Differential hypertrophic effects of cardiotrophin-1 on adult cardiomyocytes from normotensive and spontaneously hypertensive rats

López, Natalia; Dı́ez, Javier; Fortuño, María Antonia

doi:10.1016/j.yjmcc.2006.03.433

Cited by 45 publications

(43 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A previous study demonstrated that LIFR plays a critical role in the cardiotrophin-1-induced longitudinal prolongation of cardiomyocytes during heart development (17). We verified the upregulation of LIFR, and the Western blot in Fig.…”

Section: Rod-shaped Morphology and Striation Pattern Were Preserved Isupporting

confidence: 79%

“…The increased expression of LIFR in 2-mo-old cTnI-K118C mouse ventricular muscle linked the cTnI-K118C mutation to a cell signaling pathway that has been demonstrated to have an essential role in longitudinal prolongation of rat cardiomyocytes via the function of the cardiotrophin-1 signaling pathway (17,29). The signals may originate from the altered contractility or through changes in Ca 2ϩ homeostasis due to altered troponin function.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A dominantly negative mutation in cardiac troponin I at the interface with troponin T causes early remodeling in ventricular cardiomyocytes

Wei

Jin

2014

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Wei H, Jin JP. A dominantly negative mutation in cardiac troponin I at the interface with troponin T causes early remodeling in ventricular cardiomyocytes. Am J Physiol Cell Physiol 307: C338-C348, 2014. First published June 4, 2014; doi:10.1152/ajpcell.00053.2014.-We previously reported a point mutation substituting Cys for Arg 111 in the highly conserved troponin T (TnT)-contacting helix of cardiac troponin I (cTnI) in wild turkey hearts (Biesiadecki et al. J Biol Chem 279: 13825-13832, 2004). This dominantly negative TnI-TnT interface mutation decreases the binding affinity of cTnI for TnT, impairs diastolic function, and blunts the ␤-adrenergic response of cardiac muscle (Wei et al. J Biol Chem 285: 27806 -27816, 2010). Here we further investigate cellular phenotypes of transgenic mouse cardiomyocytes expressing the equivalent mutation cTnI-K118C. Functional studies were performed on single adult cardiomyocytes after recovery in short-term culture from isolation stress. The amplitude of contraction and the velocities of shortening and relengthening were lower in cTnI-K118C cardiomyocytes than wild-type controls. The intracellular Ca 2ϩ transient was slower in cTnI-K118C cardiomyocytes than wild-type cells. cTnI-K118C cardiomyocytes also showed a weaker ␤-adrenergic response. The resting length of cTnI-K118C cardiomyocytes was significantly greater than that of age-matched wild-type cells, with no difference in cell width. The resting sarcomere was not longer, but slightly shorter, in cTnI-K118C cardiomyocytes than wild-type cells, indicating longitudinal addition of sarcomeres. More tri-and quadrinuclei cardiomyocytes were found in TnI-K118C than wild-type hearts, suggesting increased nuclear divisions. Whole-genome mRNA array and Western blots detected an increased expression of leukemia inhibitory factor receptor-␤ in the hearts of 2-mo-old cTnI-K118C mice, suggesting a signaling pathway responsible for the potent effect of cTnI-K118C mutation on early remodeling in cardiomyocytes.cardiac troponin I; culture of adult cardiomyocyte; prolongation of cardiomyocytes; myocardial remodeling TROPONIN I (TnI), the inhibitory subunit of the troponin complex, plays an essential role in the Ca 2ϩ regulation of striated muscle contraction (8,21,22). We previously reported a point mutation in cardiac TnI (cTnI) in wild turkeys that generates a single-amino acid substitution of Cys for Arg 111 (4). This residue is located in the ␣-helix interfacing with troponin T (TnT) in the I-T arm of the troponin complex (23, 26) and is highly conserved as Arg or Lys in the three muscle fiber type-specific (cardiac and slow and fast skeletal muscle) TnI isoforms in all vertebrate species examined (4, 12). Because of the variable length of the NH 2 -terminal segment, the residues in human and mouse cTnI corresponding to Arg 111 in turkey cTnI are Lys 117 and Lys 118 , respectively (12). Our previous studies demonstrated that the Arg 111 Cys substitution decreased binding affinity of turkey cTnI for cardiac TnT (4). Transgenic mouse...

show abstract

Section: Rod-shaped Morphology and Striation Pattern Were Preserved Isupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

A dominantly negative mutation in cardiac troponin I at the interface with troponin T causes early remodeling in ventricular cardiomyocytes

