Oleate prevents palmitate-induced cytotoxic stress in cardiac myocytes
Oleate prevents palmitate-induced cytotoxic stress in cardiac myocytes
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DOI：
10.1016/j.bbrc.2005.08.088
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发表时间：
2005-10-14
影响因子：
3.1
通讯作者：
Sawyer, DB
中科院分区：
文献类型：
--
作者：
Miller, TA;LeBrasseur, NK;Sawyer, DB
饱和脂肪酸的细胞毒性与心血管疾病的病理生理学有关，但其对心肌细胞的影响尚不完全清楚。我们研究了棕榈酸酯和单不饱和脂肪酸油酸酯对新生大鼠心室肌细胞生物学的影响。棕榈酸（0.5 mM）增加氧化应激，以及激活的应激相关蛋白激酶（SAPK）p38，Erk 1/2，和JNK，18小时后，诱导细胞凋亡，在24小时后，在类似的20%。抗氧化剂和SAPK抑制剂都不能阻止棕榈酸诱导的细胞凋亡。低浓度的油酸酯（0.1 mM）完全抑制棕榈酸酯诱导的氧化应激，SAPK激活和细胞凋亡。增加线粒体摄取的棕榈酸与L-肉毒碱减少细胞凋亡，而减少摄取的肉毒碱棕榈酰转移酶-1抑制剂perhexiline几乎增加了一倍棕榈酸诱导的细胞凋亡。这些结果支持棕榈酸诱导的细胞凋亡，激活SAPKs，和蛋白质氧化应激的模型，涉及饱和脂肪酸的胞质积累的心肌细胞。(c)2005年爱思唯尔公司All rights reserved.
The cytotoxicity of saturated fatty acids has been implicated in the pathophysiology of cardiovascular disease, though their effects on cardiac myocytes are incompletely understood. We examined the effects of palmitate and the mono-unsaturated fatty acid oleate on neonatal rat ventricular myocyte cell biology. Palmitate (0.5 mM) increased oxidative stress, as well as activation of the stress-associated protein kinases (SAPK) p38, Erk1/2, and JNK, following 18 h and induced apoptosis in similar to 20% of cells after 24 h. Neither antioxidants nor SAPK inhibitors prevented palmitate-induced apoptosis. Low concentrations of oleate (0.1 mM) completely inhibited palmitate-induced oxidative stress, SAPK activation, and apoptosis. Increasing mitochondrial uptake of palmitate with L-carnitine decreased apoptosis, while decreasing uptake with the carnitine palmitoyl transferase-1 inhibitor perhexiline nearly doubled palmitate-induced apoptosis. These results support a model for palmitate-induced apoptosis, activation of SAPKs, and protein oxidative stress in myocytes that involves cytosolic accumulation of saturated fatty acids. (c) 2005 Elsevier Inc. All rights reserved.