Overexpression of cysteine sulfinic acid decarboxylase stimulated by hepatocarcinogenesis results in autoantibody production in rats

Kishimoto, T; Kokura, Kenji; Nakadai, Tomoyoshi; Miyazawa, Y; Wakamatsu, Toshio; Makino, Yuko; Nakamura, Takashi; Hara, Eiko; Oda, Kazuhiro; Muramatsu, M

doi:10.1016/s0928-4346(97)89835-0

Cited by 7 publications

(9 citation statements)

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“…The overexpression of other targets like CSAD and reduced expression of Proliferation associated protein 2G4 (PA2G4), Nitrilase, Annexin A6, N‐myc downstream‐regulated gene 2 Protein (NDRG2), Tyrosine 3‐monooxygenase/tryptophan 5‐monooxygenase activation protein/epsilon polypeptide, Methylcrotonyl CoA carboxylase (MCC), Catechol‐O‐methyl transferase (COMT) are in good agreement with previous data. However, the involvement of Cytochrome C oxidase, Alpha‐aminoadipic semialdehyde dehydrogenase, IDO and Arsenite methyl transferase in HCC has not been well documented.…”

Section: Discussionsupporting

confidence: 89%

Defects in long‐chain 3‐hydroxy acyl‐CoA dehydrogenase lead to hepatocellular carcinoma: A novel etiology of hepatocellular carcinoma

Khare

Angdisen

et al. 2020

Intl Journal of Cancer

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The incidence of both nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) have been increasing at an alarming rate. Little is known about NAFLD without cirrhosis as a risk for HCC. Here we report, for the first time, generation of a mouse model with a defect in long-chain 3-hydoxy acyl-CoA dehydrogenase (LCHAD). The LCHAD exon 15 deletion was embryonic lethal to the homozygous mice whereas heterozygous mice (HT) develop significant hepatic steatosis starting at young age (3 months old) and HCC at older age (>13 months old) without any evidence of fibrosis or cirrhosis. None of the wild-type (WT) mice developed steatosis and HCC (n = 39), whereas HT-LCHAD mice (n = 41) showed steatosis and~20% (8/41) developed liver masses with histological features of HCC. Proteomic analysis of liver tissues from WT-mice and HT-mice with no signs of HCC was conducted. Proteins with significant changes in abundance were identified by mass spectrometry. Abundance of 24 proteins was significantly different (p < 0.01) between WT and HT-LCHAD mice. The proteins found to vary in abundance are associated with different cellular response processes ranging from intermediary metabolism of carbohydrate, protein and lipid to oxidative stress, signal transduction and the process of tumorigenesis. Protein expression pattern of the HT-LCHAD mouse liver indicates predisposition to HCC and suggests that impaired hepatic mitochondrial fatty acid oxidation plays an important role in the development and progression of HCC. To assess the implication of these studies in human disease, we demonstrated significant downregulation of HADHA transcripts in HCC patients.

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Section: Discussionsupporting

confidence: 89%

Defects in long‐chain 3‐hydroxy acyl‐CoA dehydrogenase lead to hepatocellular carcinoma: A novel etiology of hepatocellular carcinoma

Khare

Angdisen

et al. 2020

Intl Journal of Cancer

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“…Therefore, the lack of anti-Id, and not the presence of GAD-Abs per se, leads to the onset of GAD-Abs related diseases. Some experimental data [6] demonstrated a relationship between HCC and high expression of cysteine sulfinic acid decarboxylase, an enzyme having significant structural and functional similarities with GAD, leading to the production of GAD-Abs. In our case we could hypothesize an imbalance between anti-Id and GAD-Abs, with an overproduction of the latter ones by the HCC.…”

Section: Discussionmentioning

confidence: 99%

Clinico-pathological findings in a patient with progressive cerebellar ataxia, autoimmune polyendocrine syndrome, hepatocellular carcinoma and anti-GAD autoantibodies

