PXD075159-1

PXD075159 is an original dataset announced via ProteomeXchange.

Title	The Carnosine–HNE Michael Adduct as a Redox-Active Species Associated with Nrf2-Dependent Antioxidant and An-ti-Inflammatory Responses
Description	Carnosine (CAR), an endogenous histidine-containing dipeptide, exhibits antioxidant and anti-inflammatory activity in various experimental models; however, its molecular mechanism of action remains poorly understood. Here, we demonstrate that the Michael adduct between CAR and 4-hydroxy-2-nonenal (HNE), which has been detected in previ-ous studies in both in vitro and in vivo settings, mediates its bioactivity, particularly anti-oxidant and anti-inflammatory responses through Nrf2 activation. CAR-HNE adduct was synthesized and its physicochemical, metabolic, and biological properties were evaluated. CAR-HNE exhibited high stability in biological matrices and retained the ability to trans-fer HNE to thiol nucleophiles at a slow rate under physiologically relevant conditions, consistent with electrophile-mediated Nrf2 activation. This kinetic behavior limits the cy-totoxicity typically associated with free HNE while preserving redox signaling capacity. CAR-HNE induced dose-dependent Nrf2 activation and NF-κB inhibition in cell-based assays without the hormetic toxicity observed for free HNE. Mechanistically, CAR-HNE may act as a redox-tunable electrophilic reservoir, restoring nucleophilic tone and modu-lating redox-sensitive transcription factors. In vivo, CAR-HNE attenuated DSS-induced colitis more effectively than equimolar doses of either carnosine or HNE alone. Proteomic analyses revealed modulation of canonical Nrf2-dependent antioxidant pathways. Our findings suggest a conceptual shift in carnosine biology: rather than acting as a classical antioxidant or carbonyl quencher, carnosine functions as a precursor of redox-active elec-trophilic adducts that transduce anti-inflammatory and antioxidant responses via con-trolled RCS signaling.
HostingRepository	PRIDE
AnnounceDate	2026-04-06
AnnouncementXML	Submission_2026-04-05_16:11:01.589.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alessandra Altomare
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-03 12:01:00	ID requested
⏵ 1	2026-04-05 16:11:02	announced

Altomare A, Baron G, Gado F, Vedova LD, Ferrario G, Davani L, Gilardoni E, Ferrisi R, Mocchetti C, Singh L, Courten B, Carini M, Siracusa R, D'Amico R, Di Paola R, Dallanoce C, Impellizzeri D, Aldini G, The Carnosine-HNE Michael Adduct as a Redox-Active Species Associated with Nrf2-Dependent Antioxidant and Anti-Inflammatory Responses. Antioxidants (Basel), 15(3):(2026) [pubmed]

10.3390/antiox15030388;

submitter keyword: carnosine

4-hydroxy-2-nonenal (HNE)

Nrf2 activation

NF-κB

anti-inflammatory

anti-oxidant.

Alessandra Altomare
contact affiliation	University of MIlan - Department of Pharmaceutical Sciences
contact email	alessandra.altomare@unimi.it
lab head
Alessandra Altomare
contact affiliation	University of Milan (DISFARM)
contact email	alessandra.altomare@unimi.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD075159
     1. Label: PRIDE project
     2. Name: The Carnosine–HNE Michael Adduct as a Redox-Active Species Associated with Nrf2-Dependent Antioxidant and An-ti-Inflammatory Responses