Alagebrium attenuates methylglyoxal induced oxidative stress and AGE formation in H9C2 cardiac myocytes

详细信息    查看全文

• 作者：Arti Dhar^a ; ^{artidhar@hyderabad.bits-pilani.ac.in" class="auth_mail" title="E-mail the corresponding author} ; Indu Dhar^b ; Audesh Bhat^c ; Kaushik M. Desai^b
• 关键词：Methylglyoxal ; Cardiomyocytes ; Oxidative stress ; Receptor for advanced glycation endproducts ; Alagebrium
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：1 February 2016
• 年：2016
• 卷：146
• 期：Complete
• 页码：8-14
• 全文大小：756 K

文摘

Diabetes mellitus associated cardiovascular complications are a leading cause of morbidity and mortality worldwide. Methylglyoxal (MG) is a reactive ketoaldehyde and a byproduct of glucose metabolism and an inducer of advanced glycation endproducts (AGEs). Alagebrium (ALA) is an AGEs crosslink breaker, however, the effects of ALA on MG levels and its consequences in cultured rat cardiomyocytes are not known. The aim of the present study was to examine the effect of high glucose and MG on cultured rat cardiomyocytes and to investigate whether ALA could prevent any deleterious effects of high glucose and MG in these cells.

Main methods

MG levels were determined by HPLC. The expression of different genes was measured by RT-PCR. Oxidative stress and AGEs formation was determined by DCF probe and immunocytochemistry respectively.

Key findings

High glucose- and MG treated- cardiomyocytes developed a significant increase in MG, and the expression for caspase-3, Bax, RAGE and NF-KB, which were all attenuated after pretreatment with ALA. A significant increase in reactive oxygen species generation and AGEs formation in high glucose- and MG treated- cultured cardiomyocytes was also observed, which was attenuated after pretreatment with ALA.

Significance

ALA may have a preventive role against the deleterious effects of high glucose and MG in the heart. Prevention of dicarbonyl-induced AGEs, by safer and specific scavengers of MG is an attractive therapeutic option.