Dataset Information

Substance P enhances the local activation of NK₁R-expressing c-kit⁺ cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart.

ABSTRACT:

Background

Localization of neurokinin 1 receptor (NK₁R), the endogenous receptor for neuropeptide substance P (SP), has already been described for the right atrium (RA) of the heart. However, the biological role of SP/NK₁R signal pathways in the RA remains unclear. Sprague-Dawley rats were randomly divided into 4 groups (n?=?22 each); subjected to sham, ischemia/reperfusion-injury (I/R), I/R with 5 nmole/kg SP injection (SP?+?I/R), and SP?+?I/R with 1?mg/kg RP67580 injection (RP, a selective non-peptide tachykinin NK₁R antagonist) (RP/SP?+?I/R). The left anterior descending coronary artery was occluded for 40?min followed by 1?day reperfusion with SP or SP?+?RP or without either. After 1?day, both atria and ventricles as well as the heart apexes were collected.

Results

SP promoted the expression of c-Kit, GATA4, Oct4, Nanog, and Sox2 in only the RA of the SP?+?I/R rats via NK₁R activation. In agreement with these observations, NK₁R-expressing c-Kit⁺ Nkx2.5⁺GATA4⁺ cardiac progenitor cells (CPCs) in the ex vivo RA explant outgrowth assay markedly migrated out from RA^{1 day SP?+?I/R} approximately 2-fold increase more than RA^{1 day I/R}. Treatment of SP promoted proliferation, migration, cardiosphere formation, and potential to differentiate into cardiomyocytes. Using RP inhibitor, NK₁R antagonist not only inhibited cell proliferation and migration but also reduced the formation of cardiosphere and differentiation of c-Kit⁺ CPCs.

Conclusion

SP/NK₁R might play a role as a key mediator involved in the cellular response to c-Kit⁺ CPC expansion in RA of the heart within 24?h after I/R.

SUBMITTER: Jeong YM

PROVIDER: S-EPMC7285458 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Substance P enhances the local activation of NK<sub>1</sub>R-expressing c-kit<sup>+</sup> cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart.

Jeong Yun-Mi YM Cheng Xian Wu XW Lee Kyung Hye KH Lee Sora S Cho Haneul H Kim Weon W

BMC molecular and cell biology 20200609 1

<h4>Background</h4>Localization of neurokinin 1 receptor (NK<sub>1</sub>R), the endogenous receptor for neuropeptide substance P (SP), has already been described for the right atrium (RA) of the heart. However, the biological role of SP/NK<sub>1</sub>R signal pathways in the RA remains unclear. Sprague-Dawley rats were randomly divided into 4 groups (n = 22 each); subjected to sham, ischemia/reperfusion-injury (I/R), I/R with 5 nmole/kg SP injection (SP + I/R), and SP + I/R with 1 mg/kg RP67580 ...[more]

PMID: 32517655

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Project description:Introduction:The effects of exercise on the heart and its resistance to disease are well-documented. Recent studies have identified that exercise-induced resistance to arrhythmia is due to the preservation of mitochondrial membrane potential. Objectives:To identify novel metabolic changes that occur parallel to these mitochondrial alterations, we performed non-targeted metabolomics analysis on hearts from sedentary and exercise-trained rats challenged with isolated heart ischemia-reperfusion injury (I/R). Methods:Eight-week old Sprague-Dawley rats were treadmill trained 5 days/week for 6 weeks (exercise duration and intensity progressively increased to 1 h at 30 m/min up a 10.5% incline, 75-80% VO2max). The recovery of pre-ischemic function for sedentary rat hearts was 28.8 ± 5.4% (N = 12) compared to exercise trained hearts, which recovered 51.9% ± 5.7 (N = 14) (p < 0.001). Results:Non-targeted GC-MS metabolomics analysis of (1) sedentary rat hearts; (2) exercise-trained rat hearts; (3) sedentary rat hearts challenged with global ischemia-reperfusion (I/R) injury; and (4) exercise-trained rat hearts challenged with global I/R (10/group) revealed 15 statistically significant metabolites between groups by ANOVA using Metaboanalyst (p < 0.001). Enrichment analysis of these metabolites for pathway-associated metabolic sets indicated a > 10-fold enrichment for ammonia recycling and protein biosynthesis. Subsequent comparison of the sedentary hearts post-I/R and exercise-trained hearts post-I/R further identified significant differences in three metabolites (oleic acid, pantothenic acid, and campesterol) related to pantothenate and CoA biosynthesis (p ? 1.24E-05, FDR ? 5.07E-4). Conclusions:These studies shed light on novel mechanisms in which exercise-induced cardioprotection occurs in I/R that complement both the mitochondrial stabilization and antioxidant mechanisms recently described. These findings also link protein synthesis and protein degradation (protein quality control mechanisms) with exercise-linked cardioprotection and mitochondrial susceptibility for the first time in cardiac I/R.

