Role of cellular retinol‐binding protein, type 1 and retinoid homeostasis in the adult mouse heart: A multi‐omic approach. Issue 4 (6th March 2022)

• Record Type: Journal Article
• Authors: Zalesak‐Kravec, Stephanie; Huang, Weiliang; Jones, Jace W.; Yu, Jianshi; Alloush, Jenna; Defnet, Amy E.; Moise, Alexander R.; Kane, Maureen A.
• Is Part Of: FASEB journal. Volume 36:Issue 4(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-03-06
• Subjects: cellular retinol‐binding protein, type 1 -- heart -- mice -- retinoic acid -- retinoid metabolism; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202100901RRR
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: The main active metabolite of Vitamin A, all ‐ trans retinoic acid (RA), is required for proper cellular function and tissue organization. Heart development has a well‐defined requirement for RA, but there is limited research on the role of RA in the adult heart. Homeostasis of RA includes regulation of membrane receptors, chaperones, enzymes, and nuclear receptors. Cellular retinol‐binding protein, type 1 (CRBP1), encoded by retinol‐binding protein, type 1 ( Rbp1 ), regulates RA homeostasis by delivering vitamin A to enzymes for RA synthesis and protecting it from non‐specific oxidation. In this work, a multi‐omics approach was used to characterize the effect of CRBP1 loss using the Rbp1 −/− mouse. Retinoid homeostasis was disrupted in Rbp1 −/− mouse heart tissue, as seen by a 33% and 24% decrease in RA levels in the left and right ventricles, respectively, compared to wild‐type mice (WT). To further inform on the effect of disrupted RA homeostasis, we conducted high‐throughput targeted metabolomics. A total of 222 metabolite and metabolite combinations were analyzed, with 33 having differential abundance between Rbp1 −/− and WT hearts. Additionally, we performed global proteome profiling to further characterize the impact of CRBP1 loss in adult mouse hearts. More than 2606 unique proteins were identified, with 340 proteins having differential expression between Rbp1 −/− and WT hearts. Pathway analysis performed on metabolomic and proteomic data revealed pathways related to cellular metabolism and cardiac metabolism were the most disrupted in Rbp1 −/− mice. Together, these studies characterize the effect of CRBP1 loss and reduced RA in the adult heart.