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Cell Hypertrophy and MEK/ERK Phosphorylation are Regulated by Glyceraldehyde-Derived AGEs in Cardiomyocyte H9c2 Cells

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Abstract

Diabetic cardiomyopathy has been shown to promote hypertrophy, leading to heart failure. Recent studies have reported a correlation between diabetic cardiomyopathy and oxidative stress, suggesting that the accumulation of advanced glycation end products (AGEs) induces the production of reactive oxygen species (ROS). In a clinical setting, AGEs have been shown to increase the risk of cardiovascular disease; however, the relationship between AGEs and cardiac hypertrophy remains unclear. This study sought to identify the role of AGEs in cardiac hypertrophy by treating H9c2 cells with glyceraldehyde-derived AGEs (200 μg/ml) or H2O2 (50 μM) for 96 h. Our results demonstrate that AGEs significantly increased protein levels and cell size. These effects were effectively blocked with PD98059 (10 μM; MEK/ERK inhibitor) pretreatment, suggesting that AGEs caused cell hypertrophy via the MEK/ERK pathway. We then treated cells with AGEs and H2O2 for 0–120 min and employed the Odyssey infrared imaging system to detect MEK/ERK phosphorylation. Our results show that AGEs up-regulated MEK/ERK phosphorylation. However, this effect was blocked by NAC (5 mM; ROS inhibitor), indicating that AGEs regulate MEK/ERK phosphorylation via ROS. Our findings suggest that glyceraldehyde-derived AGEs are closely related to cardiac hypertrophy and further identify a molecular mechanism underlying the promotion of diabetic cardiomyopathy by AGEs.

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Abbreviations

AGEs:

Advanced glycation end products

BSA:

Bovine serum albumin

DCFH-DA:

2′,7′-Dichlorodihydrofluorescein diacetate

DM:

Diabetes mellitus

FBS:

Fetal bovine serum

HBSS:

Hanks balanced salt solution

NAC:

N-acetyl-l-cysteine

ROS:

Reactive oxygen species

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Authors and Affiliations

  1. Department of Bioscience and Technology, Graduate Institute of Medical Science, College of Health Science, Innovate Research Center of Medicine, Chang Jung Christian University, 396 Chang Jung Rd., Sec. 1, Kway Jen, Tainan, Taiwan, ROC

    Shun-Yao Ko

  2. Graduate Institute of Medical Science, College of Health Science, Innovate Research Center of Medicine, Chang Jung Christian University, 396 Chang Jung Rd, Sec. 1, Kway Jen, Tainan, Taiwan, ROC

    I-Hsuan Lin, Hong-I Chen, Tzong-Cherng Chi, Shu-Shing Chang & Yi-Chiang Hsu

  3. Department of Dental Hygiene, China Medical University, Taichung, Taiwan, ROC

    Tzong-Ming Shieh

  4. Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan, ROC

    Hsin-An Ko

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  1. Shun-Yao Ko
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Correspondence to Shun-Yao Ko or Yi-Chiang Hsu.

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Ko, SY., Lin, IH., Shieh, TM. et al. Cell Hypertrophy and MEK/ERK Phosphorylation are Regulated by Glyceraldehyde-Derived AGEs in Cardiomyocyte H9c2 Cells. Cell Biochem Biophys 66, 537–544 (2013). https://doi.org/10.1007/s12013-012-9501-8

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