Anatskaia O V, Vinogradov A E
Tsitologiia. 2010;52(1):52-62.
Excessive somatic polyploidy usually accompanies physiologic and pathologic overload and it is generally accepted as a symptom of pathology. At the same time, polyploidy cells exist in most fungal, plant, mollusk, fish, bird and mammalian tissues confirming their great evolutionary success. The secret of this success remains enigmatic. Since transcriptome rearrangements usually start with metabolic flux redistribution, we decided to investigate firstly the effects of polyploidy on cell metabolism. Using multitest approach of modular biology and databases Entrez Gene, RefSeq, GNF SymAtlas, Gene Ontology, KEGG, BioCarta; MsigDb, Reactome, GenMAPP, and HumanCyc, we performed detailed comparison of metabolic genes expression in human and mouse organs with reciprocal pattern of polyploidy (i. e. in the heart and in the liver). Pairwise criss-cross comparison of diploid vs. polyploid organs allowed removing species- and tissue-specific effects. From our results, polyploidy is associated with rearrangements of main metabolic pathways. We found deep depression of mitochondrial processes, features of autophagia, and increased carbohydrate degradation and lipid biosynthesis. Taken together, these changes pointed to the energy and oxygen deprivation. We also found clear indications of enhanced oxidative stress protection. The major of them are triggering of pentose-phosphate pathway, depression of mitochondria-cytoplasm electron shuttles, and impartment of electron flows across 1 (NADH dehydrogenase) and IV (cytochrome c-oxydase) breath complexes. We suggest that all these changes are necessary for the increase in metabolic plasticity and for the protection of replicating DNA from oxidative damage.
体细胞过度多倍体通常伴随着生理和病理负荷，并且通常被认为是病理症状。与此同时，多倍体细胞存在于大多数真菌、植物、软体动物、鱼类、鸟类和哺乳动物组织中，这证实了它们在进化上的巨大成功。这种成功的秘诀仍然是个谜。由于转录组重排通常始于代谢通量的重新分配，我们决定首先研究多倍体对细胞代谢的影响。我们使用模块化生物学的多测试方法以及Entrez Gene、RefSeq、GNF SymAtlas、基因本体论、KEGG、BioCarta、MsigDb、Reactome、GenMAPP和HumanCyc等数据库，对人类和小鼠器官中具有相反多倍体模式（即心脏和肝脏）的代谢基因表达进行了详细比较。二倍体与多倍体器官的成对交叉比较有助于消除物种和组织特异性影响。从我们的结果来看，多倍体与主要代谢途径的重排有关。我们发现线粒体过程深度抑制、自噬特征以及碳水化合物降解和脂质生物合成增加。综合来看，这些变化表明能量和氧气供应不足。我们还发现了氧化应激保护增强的明确迹象。其中主要包括磷酸戊糖途径的激活、线粒体 - 细胞质电子穿梭的抑制以及电子流通过呼吸复合体I（NADH脱氢酶）和IV（细胞色素c氧化酶）的改变。我们认为所有这些变化对于增加代谢可塑性以及保护复制的DNA免受氧化损伤都是必要的。