Project description:Aim: Hepatic ischemia-reperfusion (HIR) induces remote organs injury, including the brain. The homeostasis of the brain is maintained by the blood-brain barrier (BBB); thus, we aimed to investigate whether HIR impaired BBB and attempted to elucidate its underlying mechanism. Methods: Cell viability of human cerebral microvascular endothelial cells (hCMEC/D3) was measured following 24 h incubation with a serum of HIR rat undergoing 1 h ischemia and 4 h reperfusion, liver homogenate, or lysate of primary hepatocytes of the rat. The liver homogenate was precipitated using (NH4)2SO4 followed by separation on three columns and electrophoresis to identify the toxic molecule. Cell activity, apoptosis, proliferation, cell cycle, and expressions of proteins related to cell cycle were measured in hCMEC/D3 cells incubated with identified toxic molecules. HIR rats undergoing 1 h ischemia and 24 h reperfusion were developed to determine the release of an identified toxic molecule. BBB function was indexed as permeability to fluorescein and brain water. Endothelial cell proliferation and expressions of proteins related to the cell cycle in cerebral microvessels were measured by immunofluorescence and western blot. Results: Toxic molecule to BBB in the liver was identified to be arginase. Arginase inhibitor nor-NOHA efficiently attenuated hCMEC/D3 damage caused by liver homogenate and serum of HIR rats. Both arginase and serum of HIR rats significantly lowered arginine (Arg) in the culture medium. Arg addition efficiently attenuated the impairment of hCMEC/D3 caused by arginase or Arg deficiency, demonstrating that arginase impaired hCMEC/D3 via depriving Arg. Both arginase and Arg deficiency damaged hCMEC/D3 cells by inhibiting cell proliferation, retarding the cell cycle to G1 phase, and downregulating expressions of cyclin A, cyclin D, CDK2, and CDK4. HIR notably increased plasma arginase activity and lowered Arg level, increased the BBB permeability accompanied with enhanced brain water, and decreased the proliferative cells (marked by Ki67) in cerebral microvessels (marked by CD31) and protein expressions of cyclin A, cyclin D, CDK2 and CDK4 in isolated brain microvessels. Oral supplement of Arg remarkably attenuated these HIR-induced alterations. Conclusion: HIR leads to substantial release of arginase from the injured liver and then deprives systemic Arg. The Arg deficiency further impairs BBB via inhibiting the proliferation of brain microvascular endothelial cells by cell cycle arrest.

Dataset Information

Substance P enhances the local activation of NK₁R-expressing c-kit⁺ cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart.

Background

Results

Conclusion

Publications

Substance P enhances the local activation of NK<sub>1</sub>R-expressing c-kit<sup>+</sup> cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart.

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OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Substance P enhances the local activation of NK1R-expressing c-kit+ cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart.

Background

Results

Conclusion

Publications

Substance P enhances the local activation of NK<sub>1</sub>R-expressing c-kit<sup>+</sup> cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Substance P enhances the local activation of NK₁R-expressing c-kit⁺ cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart.