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Brain-derived neurotrophic factor regulates TRPC3/6 channels and protects against myocardial infarction in rodents.

Hang P, Zhao J, Cai B, Tian S, Huang W, Guo J, Sun C, Li Y, Du Z - Int. J. Biol. Sci. (2015)

Bottom Line: Meanwhile, echocardiography indicated that BDNF significantly improved cardiac function of MI mice.Furthermore, protective role of BDNF against hypoxia-induced apoptosis was reversed by 2-APB and TRPC3/6 siRNAs.BDNF/TrkB alleviated cardiac ischemic injury and inhibited cardiomyocytes apoptosis by regulating TRPC3/6 channels, which provides a novel potential therapeutic candidate for MI.

View Article: PubMed Central - PubMed

Affiliation: 1. Institute of Clinical Pharmacology of the Second Affiliated Hospital (Key Laboratory of Drug Research, Heilongjiang Higher Education Institutions), Harbin Medical University, Harbin 150086, China.

ABSTRACT

Background: Brain-derived neurotrophic factor (BDNF) is associated with coronary artery diseases. However, its role and mechanism in myocardial infarction (MI) is not fully understood.

Methods: Wistar rat and Kunming mouse model of MI were induced by the ligation of left coronary artery. Blood samples were collected from MI rats and patients. Plasma BDNF level, protein expression of BDNF, tropomyosin-related kinase B (TrkB) and its downstream transient receptor potential canonical (TRPC)3/6 channels were examined by enzyme-linked immunosorbent assay and Western blot. Infarct size, cardiac function and cardiomyocyte apoptosis were measured after intra-myocardium injection with recombinant human BDNF. Protective role of BDNF against cardiomyocyte apoptosis was confirmed by BDNF scavenger TrkB-Fc. The regulation of TRPC3/6 channels by BDNF was validated by pretreating with TRPC blocker (2-Aminoethyl diphenylborinate, 2-APB) and TRPC3/6 siRNAs.

Results: Circulating BDNF was significantly enhanced in MI rats and patients. Protein expression of BDNF, TrkB and TRPC3/6 channels were upregulated in MI. 3 days post-MI, BDNF treatment markedly reduced the infarct size and serum lactate dehydrogenase activity. Meanwhile, echocardiography indicated that BDNF significantly improved cardiac function of MI mice. Furthermore, BDNF markedly inhibited cardiomyocyte apoptosis by upregulating Bcl-2 expression and downregulating caspase-3 expression and activity in ischemic myocardium. In neonatal rat ventricular myocytes, cell viability was dramatically increased by BDNF in hypoxia, which was restored by TrkB-Fc. Furthermore, protective role of BDNF against hypoxia-induced apoptosis was reversed by 2-APB and TRPC3/6 siRNAs.

Conclusion: BDNF/TrkB alleviated cardiac ischemic injury and inhibited cardiomyocytes apoptosis by regulating TRPC3/6 channels, which provides a novel potential therapeutic candidate for MI.

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Plasma BDNF concentration in myocardial infarction (MI) rats and human. (A) Plasma BDNF levels were measured in sham and ischemia for 1 h, 6 h and 24 h by ELISA. (B) Plasma BDNF concentration was measured in control and MI patients. *p <0.05 vs. sham, n = 4 each group, ***p<0.001 vs. control, n = 5 in control group while n = 7 in MI group.
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Figure 2: Plasma BDNF concentration in myocardial infarction (MI) rats and human. (A) Plasma BDNF levels were measured in sham and ischemia for 1 h, 6 h and 24 h by ELISA. (B) Plasma BDNF concentration was measured in control and MI patients. *p <0.05 vs. sham, n = 4 each group, ***p<0.001 vs. control, n = 5 in control group while n = 7 in MI group.

Mentions: First of all, we examined the plasma BDNF level in MI rats and human. ELISA assay showed that plasma BDNF level did not change at 1 h post-MI but significantly increased after MI for 6 h, and returned toward 1 h values by 24 h (Fig. 2A). Meanwhile, we observed that plasma BDNF level in MI patients was markedly enhanced compared with non-MI patients (Fig. 2B). Thus, these results suggested that circulating BDNF level was elevated in acute MI.


Brain-derived neurotrophic factor regulates TRPC3/6 channels and protects against myocardial infarction in rodents.

Hang P, Zhao J, Cai B, Tian S, Huang W, Guo J, Sun C, Li Y, Du Z - Int. J. Biol. Sci. (2015)

Plasma BDNF concentration in myocardial infarction (MI) rats and human. (A) Plasma BDNF levels were measured in sham and ischemia for 1 h, 6 h and 24 h by ELISA. (B) Plasma BDNF concentration was measured in control and MI patients. *p <0.05 vs. sham, n = 4 each group, ***p<0.001 vs. control, n = 5 in control group while n = 7 in MI group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4400385&req=5

Figure 2: Plasma BDNF concentration in myocardial infarction (MI) rats and human. (A) Plasma BDNF levels were measured in sham and ischemia for 1 h, 6 h and 24 h by ELISA. (B) Plasma BDNF concentration was measured in control and MI patients. *p <0.05 vs. sham, n = 4 each group, ***p<0.001 vs. control, n = 5 in control group while n = 7 in MI group.
Mentions: First of all, we examined the plasma BDNF level in MI rats and human. ELISA assay showed that plasma BDNF level did not change at 1 h post-MI but significantly increased after MI for 6 h, and returned toward 1 h values by 24 h (Fig. 2A). Meanwhile, we observed that plasma BDNF level in MI patients was markedly enhanced compared with non-MI patients (Fig. 2B). Thus, these results suggested that circulating BDNF level was elevated in acute MI.

Bottom Line: Meanwhile, echocardiography indicated that BDNF significantly improved cardiac function of MI mice.Furthermore, protective role of BDNF against hypoxia-induced apoptosis was reversed by 2-APB and TRPC3/6 siRNAs.BDNF/TrkB alleviated cardiac ischemic injury and inhibited cardiomyocytes apoptosis by regulating TRPC3/6 channels, which provides a novel potential therapeutic candidate for MI.

View Article: PubMed Central - PubMed

Affiliation: 1. Institute of Clinical Pharmacology of the Second Affiliated Hospital (Key Laboratory of Drug Research, Heilongjiang Higher Education Institutions), Harbin Medical University, Harbin 150086, China.

ABSTRACT

Background: Brain-derived neurotrophic factor (BDNF) is associated with coronary artery diseases. However, its role and mechanism in myocardial infarction (MI) is not fully understood.

Methods: Wistar rat and Kunming mouse model of MI were induced by the ligation of left coronary artery. Blood samples were collected from MI rats and patients. Plasma BDNF level, protein expression of BDNF, tropomyosin-related kinase B (TrkB) and its downstream transient receptor potential canonical (TRPC)3/6 channels were examined by enzyme-linked immunosorbent assay and Western blot. Infarct size, cardiac function and cardiomyocyte apoptosis were measured after intra-myocardium injection with recombinant human BDNF. Protective role of BDNF against cardiomyocyte apoptosis was confirmed by BDNF scavenger TrkB-Fc. The regulation of TRPC3/6 channels by BDNF was validated by pretreating with TRPC blocker (2-Aminoethyl diphenylborinate, 2-APB) and TRPC3/6 siRNAs.

Results: Circulating BDNF was significantly enhanced in MI rats and patients. Protein expression of BDNF, TrkB and TRPC3/6 channels were upregulated in MI. 3 days post-MI, BDNF treatment markedly reduced the infarct size and serum lactate dehydrogenase activity. Meanwhile, echocardiography indicated that BDNF significantly improved cardiac function of MI mice. Furthermore, BDNF markedly inhibited cardiomyocyte apoptosis by upregulating Bcl-2 expression and downregulating caspase-3 expression and activity in ischemic myocardium. In neonatal rat ventricular myocytes, cell viability was dramatically increased by BDNF in hypoxia, which was restored by TrkB-Fc. Furthermore, protective role of BDNF against hypoxia-induced apoptosis was reversed by 2-APB and TRPC3/6 siRNAs.

Conclusion: BDNF/TrkB alleviated cardiac ischemic injury and inhibited cardiomyocytes apoptosis by regulating TRPC3/6 channels, which provides a novel potential therapeutic candidate for MI.

Show MeSH
Related in: MedlinePlus