Loss of long-chain acyl-CoA dehydrogenase protects against acute kidney injury.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος:	Loss of long-chain acyl-CoA dehydrogenase protects against acute kidney injury.
Συγγραφείς:	Chiba T, Oda A, Zhang Y, Bons J, Bharathi SS, Pfister KE, Zhang BB, Richert AC, Schilling B, Goetzman ES, Sims-Lucas S
Πηγή:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Oct 25. Date of Electronic Publication: 2024 Oct 25.
Τύπος έκδοσης:	Journal Article; Preprint
Γλώσσα:	English
Στοιχεία περιοδικού:	Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
Περίληψη:	Proximal tubular epithelial cells (PTECs) are particularly vulnerable to acute kidney injury (AKI). While fatty acids are the preferred energy source for PTECs via fatty acid oxidation (FAO), FAO-mediated H 2 O 2 production in mitochondria has been shown to be a major source of oxidative stress. We have previously shown that a mitochondrial flavoprotein, long-chain acyl-CoA dehydrogenase (LCAD), which catalyzes a key step in mitochondrial FAO, directly produces H 2 O 2 in vitro . Further we have established that loss of a lysine deacylase, Sirtuin 5 ( Sirt5 ^-/- ), induces hypersuccinylation and inhibition of mitochondrial FAO genes to stimulate peroxisomal FAO and to protect against AKI. However, the role of LCAD has yet to be determined. Mass spectrometry data acquisition revealed that LCAD is hypersuccinylated in Sirt5 ^-/- kidneys after AKI. Following two distinct models of AKI, cisplatin treatment or renal ischemia/reperfusion (IRI), LCAD knockout mice ( LCAD ^-/- ) demonstrated renoprotection against AKI. Specifically, LCAD ^-/- kidneys displayed mitigated renal tubular injury, decreased oxidative stress, preserved mitochondrial function, enhanced peroxisomal FAO, and decreased ferroptotic cell death. LCAD deficiency confers protection against two distinct models of AKI. This suggests a therapeutically attractive mechanism whereby preserved mitochondrial respiration as well as enhanced peroxisomal FAO by loss of LCAD mediates renoprotection against AKI.
Σχόλια:	Update in: JCI Insight. 2025 Feb 11;10(6):e186073. doi: 10.1172/jci.insight.186073.. (PMID: 39932791)
Grant Information:	S10 OD028654 United States OD NIH HHS
Entry Date(s):	Date Created: 20241101 Latest Revision: 20250324
Update Code:	20260130
PubMed Central ID:	PMC11526992
DOI:	10.1101/2024.10.22.619640
PMID:	39484612
Βάση Δεδομένων:	MEDLINE

Full Text Finder

καταχωρήστε σχόλιο πρώτοι!