Pyridoxamine Reverts Methylglyoxal-induced Impairment of Survival Pathways During Heart Ischemia

被引：20

作者：

Almeida, Filipa ^{[1
,2
]}

Santos-Silva, Daniela ^{[1
]}

Rodrigues, Tiago ^{[1
]}

Matafome, Paulo ^{[1
,3
]}

Crisostomo, Joana ^{[1
]}

Sena, Cristina ^{[1
]}

Goncalves, Lino ^{[2
,4
]}

Seica, Raquel ^{[1
]}

机构：

[1] Univ Coimbra, Fac Med, Inst Biomed Imaging & Life Sci IBILI, Physiol Lab, P-3000354 Coimbra, Portugal

[2] Univ Coimbra, Fac Med, IBILI, Basic Res Unit Cardiol, P-3000354 Coimbra, Portugal

[3] Univ Coimbra, Fac Med, Ctr Ophthalmol, IBILI, P-3000354 Coimbra, Portugal

[4] Univ Coimbra, Ctr Hosp, Dept Cardiol, P-3000354 Coimbra, Portugal

来源：

CARDIOVASCULAR THERAPEUTICS | 2013年 / 31卷 / 06期

关键词：

AGE; Diabetes; Heart ischemia; Methylglyoxal; Pyridoxamine; GLYCATION END-PRODUCTS; CARDIAC ISCHEMIA; OXIDATIVE STRESS; APOPTOSIS; AKT; REACTIVATION; INHIBITION; ACTIVATION; INJURY;

D O I：

10.1111/1755-5922.12039

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background and aimsIncreased levels of advanced glycation end-products (AGE) and their precursors, such as methylglyoxal (MG), in patients with diabetes may account for impaired response to heart ischemia. Pyridoxamine is a derivate of vitamin B6, which has been shown to reduce AGE formation. Our goal was to assess the role of pyridoxamine in protecting from MG-induced impaired heart response to ischemia. MethodsWistar rats were subjected to MG administration (WM), MG plus pyridoxamine (WMPyr), or no treatment (W). Half of the hearts from each group were submitted to ischemia and the other half were perfused as control. The levels of CEL, Bcl-2, Bax, and total and phosphorylated forms of JNK and Akt were determined. ResultsMethylglyoxal led to higher levels of AGE and AGE receptor (RAGE) than in the W group. During ischemia, MG caused an impairment of survival pathways and Bcl-2/Bax ratio, a marker of apoptosis. Pyridoxamine treatment decreased glycation and restored the activation of JNK and Akt during ischemia. These events were followed by levels of Bcl-2/Bax ratio similar to W group. ConclusionMethylglyoxal-induced AGE accumulation impairs the activation of cell survival pathways during ischemia. Pyridoxamine-induced decrease of glycation inhibited the effects of MG accumulation in the heart, suggesting that it can be of added value to usual diabetic therapy.

引用

页码：E79 / E85

页数：7

共 33 条

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