Distinct glycosylation in membrane proteins within neonatal versus adult myocardial tissue

Distinct glycosylation in membrane proteins within neonatal versus adult myocardial tissue
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DOI:
10.1016/j.matbio.2019.05.001
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发表时间:
2020-01-01
期刊:
影响因子:
6.9
通讯作者:
Pandit, Abhay
Pandit, Abhay
中科院分区:
生物学1区
文献类型:
--
作者:
Contessotto, Paolo;Ellis, Bradley W.;Pandit, Abhay

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哺乳动物心脏的再生潜力仅限于新生儿早期,并在出生后7天内丧失。新生儿心脏组织特有的碳水化合物可能是再生潜力的关键调节因子。虽然细胞表面和细胞外基质糖基化是已知的组织和细胞功能和发育的调节剂,但是从新生组织到成熟的心脏糖基化的变化还没有被充分研究。使用凝集素组织化学和微阵列分析,右心室或左心室的糖基化之间也没有任何差异。然而,在Sprague-Dawley品系中,使用质谱分析,左心室中的新生儿心脏糖基化与成人组织不同,显示在三天大的新生儿组织中高甘露糖结构的表达较高,而复杂N-连接聚糖的表达较低。Man(6)GlcNAc(2)被确定为主要的高甘露糖N-连接结构,其在成人中减少,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。在成人中,粘蛋白核心2型O-连接聚糖的出现减少,在新生儿组织中鉴定出一种硫酸化核心2型O-连接结构。有趣的是,来自成熟组织的O-连接聚糖含有N-乙酰神经氨酸(Neu 5Ac)和N-羟乙酰神经氨酸(Neu 5Gc),而所有检测到的唾液酸化N-连接聚糖仅含有Neu 5Ac。由于聚糖与细胞内通讯有关,所发现的特定新生结构可能表明糖基化在哺乳动物心脏新生相关再生能力中的作用。靶向组织糖基化的新策略可能是在心肌梗死等病理情况下实现哺乳动物心脏有效再生的关键因素。(C)2019作者(S)由爱思唯尔公司出版
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. Man(6)GlcNAc(2) 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. (C) 2019 The Author(s). Published by Elsevier B.V.