PXD054079-1

PXD054079 is an original dataset announced via ProteomeXchange.

Title	Regression of Post-Prandial Cardiac Hypertrophy in Burmese Pythons is Mediated by FoxO1
Description	As ambush-hunting predators that consume large prey after long intervals of fasting, Burmese pythons evolved with unique adaptations for regulating organ structure and function. Among these is cardiac hypertrophy that develops within three days following a meal (1, 2), which we previously showed was initiated by circulating growth factors (3). Post-prandial cardiac hypertrophy in pythons also rapidly regresses with subsequent fasting (2); however, the molecular mechanisms that regulate the dynamic cardiac remodeling in pythons during digestion are largely unknown. In this study, we employed a multi-omics approach coupled with targeted molecular analyses to examine remodeling of the python ventricular transcriptome and proteome throughout digestion. We found that forkhead box protein O1 (FoxO1) signaling was suppressed prior to hypertrophy development and then activated with regression, which coincided with decreased and then increased expression, respectively, of FoxO1 transcriptional targets involved in protein degradation. To define the molecular mechanistic role of FoxO1 in hypertrophy regression, we used cultured mammalian cardiomyocytes treated with post-fed python plasma. Hypertrophy regression both in pythons and in vitro coincided with activation of FoxO1-dependent autophagy; however, introduction of a FoxO1-specific inhibitor prevented both regression of cell size and autophagy activation. Finally, to determine if FoxO1 activation could induce regression, we generated an adenovirus expressing a constitutively active FoxO1. FoxO1 activation was sufficient to prevent and reverse post-fed plasma-induced hypertrophy, which was partially prevented by autophagy inhibition. Our results indicate that modulation of FoxO1 activity contributes to the dynamic ventricular remodeling in post-prandial Burmese pythons.
HostingRepository	PRIDE
AnnounceDate	2024-09-12
AnnouncementXML	Submission_2024-09-11_21:08:07.163.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD054079
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Thomas Martin
SpeciesList	scientific name: Python bivittatus; NCBI TaxID: 176946;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-20 14:15:09	ID requested
⏵ 1	2024-09-11 21:08:07	announced

10.6019/PXD054079;

submitter keyword: cardiac hypertrophy, autophagy, FoxO1,Burmese python, hypertrophy regression

Leslie Leinwand
contact affiliation	University of Colorado Boulder BioFrontiers MCDB
contact email	leslie.leinwand@colorado.edu
lab head
Thomas Martin
contact affiliation	University of Colorado Boulder
contact email	thomas.martin-2@colorado.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD054079
     1. Label: PRIDE project
     2. Name: Regression of Post-Prandial Cardiac Hypertrophy in Burmese Pythons is Mediated by FoxO1