Limits...
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.

Show MeSH

Related in: MedlinePlus

Effect of BDNF on cardiomyocytes apoptosis in mice 3 days post-MI. (A, B) The mRNA level of Bcl-2 and caspase-3. (C) Representative bands of protein expression of Bcl-2. (D) Caspase-3 activity. *p<0.05 vs. sham, #p<0.05 vs. MI, n = 4 mice each group.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4400385&req=5

Figure 6: Effect of BDNF on cardiomyocytes apoptosis in mice 3 days post-MI. (A, B) The mRNA level of Bcl-2 and caspase-3. (C) Representative bands of protein expression of Bcl-2. (D) Caspase-3 activity. *p<0.05 vs. sham, #p<0.05 vs. MI, n = 4 mice each group.

Mentions: We further examined the apoptosis of cardiomyocyte by TUNEL staining. Compared with sham mice, TUNEL positive cells were increased in myocardium of MI mice. BDNF markedly inhibited the apoptosis of cardiomyocytes (Fig. 5D, E). Moreover, we detected mRNA level of caspase-3 and Bcl-2 and found that caspase-3 was downregulated while Bcl-2 was upregulated by BDNF (Fig. 6A, B). Meanwhile, protein expression of Bcl-2 was increased and caspase-3 activity was decreased in BDNF treated mice (Fig. 6C, D). These data suggested that BDNF inhibited ischemic-induced apoptosis in cardiomyocytes. Therefore, our results indicated that BDNF inhibited apoptosis in cardiac ischemic injury.


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)

Effect of BDNF on cardiomyocytes apoptosis in mice 3 days post-MI. (A, B) The mRNA level of Bcl-2 and caspase-3. (C) Representative bands of protein expression of Bcl-2. (D) Caspase-3 activity. *p<0.05 vs. sham, #p<0.05 vs. MI, n = 4 mice each group.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 6: Effect of BDNF on cardiomyocytes apoptosis in mice 3 days post-MI. (A, B) The mRNA level of Bcl-2 and caspase-3. (C) Representative bands of protein expression of Bcl-2. (D) Caspase-3 activity. *p<0.05 vs. sham, #p<0.05 vs. MI, n = 4 mice each group.
Mentions: We further examined the apoptosis of cardiomyocyte by TUNEL staining. Compared with sham mice, TUNEL positive cells were increased in myocardium of MI mice. BDNF markedly inhibited the apoptosis of cardiomyocytes (Fig. 5D, E). Moreover, we detected mRNA level of caspase-3 and Bcl-2 and found that caspase-3 was downregulated while Bcl-2 was upregulated by BDNF (Fig. 6A, B). Meanwhile, protein expression of Bcl-2 was increased and caspase-3 activity was decreased in BDNF treated mice (Fig. 6C, D). These data suggested that BDNF inhibited ischemic-induced apoptosis in cardiomyocytes. Therefore, our results indicated that BDNF inhibited apoptosis in cardiac ischemic injury.

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