Evidence map›Paper›PMID 27362462›Full record

ArticleJournal of proteome research2016

Top-Down Targeted Proteomics Reveals Decrease in Myosin Regulatory Light-Chain Phosphorylation That Contributes to Sarcopenic Muscle Dysfunction.

Zachery R Gregorich, Ying Peng, Wenxuan Cai, Yutong Jin, Liming Wei, Albert J Chen, Susan H McKiernan, Judd M Aiken, Richard L Moss, Gary M Diffee and 1 more

Abstract read
In one paragraph

Article in Journal of proteome research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.5field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
  2. Review
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  9. Article
  10. Top-down proteomics.Nature reviews. Methods primers · 2024
    Article
  11. Review
  12. High sensitivity top-down proteomics captures single muscle cell heterogeneity in large proteoforms.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Novel Strategies to Address the Challenges in Top-Down Proteomics.Journal of the American Society for Mass Spectrometry · 2021
    Review
  18. CaAmerican journal of physiology. Cell physiology · 2020
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 3 countries.

Zachery R GregorichDepartment of Cell and Regenerative Biology, University of Wisconsin-Madison , 1111 Highland Avenue, Madison, Wisconsin 53705, United States.
Ying PengDepartment of Cell and Regenerative Biology, University of Wisconsin-Madison , 1111 Highland Avenue, Madison, Wisconsin 53705, United States.
Wenxuan CaiDepartment of Cell and Regenerative Biology, University of Wisconsin-Madison , 1111 Highland Avenue, Madison, Wisconsin 53705, United States.
Yutong JinDepartment of Cell and Regenerative Biology, University of Wisconsin-Madison , 1111 Highland Avenue, Madison, Wisconsin 53705, United States.
Liming WeiDepartment of Cell and Regenerative Biology, University of Wisconsin-Madison , 1111 Highland Avenue, Madison, Wisconsin 53705, United States.
Albert J ChenDepartment of Cell and Regenerative Biology, University of Wisconsin-Madison , 1111 Highland Avenue, Madison, Wisconsin 53705, United States.
Susan H McKiernanDepartment of Kinesiology, University of Wisconsin-Madison , 2000 Observatory Drive, Madison, Wisconsin 53705, United States.
Judd M AikenDepartments of Agriculture, Food, and Nutritional Sciences, University of Alberta-Edmonton , Edmonton, Alberta, Canada.
Richard L MossDepartment of Cell and Regenerative Biology, University of Wisconsin-Madison , 1111 Highland Avenue, Madison, Wisconsin 53705, United States.
Gary M DiffeeDepartment of Kinesiology, University of Wisconsin-Madison , 2000 Observatory Drive, Madison, Wisconsin 53705, United States.
Ying GeDepartment of Cell and Regenerative Biology, University of Wisconsin-Madison , 1111 Highland Avenue, Madison, Wisconsin 53705, United States.
University of Wisconsin–Madison · USFudan University · CNUniversity of Alberta · CA

Funding

Training Program In Molecular AND Cellular PharmacologyT32GM008688 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI AUDHYA, ANJON · 1998 to 2020
$6.0M
Deciphering Myofilament Modifications in Ischemic CardiomyopathyR01HL109810 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI GE, YING · 2013 to 2024
$3.5M
Top Down Proteomics Of Myofilaments In Heart FailureR01HL096971 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI GE, YING · 2011 to 2021
$3.3M
Enabling Top-Down Proteomics through Materials Chemistry and NanotechnologyR01GM117058 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI GE, YING, JIN, SONG · 2015 to 2023
$2.7M
Impact of Exercise on SarcopeniaR01AG030423 · NIA · UNIVERSITY OF ALBERTA · PI AIKEN, JUDD M. · 2009 to 2013
$2.1M
Ultra High Resolution Mass Spectrometer for Biomedical ResearchS10OD018475 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI GE, YING · 2015 to 2015
$2.0M
A systems biology approach to understanding the role of myofilaments in cardiac regenerationF31HL128086 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI GREGORICH, ZACHERY ROBERT · 2015 to 2016
$60k
NHLBI NIH HHS F31 HL128086NHLBI NIH HHS R01 HL096971NHLBI NIH HHS R01 HL109810NIA NIH HHS R01 AG030423NIGMS NIH HHS R01 GM117058NIGMS NIH HHS T32 GM008688NIH HHS S10 OD018475
6 · The paper itself

Abstract

Sarcopenia, the loss of skeletal muscle mass and function with advancing age, is a significant cause of disability and loss of independence in the elderly and thus, represents a formidable challenge for the aging population. Nevertheless, the molecular mechanism(s) underlying sarcopenia-associated muscle dysfunction remain poorly understood. In this study, we employed an integrated approach combining top-down targeted proteomics with mechanical measurements to dissect the molecular mechanism(s) in age-related muscle dysfunction. Top-down targeted proteomic analysis uncovered a progressive age-related decline in the phosphorylation of myosin regulatory light chain (RLC), a critical protein involved in the modulation of muscle contractility, in the skeletal muscle of aging rats. Top-down tandem mass spectrometry analysis identified a previously unreported bis-phosphorylated proteoform of fast skeletal RLC and localized the sites of decreasing phosphorylation to Ser14/15. Of these sites, Ser14 phosphorylation represents a previously unidentified site of phosphorylation in RLC from fast-twitch skeletal muscle. Subsequent mechanical analysis of single fast-twitch fibers isolated from the muscles of rats of different ages revealed that the observed decline in RLC phosphorylation can account for age-related decreases in the contractile properties of sarcopenic fast-twitch muscles. These results strongly support a role for decreasing RLC phosphorylation in sarcopenia-associated muscle dysfunction and suggest that therapeutic modulation of RLC phosphorylation may represent a new avenue for the treatment of sarcopenia.

Indexed as

AgingAnimalsMuscle ContractionMuscle Fibers, Fast-TwitchMuscle, SkeletalMyosin Light ChainsPhosphorylationProteomicsRatsSarcopeniaTandem Mass SpectrometryMyosin Light Chainsagingmyofilamentsarcopeniatargeted proteomicstop-down mass spectrometry

Identifiers

PMID27362462
PMCPMC4975644
OpenAlexW2466965833

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.