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Cardioprotective 3′,4′-dihydroxyflavonol attenuation of JNK and p38MAPK signalling involves CaMKII inhibition

Overview of attention for article published in Biochemical Journal, November 2013
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Cardioprotective 3′,4′-dihydroxyflavonol attenuation of JNK and p38MAPK signalling involves CaMKII inhibition
Published in
Biochemical Journal, November 2013
DOI 10.1042/bj20121538
Pubmed ID

Nicholas R. Lim, Colleen J. Thomas, Lokugan S. Silva, Yvonne Y. Yeap, Suwan Yap, James R. Bell, Lea M. D. Delbridge, Marie A. Bogoyevitch, Owen L. Woodman, Spencer J. Williams, Clive N. May, Dominic C. H. Ng


DiOHF (3',4'-dihydroxyflavonol) is cardioprotective against I/R (ischaemia/reperfusion) injury. The biological activities of flavonols are associated with kinase modulation to alter cell signalling. We thus investigated the effects of DiOHF on the activation of MAPKs (mitogen-activated protein kinases) that regulate the cardiac stress response. In an ovine model of I/R, JNK (c-Jun N-terminal kinase), p38(MAPK), ERK (extracellular-signal-regulated kinase) and Akt were activated, and NP202, a pro-drug of DiOHF, reduced infarct size and inhibited JNK and p38(MAPK) activation, whereas ERK and Akt phosphorylation were unaltered. Similarly, in cultured myoblasts, DiOHF pre-treatment preserved viability and inhibited activation of JNK and p38(MAPK), but not ERK in response to acute oxidative and chemotoxic stress. Furthermore, DiOHF prevented stress-activation of the direct upstream regulators MKK4/7 (MAPK kinase 4/7) and MKK3/6 respectively. We utilized small-molecule affinity purification and identified CaMKII (Ca(2+)/calmodulin-dependent protein kinase II) as a kinase targeted by DiOHF and demonstrated potent CaMKII inhibition by DiOHF in vitro. Moreover, the specific inhibition of CaMKII with KN-93, but not KN-92, prevented oxidative stress-induced activation of JNK and p38(MAPK). The present study indicates DiOHF inhibition of CaMKII and attenuation of MKK3/6→p38(MAPK) and MKK4/7→JNK signalling as a requirement for the protective effects of DiOHF against stress stimuli and myocardial I/R injury.

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Mendeley readers

The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 16 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 38%
Student > Master 2 13%
Professor 1 6%
Student > Bachelor 1 6%
Librarian 1 6%
Other 3 19%
Unknown 2 13%
Readers by discipline Count As %
Agricultural and Biological Sciences 5 31%
Medicine and Dentistry 4 25%
Nursing and Health Professions 1 6%
Business, Management and Accounting 1 6%
Biochemistry, Genetics and Molecular Biology 1 6%
Other 2 13%
Unknown 2 13%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 November 2013.
All research outputs
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Outputs of similar age
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Outputs of similar age from Biochemical Journal
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Altmetric has tracked 6,535,297 research outputs across all sources so far. This one has received more attention than most of these and is in the 52nd percentile.
So far Altmetric has tracked 4,207 research outputs from this source. They receive a mean Attention Score of 2.7. This one is in the 29th percentile – i.e., 29% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 101,228 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 9 others from the same source and published within six weeks on either side of this one. This one has scored higher than 3 of them.