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ACBP/DBI protein ne...
ACBP/DBI protein neutralization confers autophagy-dependent organ protection through inhibition of cell loss, inflammation, and fibrosis
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Motiño, O (author)
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Lambertucci, F (author)
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Anagnostopoulos, G (author)
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Li, S (author)
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Nah, J (author)
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Castoldi, F (author)
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Senovilla, L (author)
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Montégut, L (author)
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Chen, H (author)
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Durand, S (author)
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Bourgin, M (author)
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Aprahamian, F (author)
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Nirmalathasan, N (author)
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Alvarez-Valadez, K (author)
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Sauvat, A (author)
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Carbonnier, V (author)
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Djavaheri-Mergny, M (author)
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- Pietrocola, F (author)
- Karolinska Institutet
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Sadoshima, J (author)
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Maiuri, MC (author)
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Martins, I (author)
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Kroemer, G (author)
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(creator_code:org_t)
- 2022-10-03
- 2022
- English.
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:41, s. e2207344119-
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Abstract
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- Acyl-coenzyme A (CoA)–binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), is an extracellular feedback regulator of autophagy. Here, we report that injection of a monoclonal antibody neutralizing ACBP/DBI (α-DBI) protects the murine liver against ischemia/reperfusion damage, intoxication by acetaminophen and concanavalin A, and nonalcoholic steatohepatitis caused by methionine/choline-deficient diet as well as against liver fibrosis induced by bile duct ligation or carbon tetrachloride. α-DBI downregulated proinflammatory and profibrotic genes and upregulated antioxidant defenses and fatty acid oxidation in the liver. The hepatoprotective effects of α-DBI were mimicked by the induction of ACBP/DBI-specific autoantibodies, an inducibleAcbp/Dbiknockout or a constitutiveGabrg2F77Imutation that abolishes ACBP/DBI binding to the GABAAreceptor. Liver-protective α-DBI effects were lost when autophagy was pharmacologically blocked or genetically inhibited by knockout ofAtg4b. Of note, α-DBI also reduced myocardium infarction and lung fibrosis, supporting the contention that it mediates broad organ-protective effects against multiple insults.
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- art (subject category)
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- By the author/editor
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Motiño, O
-
Lambertucci, F
-
Anagnostopoulos, ...
-
Li, S
-
Nah, J
-
Castoldi, F
-
show more...
-
Senovilla, L
-
Montégut, L
-
Chen, H
-
Durand, S
-
Bourgin, M
-
Aprahamian, F
-
Nirmalathasan, N
-
Alvarez-Valadez, ...
-
Sauvat, A
-
Carbonnier, V
-
Djavaheri-Mergny ...
-
Pietrocola, F
-
Sadoshima, J
-
Maiuri, MC
-
Martins, I
-
Kroemer, G
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show less...
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Proceedings of t ...
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Proceedings of t ...
- By the university
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Karolinska Institutet