Identification and Quantification of Glutathionylated Cysteines under Ischemic Stress.
Maheeshi Yapa AbeywardanaKusal T G SamarasingheDhanushka Munkanatta GodageYoung-Hoon AhnPublished in: Journal of proteome research (2021)
Ischemia reperfusion injury contributes to adverse cardiovascular diseases in part by producing a burst of reactive oxygen species that induce oxidations of many muscular proteins. Glutathionylation is one of the major protein cysteine oxidations that often serve as molecular mechanisms behind the pathophysiology associated with ischemic stress. Despite the biological significance of glutathionylation in ischemia reperfusion, identification of specific glutathionylated cysteines under ischemic stress has been limited. In this report, we have analyzed glutathionylation under oxygen-glucose deprivation (OGD) or repletion of nutrients after OGD (OGD/R) by using a clickable glutathione approach that specifically detects glutathionylated proteins. Our data find that palmitate availability induces a global level of glutathionylation and decreases cell viability during OGD/R. We have then applied a clickable glutathione-based proteomic quantification strategy, which enabled the identification and quantification of 249 glutathionylated cysteines in response to palmitate during OGD/R in the HL-1 cardiomyocyte cell line. The subsequent bioinformatic analysis found 18 glutathionylated cysteines whose genetic variants are associated with muscular disorders. Overall, our data report glutathionylated cysteines under ischemic stress that may contribute to adverse outcomes or muscular disorders.
Keyphrases
- ischemia reperfusion injury
- reactive oxygen species
- cardiovascular disease
- electronic health record
- oxidative stress
- stress induced
- resistance training
- cerebral ischemia
- bioinformatics analysis
- adipose tissue
- big data
- emergency department
- blood brain barrier
- high intensity
- high frequency
- type diabetes
- brain injury
- weight loss
- coronary artery disease
- artificial intelligence
- data analysis
- binding protein
- amino acid
- adverse drug