Elevated Phosphate Levels Trigger Autophagy-Mediated Cellular Apoptosis in H9c2 Cardiomyoblasts

Yao Lung Liu, Kuan Ho Lin, Shanmugam Tamilselvi, Wei Kung Chen, Chia Yao Shen, Ray Jade Chen, Cecilia Hsuan Day, Hsi Chin Wu, Vijaya Padma Viswanadha, Chih Yang Huang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background/Aim: In chronic kidney disease (CKD), kidneys fail to maintain phosphorus homeostasis in serum. Elevated phosphorus levels in serum have been associated with cardiovascular diseases in CKD patients and in normal individuals. In this study, we evaluated the level of autophagy- and apoptosis-related markers under different concentrations of hyperphosphate in myocardial cells. Methods: Modulation inflicted on the levels of various survival-, autophagy-, and apoptosis-related markers were determined by Western blotting analysis using total protein extract. FITC-annexin V staining was performed to quantify the apoptotic cells in all groups. Results: Hyperphosphate treatments showed to induce autophagy-related proteins beclin-1, ATG7, and LC3 II through the pAMPK-ULK1 pathway in Western blotting analysis. Further, apoptosis-associated proteins such as Bax, Bid, cytochrome c, and c-caspase-9 were also upregulated with hyperphosphate treatment. 3-Methyladenine, an autophagy inhibitor, inhibited apoptosis significantly in FITC-annexin V staining, and the inhibition of Bax, cytochrome c, and c-caspase-3 was shown by Western blotting. Conclusion: The results suggest that hyperphosphate in H9c2 cardiomyoblasts would lead to cellular apoptosis via autophagy, which is mediated by the pAMPK signaling pathway. Our findings revealed the possible mechanism responsible for the heart damage under hyperphosphatemia.

Original languageEnglish
Pages (from-to)31-40
Number of pages10
JournalCardioRenal Medicine
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

Keywords

  • Apoptosis
  • Autophagy
  • Cardiorenal syndrome
  • Cardiovascular disease
  • Hyperphosphate

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Urology

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