Cardioprotective Potential of Exogenous Ubiquitin
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INVITED REVIEW ARTICLE
Cardioprotective Potential of Exogenous Ubiquitin Suman Dalal 1,2 & Paige L. Shook 1 & Mahipal Singh 1 & Krishna Singh 1,2,3 Accepted: 17 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Ischemic heart disease (IHD) accounts for the majority of heart disease-related deaths worldwide. Ubiquitin (UB), found in all eukaryotic cells, is a highly conserved low molecular weight (~8.5 kDa) protein. A well-known intracellular function of UB is to regulate protein turnover via the UB-proteasome system. UB is a normal constituent of plasma, and elevated levels of UB are observed in the serum of patients under a variety of pathological conditions. Recent studies provide evidence for cardioprotective potential of exogenous UB in the remodeling process of the heart in IHD, including effects on cardiac myocyte apoptosis, inflammatory response, and reorganization of the vasculature and extracellular matrix. This review summarizes functions of UB with an emphasis on the role of exogenous UB in myocardial remodeling in IHD. Keywords Ubiquitin . Heart . Myocardial remodeling . Apoptosis . Fibrosis
Introduction Heart failure represents a major cause of morbidity and mortality worldwide. Ischemic heart disease (IHD), also known as coronary artery disease, accounts for majority of deaths related to heart failure [1, 2]. Ubiquitin (UB), a highly conserved protein with a molecular weight of ~8.5 kDa, is found in all eukaryotic cells. The most important intracellular function of UB is to regulate protein turnover via the UB-proteasome system (UPS) [3]. UB is a normal constituent of plasma. Elevated levels of UB are observed in the serum or plasma of patients with a variety of pathological conditions. Based on few reports, extracellular UB is proposed to have pleiotropic functions [4, 5]. Recent work provides evidence for a cardioprotective role of exogenous UB with respect to remodeling processes of the heart, specifically related to myocyte apoptosis, inflammation, angiogenesis, fibrosis, and cardiac
* Krishna Singh [email protected] 1
Department of Biomedical Sciences, James H Quillen College of Medicine, East Tennessee State University, PO Box 70582, Johnson City, TN 37614, USA
2
Center of Excellence for Inflammation, Infectious Disease and Immunity, East Tennessee State University, Johnson City, TN 37614, USA
3
James H Quillen Veterans Affairs Medical Center, Mountain Home, TN 37684, USA
function. Therefore, the main objective of this review article is to summarize the functions of UB with a particular emphasis on the potential cardioprotective effects of exogenous UB in remodeling process of the heart in IHD. UB and Its Intracellular Function UB protein consists of 76 amino acids. It was initially isolated and purified from bovine thymus in 1975. Due to its widespread presence in living cells, it was originally named as ubiquitous immunopoietic polypeptide (UBIP) [6]. UB consists of seven lysine residues with no cysteine and tryptophan residues [4]. The lysine resi
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