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Distinct glycosylation in membrane proteins within neonatal versus adult myocardial tissue.
Matrix Biology ( IF 6.9 ) Pub Date : 2019-05-17 , DOI: 10.1016/j.matbio.2019.05.001
Paolo Contessotto 1 , Bradley W Ellis 2 , Chunsheng Jin 3 , Niclas G Karlsson 3 , Pinar Zorlutuna 4 , Michelle Kilcoyne 5 , Abhay Pandit 1
Affiliation  

Mammalian hearts have regenerative potential restricted to early neonatal stage and lost within seven days after birth. Carbohydrates exclusive to cardiac neonatal tissue may be key regulators of regenerative potential. Although cell surface and extracellular matrix glycosylation are known modulators of tissue and cellular function and development, variation in cardiac glycosylation from neonatal tissue to maturation has not been fully examined. In this study, glycosylation of the adult rat cardiac ventricle showed no variability between the two strains analysed, nor were there any differences between the glycosylation of the right or left ventricle using lectin histochemistry and microarray profiling. However, in the Sprague-Dawley strain, neonatal cardiac glycosylation in the left ventricle differed from adult tissues using mass spectrometric analysis, showing a higher expression of high mannose structures and lower expression of complex N-linked glycans in the three-day-old neonatal tissue. Man6GlcNAc2 was identified as the main high mannose N-linked structure that was decreased in adult while higher expression of sialylated N-linked glycans and lower core fucosylation for complex structures were associated with ageing. The occurrence of mucin core type 2 O-linked glycans was reduced in adult and one sulfated core type 2 O-linked structure was identified in neonatal tissue. Interestingly, O-linked glycans from mature tissue contained both N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), while all sialylated N-linked glycans detected contained only Neu5Ac. As glycans are associated with intracellular communication, the specific neonatal structures found may indicate a role for glycosylation in the neonatal associated regenerative capacity of the mammalian heart. New strategies targeting tissue glycosylation could be a key contributor to achieve an effective regeneration of the mammalian heart in pathological scenarios such as myocardial infarction.

中文翻译:

新生儿与成人心肌组织内膜蛋白的明显糖基化作用。

哺乳动物心脏的再生潜能仅限于新生儿早期,并且在出生后7天内丧失。心脏新生儿组织专有的碳水化合物可能是再生潜力的关键调节剂。尽管细胞表面和细胞外基质糖基化是已知的组织以及细胞功能和发育的调节剂,但是从新生儿组织到成熟的心脏糖基化的变化尚未得到充分研究。在这项研究中,成年大鼠心脏心室的糖基化没有显示分析的两个菌株之间的变异性,使用凝集素组织化学和微阵列分析的左右心室的糖基化也没有任何差异。但是,在Sprague-Dawley菌株中,质谱分析表明,左心室的新生儿心脏糖基化不同于成人组织,在三天大的新生儿组织中显示出较高的高甘露糖结构表达和较低的复杂N-连接聚糖表达。Man6GlcNAc2被确定为成年人中降低的主要高甘露糖N-连接结构,而唾液酸化N-连接聚糖的较高表达和复杂结构的较低核心岩藻糖基化与衰老相关。在成年人中,粘蛋白核心2 O型连接的聚糖的出现减少,并且在新生儿组织中鉴定出一种硫酸化核心2 O型连接的结构。有趣的是,来自成熟组织的O-连接聚糖同时含有N-乙酰神经氨酸(Neu5Ac)和N-糖基神经氨酸(Neu5Gc),而所有唾液酸化的N-连接聚糖均仅包含Neu5Ac。由于聚糖与细胞内通讯有关,因此发现的特定新生儿结构可能表明糖基化在哺乳动物心脏的新生儿相关再生能力中的作用。针对组织糖基化的新策略可能是在病理性情况(例如心肌梗塞)中实现哺乳动物心脏有效再生的关键因素。
更新日期:2019-11-18
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