Wei

Jin

2014

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

“…Despite years of intensive research, the exact mechanisms mediating CT-1-induced cardiomyocyte hypertrophy are still not entirely clarified. Originally, activation of the JAK/STAT3 axis has been assigned the key role in the generation of a cardiac hypertrophic phenotype in response to CT-1 stimulation [88,116,127,140]. While it appears quite certain that CT-1-induced cardiac hypertrophy is independent of PI3-K/Akt signaling [140], recent findings indicate that the major pathway responsible for the hypertrophic responses to CT-1 is probably not the JAK/STAT3 pathway or the MEK1-ERK1/2 pathway, but signal transduction via the MEK5-ERK5 pathway [134].…”

Section: Cardiotrophin-1 and Its Potential Role In The Heartmentioning

confidence: 99%

Survival pathways in hypertrophy and heart failure: The gp130-STAT3 axis

2007

View full text Add to dashboard Cite

■ Abstract Circulating levels of interleukin (IL)-6 and related cytokines are elevated in patients with congestive heart failure and after myocardial infarction. Serum IL-6 concentrations are related to decreasing functional status of these patients and provide important prognostic information. Moreover, in the failing human heart, multiple components of the IL-6-glycoprotein (gp)130 receptor system are impaired, implicating an important role of this system in cardiac pathophysiology.Experimental studies have shown that the common receptor subunit of IL-6 cytokines is phosphorylated in response to pressure overload and myocardial infarction and that it subsequently activates at least three different downstream signaling pathways, the signal transducers and activators of transcription 1 and 3 (STAT1/3), the Src-homology tyrosine phosphatase 2 (SHP2)-Ras-ERK, and the PI3K-Akt system. Gp130 receptor mediated signaling promotes cardiomyocyte survival, induces hypertrophy, modulates cardiac extracellular matrix and cardiac function. In this regard, the gp130 receptor system and its main downstream mediator STAT3 play a key role in cardioprotection.This review summarizes the current knowledge of IL-6 cytokines, gp130 receptor and STAT3 signaling in the heart exposed to physiological (aging, pregnancy) and pathophysiological stress (ischemia, pressure overload, inflammation and cardiotoxic agents) with a special focus on the potential role of individual IL-6 cytokines.

show abstract

“…A large number of experimental studies demonstrate that CT-1 may induce myocardial hypertrophy 1,7 . It also has been shown that the expression of CT-1 in the post-MI heart issignificantly elevated 8 .…”

Section: Disscusionmentioning

confidence: 99%

CT-1 induces angiogenesis by regulating the ADMA/DDAH Pathway

Zheng¹,

Xiao²,

Jin³

et al. 2015

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

View full text Add to dashboard Cite

Background. Cardiotrophin-1 (CT-1), a member of the IL-6 superfamily, is elevated in the serum of patients with ischemic and valvular heart disease. In this study, we hypothesized that CT-1 induces endothelial cell angiogenesis and that the ADMA/DDAH pathway plays an important role in the process. Methods. pEGFP-N1-CTF1-GFP and pEGFP-N1 were constructed and used to transiently transfect to HUVECs, mediated by LipofectamineTM 2000. After transfection, the expression of CT-1 was examined by qRT-PCR and western blotting. Endothelial cell proliferation assay was evaluated using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) method. Migration assay was performed using transwell, tube formation test was examined on Matrigel, eNOSmRNA expression was assayed by qRT-PCR, DDAH I, DDAHII and VEGF expression were detected by western blotting, the level of ADMA and the activity of DDAH were measured by High Performance Liquid Chromatography, NOS activity and the concentration of NO were assayed by L-[3H] citrulline production from L-[3H]arginine. Results. Overexpression of CT-1, increased endothelial cell proliferation, migration and formation of blood vessels, upregulated the expression of eNOSmRNA, DDAHI, DDAHII and VEGF, elevated the activity of DDAH and NOS, decreased the level of ADMA and promoted NO synthesis. In contrast, ADMA partially inhibited the effects of CT-1 induction. Conclusions. Overexpression of CT-1 increases cell proliferation, migration and formation of blood vessels. This result also suggests that CT-1 may regulate angiogenesis through the ADMA/DDAH pathway.

show abstract

Differential hypertrophic effects of cardiotrophin-1 on adult cardiomyocytes from normotensive and spontaneously hypertensive rats

Cited by 45 publications

References 42 publications

A dominantly negative mutation in cardiac troponin I at the interface with troponin T causes early remodeling in ventricular cardiomyocytes

A dominantly negative mutation in cardiac troponin I at the interface with troponin T causes early remodeling in ventricular cardiomyocytes

Survival pathways in hypertrophy and heart failure: The gp130-STAT3 axis

CT-1 induces angiogenesis by regulating the ADMA/DDAH Pathway

Contact Info

Product

Resources

About