Journal article
SMYD2 glutathionylation contributes to degradation of sarcomeric proteins
Nature communications, v 9(1), pp 4341-14
18 Oct 2018
PMID: 30337525
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Reactive oxygen species (ROS) contribute to the etiology of multiple muscle-related diseases. There is emerging evidence that cellular stress can lead to destabilization of sarcomeres, the contractile unit of muscle. However, it is incompletely understood how cellular stress induces structural destabilization of sarcomeres. Here we report that glutathionylation of SMYD2 contributes to a loss of myofibril integrity and degradation of sarcomeric proteins mediated by MMP-2 and calpain 1. We used a clickable glutathione approach in a cardiomyocyte cell line and found selective glutathionylation of SMYD2 at Cys13. Biochemical analysis demonstrated that SMYD2 upon oxidation or glutathionylation at Cys13 loses its interaction with Hsp90 and N2A, a domain of titin. Upon dissociation from SMYD2, N2A or titin is degraded by activated MMP-2, suggesting a protective role of SMYD2 in sarcomere stability. Taken together, our results support that SMYD2 glutathionylation is a novel molecular mechanism by which ROS contribute to sarcomere destabilization.
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Details
- Title
- SMYD2 glutathionylation contributes to degradation of sarcomeric proteins
- Creators
- Dhanushka N. P. Munkanatta Godage - Wayne State UniversityGarrett C. VanHecke - Wayne State UniversityKusal T. G. Samarasinghe - Wayne State UniversityHan-Zhong Feng - Wayne State UniversityMark Hiske - Wayne State UniversityJoshua Holcomb - Wayne State UniversityZhe Yang - Wayne State UniversityJian-Ping Jin - Wayne State UniversityCharles S. Chung - Wayne State UniversityYoung-Hoon Ahn - Wayne State University
- Publication Details
- Nature communications, v 9(1), pp 4341-14
- Publisher
- Springer Nature
- Number of pages
- 14
- Grant note
- R01 HL131740-01A1 / National Institute of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30 CA 02253 / NIH Cancer Center Support Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA S10OD010700 / OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30ES020957 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) Wayne State University Start-up fund P30 ES 020957; P30 CA022453 / NIH Center Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01HL131740 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) S10 OD 010700 / NIH Shared Instrumentation Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30CA022453 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Arts and Sciences; Chemistry; Drexel University
- Web of Science ID
- WOS:000447584400008
- Scopus ID
- 2-s2.0-85055079099
- Other Identifier
- 991020100059804721
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- Web of Science research areas
- Biochemistry & Molecular Biology