Roles of SUMOylation in Heart Development and Cardiovascular Diseases

Zhang, L.; Yang, Tzu-Yi; Li, D. W.-C.

doi:10.2174/1566524016666161223110407

Cited by 12 publications

(7 citation statements)

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“…Next, we examined the ability of GA in restoring Sp1 activity in cells overexpressing Sumo1. This experiment was intended to provide evidence related to the potential use of GA to reduce the effects of Sumoylation-mediated aberrant signaling responsible for pathobiology of cells and tissues [ 45 , 47 , 49 , 50 , 51 , 52 , 53 ]. mLECs were transfected with WT-Prdx6 promoter along with GFP-Vector or GFP-Sumo1 plasmid, and then treated with different concentrations of GA ( Figure 10 D) and BA ( Figure 10 E).…”

Section: Resultsmentioning

confidence: 99%

Ginkgolic Acid Rescues Lens Epithelial Cells from Injury Caused by Redox Regulated-Aberrant Sumoylation Signaling by Reviving Prdx6 and Sp1 Expression and Activities

Chhunchha

Singh

et al. 2018

IJMS

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Sumoylation is a downstream effector of aging/oxidative stress; excess oxidative stress leads to dysregulation of a specificity protein1 (Sp1) and its target genes, such as Peroxiredoxin 6 (Prdx6), resulting in cellular damage. To cope with oxidative stress, cells rely on a signaling pathway involving redox-sensitive genes. Herein, we examined the therapeutic efficacy of the small molecule Ginkgolic acid (GA), a Sumoylation antagonist, to disrupt aberrant Sumoylation signaling in human and mouse lens epithelial cells (LECs) facing oxidative stress or aberrantly expressing Sumo1 (small ubiquitin-like modifier). We found that GA globally reduced aberrant Sumoylation of proteins. In contrast, Betulinic acid (BA), a Sumoylation agonist, augmented the process. GA increased Sp1 and Prdx6 expression by disrupting the Sumoylation signaling, while BA repressed the expression of both molecules. In vitro DNA binding, transactivation, Sumoylation and expression assays revealed that GA enhanced Sp1 binding to GC-boxes in the Prdx6 promoter and upregulated its transcription. Cell viability and intracellular redox status assays showed that LECs pretreated with GA gained resistance against oxidative stress-driven aberrant Sumoylation signaling. Overall, our study revealed an unprecedented role for GA in LECs and provided new mechanistic insights into the use of GA in rescuing LECs from aging/oxidative stress-evoked dysregulation of Sp1/Prdx6 protective molecules.

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Section: Resultsmentioning

confidence: 99%

Ginkgolic Acid Rescues Lens Epithelial Cells from Injury Caused by Redox Regulated-Aberrant Sumoylation Signaling by Reviving Prdx6 and Sp1 Expression and Activities

Chhunchha

Singh

et al. 2018

IJMS

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“…This pathway is important for post-translational modification of genes important for post-testicular sperm maturation and reproduction ( 55 ). It is also crucial for regulation of genes involved in cell survival and proliferation in the heart tissue ( 56 ). Several nervous system-associated proteins are modified by SUMOylation for its proper functioning and hence is a crucial process in a wide range of neurological and neurodegenerative diseases ( 57 ).…”

Section: Resultsmentioning

confidence: 99%

OUP accepted manuscript

Joseph

Mahale

2021

Database

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Male infertility is a multifactorial condition that contributes to around one-third of cases of infertility worldwide. Several chromosomal aberrations, single-gene and polygenic associations with male factor defects have been reported. These defects manifest as sperm number or sperm quality defects leading to infertility. However, in almost 40% of cases, the genetic etiology of male infertility remains unexplained. Understanding the causal genetic factors is crucial for effective patient management and counseling. Integrating the vast amount of available omics data on male infertility is a first step towards understanding, delineating and prioritizing genes associated with the different male reproductive disorders. The Male Infertility Knowledgebase (MIK) is a manually curated repository developed to boost research on the elusive genetic etiology of male infertility. It integrates information on ∼17 000 genes, their associated pathways, gene ontology, diseases and gene and sequence-based analysis tools. In addition, it also incorporates information on reported chromosomal aberrations and syndromic associations with male infertility. Disease enrichment of genes in MIK indicate a shared genetic etiology between cancer, male and female infertility disorders. While the genes involved in cancer pathways were found to be common causal factors for sperm number and sperm quality defects, the interleukin pathways were found to be shared and enriched between male factor defects and non-reproductive conditions like cardiovascular diseases, metabolic diseases, etc. Disease information in MIK can be explored further to identify high-risk conditions associated with male infertility and delineate shared genetic etiology. Utility of the knowledgebase in predicting novel genes is illustrated by identification of 149 novel candidates for cryptorchidism using gene prioritization and network analysis. MIK will serve as a platform for review of genetic information on male infertility, identification pleiotropic genes, prediction of novel candidate genes for the different male infertility diseases and for portending future high-risk diseases associated with male infertility. Database URL : http://mik.bicnirrh.res.in/

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“…Acute cardiac hypoxia induces elevated late sodium current and action potential prolongation in the heart and causes pro-arrhythmic change by SUMOylation of Nav1.5 channels [ 148 ]. In the decades since its discovery, studies related to SUMOylation in a variety of diseases have been extensively reported, including cardiovascular development and function [ 29 , 30 ].…”

Section: Concluding Remarks and Perspectivementioning

confidence: 99%

The Function of SUMOylation and Its Critical Roles in Cardiovascular Diseases and Potential Clinical Implications

Chen

et al. 2021

IJMS

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Cardiovascular disease (CVD) is a common disease caused by many factors, including atherosclerosis, congenital heart disease, heart failure, and ischemic cardiomyopathy. CVD has been regarded as one of the most common diseases and has a severe impact on the life quality of patients. The main features of CVD include high morbidity and mortality, which seriously threaten human health. SUMO proteins covalently conjugate lysine residues with a large number of substrate proteins, and SUMOylation regulates the function of target proteins and participates in cellular activities. Under certain pathological conditions, SUMOylation of proteins related to cardiovascular development and function are greatly changed. Numerous studies have suggested that SUMOylation of substrates plays critical roles in normal cardiovascular development and function. We reviewed the research progress of SUMOylation in cardiovascular development and function, and the regulation of protein SUMOylation may be applied as a potential therapeutic strategy for CVD treatment.

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Roles of SUMOylation in Heart Development and Cardiovascular Diseases

Cited by 12 publications

References 0 publications

Ginkgolic Acid Rescues Lens Epithelial Cells from Injury Caused by Redox Regulated-Aberrant Sumoylation Signaling by Reviving Prdx6 and Sp1 Expression and Activities

Ginkgolic Acid Rescues Lens Epithelial Cells from Injury Caused by Redox Regulated-Aberrant Sumoylation Signaling by Reviving Prdx6 and Sp1 Expression and Activities

OUP accepted manuscript

The Function of SUMOylation and Its Critical Roles in Cardiovascular Diseases and Potential Clinical Implications

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