Piccolo

Cavallaro

Romani

et al. 2010

Journal of the Neurological Sciences

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“…The functions of 28 genes intensively up-regulated (>3-fold) in only AhR+/+ mice compared with AhR-/-knockout mice were associated with maintenance and stabilization of spermatozoa mitochondria (Mcsp) [1], cell proliferation and transformation related with carcinogenesis (Myc) [14,17], stress response (Hspa2, Atf3, Plcb2) [2,11], chemotaxis (S100a8) [35], inflammatory response (Ngp, Saa2, S100a8, S100a9, Cyp4f16, Tnfrsf1b, Csf2rb2, Plcb2) [6,34,35], acute-phase r e s p o n s e ( S a a 2 ) [ 3 4 ] a n d i m m u n e r e s p o n s e (Adamdec1,Csf2rb2, Cdgap, H2-D1) [3,41], cell adhesion (Cml5) [25], neuronal excitation (Kcnq2) [8], cell division (Meig1) [33]. Meanwhile, the functions of 23 genes intensively down-regulated (>3-fold) in only AhR+/+ mice were associated with cell metabolism (Slc13a2, Afmid, Csad, 1810073K19Rik, E130112L23Rik, Upk3b) [16,19,23,30], nerve regeneration (Vamp1) [5], cell growth (Tieg1, Erbb2ip, Ngfa) [21,22], cell cycle (Cdc20) [32], testis-specific Ca 2+ -binding protein (Cabyr) [29] and inhibition of tumor growth (Lect1) [12]. The results reported here suggest that toxicity may reflect sustained alterations in the expression of many genes and that the changes reflect both direct and indirect effects of µg/kg body weight were not only the genes encoding drug metabolizing enzymes and stress response genes but also a wide variety of genes encoding cytoskeleton related proteins, signal transduction, and plasma proteins [18].…”

Section: Discussionmentioning

confidence: 99%

Gene Expression profile by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in the Liver of Wild-Type (AhR+/+) and Aryl Hydrocarbon Receptor-Deficient (AhR-/-) Mice

Yoon¹,

Park²,

Kim³

et al. 2006

The Journal of Veterinary Medical Science

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ABSTRACT. 2,3,7, is one of the most toxic environmental pollutants that cause various biological effects on mammals. The purpose of our study was to identify the genes involved in hepatotoxicity and hepatocarcinogenesis caused by TCDD. C57BL/6 (AhR+/+, wild type) and B6.129-AhR/J (AhR-/-, knock out) mice were injected i.p. with a single treatment of TCDD at the dose of 100 µg/kg body weight. Relative liver weight was significantly increased at 72 hr after TCDD treatment without an apparent histopathological change in AhR+/+ mice (p<0.05). TCDD treatment also significantly increased activity of serum alanine aminotransferase in AhR-/-mice (p<0.05). The liver was analyzed for gene expression profiles 72 hr later. As compared with AhR-/-mice, the expression of 51 genes (>3-fold) was changed in AhR+/+ mice; 28 genes were induced, while 23 genes were repressed. Most of the genes were associated with chemotaxis, inflammation, carcinogenesis, acute-phase response, immune responses, cell metabolism, cell proliferation, signal transduction, and tumor suppression. This study suggests that the microarray analysis of genes in the liver of AhR+/+ and AhR-/-mice may help to clarify the mechanism of AhR-mediated hepatotoxicity and hepatocarcinogenesis by TCDD.

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Overexpression of cysteine sulfinic acid decarboxylase stimulated by hepatocarcinogenesis results in autoantibody production in rats

Cited by 7 publications

References 0 publications

Defects in long‐chain 3‐hydroxy acyl‐CoA dehydrogenase lead to hepatocellular carcinoma: A novel etiology of hepatocellular carcinoma

Defects in long‐chain 3‐hydroxy acyl‐CoA dehydrogenase lead to hepatocellular carcinoma: A novel etiology of hepatocellular carcinoma

Clinico-pathological findings in a patient with progressive cerebellar ataxia, autoimmune polyendocrine syndrome, hepatocellular carcinoma and anti-GAD autoantibodies

Gene Expression profile by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in the Liver of Wild-Type (AhR+/+) and Aryl Hydrocarbon Receptor-Deficient (AhR-/-) Mice

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