INT287853

Context Info Confidence 0.63 First Reported 2007 Last Reported 2007 Negated 0 Speculated 0 Reported most in Body Documents 1 Total Number 31 Disease Relevance 0.87 Pain Relevance 0.56

cytoplasm (Tnni3)

Anatomy Link Frequency hearts 4 myocytes 3 cardiomyocytes 3 filament 1 Tnni3 (Rattus norvegicus)

Pain Link Frequency Relevance Heat Thoracotomy 31 98.96 ketamine 31 93.36 adenocard 31 89.36 agonist 31 80.04 addiction 93 71.44 lidocaine 155 61.84 imagery 31 5.00

Disease Link Frequency Relevance Heat Targeted Disruption 93 94.72 Coronary Heart Disease 31 82.92 Myocardial Infarction 31 81.48 Hypertrophic Cardiomyopathy 31 21.24

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Additional evidence to support this notion originates from the observations that the final phosphorylation levels of cMyBP-C and cTnI in the cardiomyocyte suspension after PKA-treatment exceeded the average values in the Quiescence and Contraction group.

Phosphorylation (phosphorylation) of cTnI in cardiomyocyte

1) Confidence 0.63 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0.15 Pain Relevance 0

The ProQ Diamond stained 1D-gels are convenient to determine the overall degree of phosphorylation of high molecular weight proteins such as cMyBP-C, and very basic proteins such as cTnI.

Phosphorylation (phosphorylation) of cTnI

2) Confidence 0.63 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0 Pain Relevance 0

As expected from the absence of any difference in Fmax, Fpas, and ktr between groups, no significant correlations were observed between these parameters and the endogenous levels of cMyBP-C, cTnI and MLC-2 phosphorylation in tissue from the different animals.

Phosphorylation (phosphorylation) of cTnI

3) Confidence 0.63 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0 Pain Relevance 0

The correspondence between the cMyBP-C and cTnI phosphorylation levels in the Quiescence hearts perfused with 0.2 mM and 1.36 mM CaCl2 was unexpected.

Phosphorylation (phosphorylation) of cTnI in hearts

4) Confidence 0.63 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0 Pain Relevance 0.04

Therefore our results indicate the presence of a strong interaction between the effects of phosphorylation of cTnI and MLC-2 on Ca2+-sensitivity.

Phosphorylation (phosphorylation) of cTnI

5) Confidence 0.63 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0.07 Pain Relevance 0

Cardiac MyBP-C and cTnI phosphorylation were markedly increased (3.7-fold) in the Isoprenaline group relative to the Quiescence group (P<0.01).

Phosphorylation (phosphorylation) of cTnI

6) Confidence 0.63 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0 Pain Relevance 0

Significant differences were found in the phosphorylation of cMyBP-C, cTnI, MLC-1 and MLC-2 in the three groups (ANOVA),while cTnT phosphorylation (approximately 80% of total cTnT) remained the same.

Phosphorylation (phosphorylation) of cTnI

7) Confidence 0.63 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0 Pain Relevance 0

Fig. 6A, B Quantitative analysis of cMyBP-C and cTnI phosphorylation from 1D-gels by Pro-Q Diamond and Sypro Ruby staining.

Phosphorylation (phosphorylation) of cTnI

8) Confidence 0.63 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0 Pain Relevance 0

In quiescent Langendorff-perfused hearts MLC-1, MLC-2, cMyBP-C and cTnI were mainly dephosphorylated, indicating that the relevant balance had been shifted in favour of phosphatase activity.

Phosphorylation (dephosphorylated) of cTnI in hearts

9) Confidence 0.63 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0 Pain Relevance 0.07

The impact of saturating PKA-sensitive phosphorylation of cMyBP-C, cTnI and (possibly) titin on force development was studied by repeating the Ca2+-sensitivity measurements after incubation of the cardiomyocytes with the active subunit of PKA.

Phosphorylation (phosphorylation) of cTnI in cardiomyocytes

10) Confidence 0.63 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0 Pain Relevance 0.04

The cMyBP-C and cTnI phosphorylation levels in the Quiescence and Contraction group were very similar.

Phosphorylation (phosphorylation) of cTnI

11) Confidence 0.63 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0.08 Pain Relevance 0

An overview of differences in phosphorylation of cMyBP-C, cTnI and MLC-2 in the Quiescence, Contraction and Isoprenaline group is shown in Fig. 6A, B and C, respectively.

Phosphorylation (phosphorylation) of cTnI

12) Confidence 0.63 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0 Pain Relevance 0

The increases in cMyBP-C and cTnI phosphorylation are consistent with literature data (e. g. [5]) and can be attributed to the increased activity of PKA but, because of the associated rise in the time-averaged intracellular Ca2+ concentration [2], altered activities of the Ca2+-dependent kinases CaMK II and classical PKC isoforms and, indirectly, of phosphatases such as PP-1 [22] may be involved as well.

Phosphorylation (phosphorylation) of cTnI

13) Confidence 0.63 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0 Pain Relevance 0

Since cMyBP-C and cTnI phosphorylation are strongly associated (Fig. 6D), it is not possible from these experiments to distinguish directly between effects of cMyBP-C and cTnI phosphorylation on Ca2+-sensitivity of force development.

Phosphorylation (phosphorylation) of cTnI

14) Confidence 0.63 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0.09 Pain Relevance 0

Since cMyBP-C and cTnI phosphorylation are strongly associated (Fig. 6D), it is not possible from these experiments to distinguish directly between effects of cMyBP-C and cTnI phosphorylation on Ca2+-sensitivity of force development.

Phosphorylation (phosphorylation) of cTnI

15) Confidence 0.63 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0.08 Pain Relevance 0

The averaged levels of cMyBP-C and cTnI phosphorylation in the Contraction group were not significantly increased.

Phosphorylation (phosphorylation) of cTnI

16) Confidence 0.63 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0 Pain Relevance 0.07

The endogenous phosphorylation levels of contractile proteins in TCA-treated tissue from the flash frozen hearts were determined from 2D-gels (cTnT, MLC-1 and MLC-2) and from ProQ Diamond stained 1D-gels (cMyBP-C, cTnT, cTnI and MLC-2).

Phosphorylation (phosphorylation) of cTnI in hearts

17) Confidence 0.63 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0 Pain Relevance 0

The notion that Isoprenaline phosphorylates other sites on cTnI and cMyBP-C is supported by the observation that the phosphorylation levels attained exceeded those obtained in the myocyte suspension after PKA treatment.

Phosphorylation (phosphorylates) of cTnI in myocyte

18) Confidence 0.63 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0 Pain Relevance 0

These experiments indicate that the PKA-sensitive phosphorylation sites on cMyBP-C and/or cTnI were not saturated under basal conditions even in the Isoprenaline group.

Phosphorylation (phosphorylation) of cTnI

19) Confidence 0.55 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0.16 Pain Relevance 0

Addition of Isoprenaline to the electrically paced (5 Hz) heart caused marked elevations of the cMyBP-C and cTnI phosphorylation levels, but did not result in a further significant increase in MLC-2 phosphorylation.

Phosphorylation (phosphorylation) of cTnI in heart

20) Confidence 0.49 Published 2007 Journal Basic Res Cardiol Section Body Doc Link PMC2780643 Disease Relevance 0 Pain Relevance 0.03

General Comments

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