Atrial fibrillation is associated with atrial remodeling, in which connexin 43 (Cx43) and cell hypertrophy play important roles. In this study, apelin-13, an aliphatic peptide, was used to explore the protective effects of the adenosine monophosphate-activated protein kinase (AMPK)/mTOR signaling pathway on Cx43 expression and autophagy, using murine atrial HL-1 cells. The expression of Cx43, AMPK, B-type natriuretic peptide (BNP) and pathway-related proteins was detected by Western blot analysis. Cellular fluorescence imaging was used to visualize Cx43 distribution and the cytoskeleton. Our results showed that the Cx43 expression was significantly decreased in HL-1 cells treated with angiotensin II but increased in cells additionally treated with apelin-13. Meanwhile, apelin-13 decreased BNP expression and increased AMPK expression. However, the expression of Cx43 and LC3 increased by apelin-13 was inhibited by treatment with compound C, an AMPK inhibitor. In addition, rapamycin, an mTOR inhibitor, promoted the development of autophagy, further inhibited the protective effect on Cx43 expression and increased cell hypertrophy. Thus, apelin-13 enhances Cx43 expression and autophagy via the AMPK/mTOR signaling pathway, and serving as a potential therapeutic target for atrial fibrillation.

• MeSH
• angiotensin II farmakologie   MeSH
• autofagie účinky léků   MeSH
• buněčné linie MeSH
• down regulace účinky léků   MeSH
• fibrilace síní metabolismus   patologie   prevence a kontrola   MeSH
• kardiomyocyty účinky léků   metabolismus   patologie   MeSH
• konexin 43 metabolismus   MeSH
• lékové interakce MeSH
• mezibuněčné signální peptidy a proteiny farmakologie   MeSH
• myši MeSH
• proteinkinasy aktivované AMP metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• TOR serin-threoninkinasy metabolismus   MeSH
• vazokonstriktory farmakologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Erythropoietin (EPO), known for its role in erythroid differentiation, has been suggested to have a direct protective role against a variety of neurotoxic insults. In the present study, we investigated the expression of EPO receptor (EPOR) and the number of EPORpositive cells in three encephalic regions (ventral mesencephalon, striatum, cortex) following lesion induced by 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP). C57BL/6 mice underwent intraperitoneal injection of MPTP at 24 h intervals for 5 days, and their brains were examined 1, 2, 4, 7, 14 or 21 days after the last injection. Western blot and immunohistochemistry analysis revealed that EPOR was dramatically up-regulated in the ventral mesencephalon, 4 days after MPTP insult until the day 21. In contrast, there was a baseline level of EPOR in the striatum and cortex. At subsequent time points after MPTP injury, the levels of EPOR in the two regions were not statistically different compared with those in normal animals. These results suggest that the regional specific up-regulation of EPOR at an early stage after MPTP stimulus may represent a pro-survival mechanism against neurotoxin injury in Parkinsonian model.

• MeSH
• corpus striatum metabolismus   MeSH
• financování organizované MeSH
• imunohistochemie MeSH
• modely nemocí na zvířatech MeSH
• mozková kůra metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• parkinsonské poruchy metabolismus   MeSH
• receptory erythropoetinu metabolismus   MeSH
• substantia nigra metabolismus   MeSH
• upregulace fyziologie   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH

• Publikační typ
• abstrakt z konference MeSH