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首页> 外文期刊>Journal of toxicology and environmental health, Part A >Perfluorooctanoic acid induced-developmental cardiotoxicity: Are peroxisome proliferator activated receptor α (PPARα) and Bone Morphorgenic Protein 2 (BMP2) pathways involved?
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Perfluorooctanoic acid induced-developmental cardiotoxicity: Are peroxisome proliferator activated receptor α (PPARα) and Bone Morphorgenic Protein 2 (BMP2) pathways involved?

机译:全氟辛酸诱导型心肌毒性:涉及过氧化物酶体增殖剂活化受体α(PPARα)和骨质形态蛋白2(BMP2)途径吗?

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摘要

Perfluorooctanoic acid (PFOA) is an environmental contaminant known to induce developmental toxicity in animal models through activation of the peroxisome proliferator-activated receptor α (PPARα). Previously, it was demonstrated that in ovo exposure to PFOA induced cardiotoxicity in chicken embryos and hatchlings. To investigate potential PPARα-mediated mechanisms, fertile chicken eggs were injected prior to incubation with WY 14,643, a PPARα agonist. Cardiac morphology and function were evaluated in late-stage embryos and hatchlings. Histologically, unlike PFOA, WY 14,643 did not induce thinning of the right ventricular wall. Via echocardiography, however, WY 14,643 induced effects similar to those of PFOA, including increased left ventricular wall thickness and mass, elevated heart rate, ejection fraction, fractional shortening, and decreased stroke volume. Additionally, to investigate mechanisms associated with early heart development, a separate group of fertile chicken eggs was injected prior to incubation with PFOA or WY 14,643 and in early-stage embryos, gene expression and protein concentration associated with the bone morphogenic protein (BMP2) pathway were determined. Although changes were not statistically consistent among doses, expression of BMP2, Nkx2.5, and GATA4 mRNA in early embryos was altered by PFOA exposure; however, protein concentrations of these targets were not markedly altered by either PFOA or WY 14,643. Protein levels of pSMAD1/5, a transcriptional regulator stimulated by BMPs, were altered by both PFOA and WY 14,643, but in different directions; PFOA reduced cytoplasmic pSMAD1/5, whereas WY 14,643 decreased nuclear pSMAD1/5. Taken together, these data suggest that developmental cardiotoxicity induced by PFOA likely involves both PPARα and BMP2 pathways.
机译:全氟辛酸(PFOA)是一种众所周知的环境污染物,通过激活过氧化物体增殖物激活的受体α(PPARα)诱导动物模型中的发育毒性。以前,据证明,在卵oO暴露于PFOA诱导鸡胚和幼龟的心脏毒性。为了研究潜在的PPARα介导的机制,在与WY14,643孵育PPARα激动剂之前注射肥沃的鸡蛋。在晚期胚胎和幼龟中评估了心脏形态和功能。组织学上,与PFOA不同,WY 14,643没有诱导右心室壁的稀释。然而,通过超声心动图,WY14,643诱导效果与PFOA类似,包括增加左心室壁厚和质量,心率升高,射血分数,分数缩短和下降体积。另外,为了研究与早期心脏发育相关的机制,在与PFOA或WY14,643和与骨形态发生蛋白(BMP2)途径相关的早期胚胎,基因表达和蛋白质浓度之前,注射了一组单独的肥沃鸡蛋。确定了。虽然在剂量中的变化没有统计学上一致,但通过PFOA暴露改变早期胚胎中的BMP2,NKX2.5和GATA4 mRNA的表达;然而,这些靶标的蛋白质浓度没有通过PFOA或WY14,643显着改变。 PFOA和WY 14,643,但在不同方向上改变了PSMAD1 / 5的蛋白质​​水平,是BMPS刺激的转录调节剂; PFOA减少细胞质PSMAD1 / 5,而WY 14,643减少核PSMAD1 / 5。这些数据表明,PFOA诱导的发育心脏毒性可能涉及PPARα和BMP2途径。

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