Inhibition of myeloid HDAC2 upregulates glutaredoxin 1 expression improves protein thiol redox state and protects against high calorie diet-induced monocyte dysfunction and atherosclerosis.

2021 ◽  
Vol 331 ◽  
pp. e31
Author(s):  
L. Wang ◽  
Y.J. Ahn ◽  
R. Asmis
2021 ◽  
Author(s):  
Ahmet Tuncay ◽  
Anna Noble ◽  
Matthew Guille ◽  
James Cobley

Abstract An accessible, time- and cost-efficient microplate assay to quantify protein thiol redox state in percentages and moles relative to the thiol proteome (i.e., context) and other targets (i.e., array mode) would be invaluable for understanding how protein thiols regulate essential biological processes. RedoxiFluor achieves several key benefits (i.e., percentages, moles, context, array mode) in a microplate format. After robustly validating RedoxiFluor, comparative analysis reveals that key benefits are intractable to other immunological techniques. Moles is an unprecedented achievement. Proof-of-concept studies illuminating fundamental redox principles (i.e., specificity, context, and heterogeneity) through measurement alone demonstrate how RedoxiFluor can advance understanding. For example, target specific protein thiol redox state changes are: (1) context specific (i.e., redox stimulus dependent); (2) selective (i.e., redox stimuli oxidise select targets); and (3) heterogenous (i.e., target responses vary markedly). RedoxiFluor is a powerful new tool for advancing a far-reaching and influential field: protein thiol redox biology.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ying Ann Chiao ◽  
Huiliang Zhang ◽  
Mariya Sweetwyne ◽  
Jeremy Whitson ◽  
Ying Sonia Ting ◽  
...  

Diastolic dysfunction is a prominent feature of cardiac aging in both mice and humans. We show here that 8-week treatment of old mice with the mitochondrial targeted peptide SS-31 (elamipretide) can substantially reverse this deficit. SS-31 normalized the increase in proton leak and reduced mitochondrial ROS in cardiomyocytes from old mice, accompanied by reduced protein oxidation and a shift towards a more reduced protein thiol redox state in old hearts. Improved diastolic function was concordant with increased phosphorylation of cMyBP-C Ser282 but was independent of titin isoform shift. Late-life viral expression of mitochondrial-targeted catalase (mCAT) produced similar functional benefits in old mice and SS-31 did not improve cardiac function of old mCAT mice, implicating normalizing mitochondrial oxidative stress as an overlapping mechanism. These results demonstrate that pre-existing cardiac aging phenotypes can be reversed by targeting mitochondrial dysfunction and implicate mitochondrial energetics and redox signaling as therapeutic targets for cardiac aging.


2021 ◽  
Vol 174 ◽  
pp. 272-280 ◽  
Author(s):  
Anna Noble ◽  
Matthew Guille ◽  
James N. Cobley

Author(s):  
Raquel Requejo ◽  
Edward T. Chouchani ◽  
Thomas R. Hurd ◽  
Katja E. Menger ◽  
Mark B. Hampton ◽  
...  

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 315 ◽  
Author(s):  
James Nathan Cobley ◽  
Holger Husi

To understand oxidative stress, antioxidant defense, and redox signaling in health and disease it is essential to assess protein thiol redox state. Protein thiol redox state is seldom assessed immunologically because of the inability to distinguish reduced and reversibly oxidized thiols by Western blotting. An underappreciated opportunity exists to use Click PEGylation to realize the transformative power of simple, time and cost-efficient immunological techniques. Click PEGylation harnesses selective, bio-orthogonal Click chemistry to separate reduced and reversibly oxidized thiols by selectively ligating a low molecular weight polyethylene glycol moiety to the redox state of interest. The resultant ability to disambiguate reduced and reversibly oxidized species by Western blotting enables Click PEGylation to assess protein thiol redox state. In the present review, to enable investigators to effectively harness immunological techniques to assess protein thiol redox state we critique the chemistry, promise and challenges of Click PEGylation.


Author(s):  
Ying Ann Chiao ◽  
Huiliang Zhang ◽  
Mariya Sweetwyne ◽  
Jeremy Whitson ◽  
Ying Sonia Ting ◽  
...  

AbstractDiastolic dysfunction is a prominent feature of cardiac aging in both mice and humans. We show here that 8-week treatment of old mice with the mitochondrial targeted peptide SS-31 (elamipretide) can substantially reverse this deficit. SS-31 normalized the increase in proton leak and reduced mitochondrial ROS in cardiomyocytes from old mice, accompanied by reduced protein oxidation and a shift towards a more reduced protein thiol redox state in old hearts. Improved diastolic function was concordant with increased phosphorylation of cMyBP-C Ser282 but was independent of titin isoform shift. Late-life viral expression of mitochondrial-targeted catalase (mCAT) produced similar functional benefits in old mice and SS-31 did not improve cardiac function of old mCAT mice, implicating normalizing mitochondrial oxidative stress as an overlapping mechanism. These results demonstrate that pre-existing cardiac aging phenotypes can be reversed by targeting mitochondrial dysfunction and implicate mitochondrial energetics and redox signaling as therapeutic targets for cardiac aging.


2020 ◽  
Vol 33 (1) ◽  
pp. 38-44
Author(s):  
Alona Yurchenko ◽  
Daryna Krenytska ◽  
Olexii Savchuk ◽  
Tetiana Halenova ◽  
Natalia Raksha ◽  
...  

AbstractOur interest has focused on the investigation of the anti-obese potential of kidney beans (P. vulgaris) pods extract. In the course of the study, obesity development in rats was induced with high-calorie diet. Control and obese rats then have consumed with aqueous kidney beans (P. vulgaris) pods extract during 6 weeks (200 mg/kg). Results show that the long-term consumption of P. vulgaris pods extract can lead to the reduction of hyperglycemia and insulin resistance development. Furthermore, we saw a normalization of lipid peroxidation parameters and oxidative modification of protein due to the consumption of the kidney beans (P. vulgaris) pods extract. Our experimental data demonstrate the ability of the kidney beans (P. vulgaris) pod extracts to mitigate obesity development but the details of this mechanism remains to be not fully understood.


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