2024

Metabolites

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“…Whereas, for the moment, little knowledge of ACSF family in cancer has been reported until now. Hasegawa et al [ 15 , 16 ] demonstrate that the limited proteolysis of AACS can encode the ketone body-utilizing enzyme, and is adjusted transcriptionally by SREBP-2. Meanwhile, the ketone body metabolism regulated by AACS plays a significant role in cholesterol metabolism.…”

Section: Discussionmentioning

confidence: 99%

Identification of ACSF gene family as therapeutic targets and immune-associated biomarkers in hepatocellular carcinoma

Zhao

Liu

et al. 2022

Aging

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Acyl-CoA synthetases (ACSs) are responsible for acyl-CoA synthesis from nonpolar hydrophilic fatty acids and play a vital role in many metabolic processes. As a category of ACS isozymes, members of ACS family (AACS, ACSF2-3, AASDH) participate in lipid metabolism; however, their expression patterns, regulatory mechanisms and effects in hepatocellular carcinoma (HCC) are poorly understood. Here, through evaluating the expression profiles of ACSF gene family, we found that upregulated AACS might be more significant and valuable in development and progression of HCC. Consequently, the mRNA expression levels of AACS and ACSF2 was accordantly increased in HCC. Kaplan-Meier plotter revealed that HCC patients with high level of AACS were highly related to a shorter overall survival time and relapse-free survival. Genetic alterations using cBioPortal revealed that the alteration rate of AACS were 5%. We also found that the functions of ACSF gene family were linked to several cancer-associated pathways, including long-term potentiation, phospholipase D signaling pathway and purine metabolism. TIMER database indicated that the AACS and ACSF2 had a strong relationship with the infiltration of six types of immune cells (macrophages, neutrophils, CD8+ T-cells, B-cells, CD4+ T-cells and dendritic cells). Next, Diseasemeth database revealed that the global methylation levels of ACSF2 was higher in HCC patients. In conclusion, this study firstly demonstrated that Acyl-CoA synthesis gene family, in particular, AACS, could be associated with immune microenvironment, thereby influencing the development and prognosis of patients with HCC.

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“…After 2 days of transfection, the cells were harvested in cell lysis buffer (10 mM Tris-HCl pH7.4, 1% NP40, 150 mM NaCl, and 0.5 mM EDTA). AACS activity in 50 μg of protein extracts was assayed by measuring acetyl-CoA formation according to a method previously reported by Hasegawa et al 14…”

Section: Aacs Variant Functional Analysismentioning

confidence: 99%

Prospective cohort study for identification of underlying genetic causes in neonatal encephalopathy using whole-exome sequencing

Bruun

Desroches

Wilson

et al. 2018

Genetics in Medicine

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PurposeNeonatal encephalopathy, which is characterized by a decreased level of consciousness, occurs in 1-7/1,000 live-term births. In more than half of term newborns, there is no identifiable etiological factor. To identify underlying genetic defects, we applied whole-exome sequencing (WES) in term newborns with neonatal encephalopathy as a prospective cohort study.MethodsTerm newborns with neonatal encephalopathy and no history of perinatal asphyxia were included. WES was performed using patient and both parents' DNA.ResultsNineteen patients fulfilling inclusion criteria were enrolled. Five patients were excluded owing to withdrawal of consent, no parental DNA samples, or a genetic diagnosis prior to WES. Fourteen patients underwent WES. We confirmed a genetic diagnosis in five patients (36%): epileptic encephalopathy associated with autosomal dominant de novo variants in SCN2A (p.Met1545Val), KCNQ2 (p.Asp212Tyr), and GNAO1 (p.Gly40Arg); lipoic acid synthetase deficiency due to compound heterozygous variants in LIAS (p.Ala253Pro and p.His236Gln); and encephalopathy associated with an X-linked variant in CUL4B (p.Asn211Ser).ConclusionWES is helpful at arriving genetic diagnoses in neonatal encephalopathy and/or seizures and brain damage. It will increase our understanding and probably enable us to develop targeted neuroprotective treatment strategies.

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Site‐specific cleavage of acetoacetyl‐CoA synthetase by legumain

Cited by 5 publications

References 32 publications

High Starch Induces Hematological Variations, Metabolic Changes, Oxidative Stress, Inflammatory Responses, and Histopathological Lesions in Largemouth Bass (Micropterus salmoides)

High Starch Induces Hematological Variations, Metabolic Changes, Oxidative Stress, Inflammatory Responses, and Histopathological Lesions in Largemouth Bass (Micropterus salmoides)

Identification of ACSF gene family as therapeutic targets and immune-associated biomarkers in hepatocellular carcinoma

Prospective cohort study for identification of underlying genetic causes in neonatal encephalopathy using whole-exome sequencing

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