Abstract

Lysophosphatidic acid (LPA) is a bioactive lipid, which plays an indispensable role in various physiological and pathological processes. Moreover, an elevated level of LPA has been observed in malignancies of different origins and implicated in their progression via modulation of proliferation, apoptosis, invasion and metastasis. Interestingly, few recent reports suggest a pivotal role of LPA-modulated metabolism in oncogenesis of ovarian cancer. However, little is understood regarding the role of LPA in the development and progression of T cell malignancies, which are considered as one of the most challenging neoplasms for clinical management. Additionally, mechanisms underlying the LPA-dependent modulation of glucose metabolism in T cell lymphoma are also not known. Therefore, the present study was undertaken to explore the role of LPA-altered apoptosis and glucose metabolism on the survival of T lymphoma cells. Observations of this investigation suggest that LPA supports survival of T lymphoma cells via altering apoptosis and glucose metabolism through changing the level of reactive species, namely nitric oxide and reactive oxygen species along with expression of various survival and glucose metabolism regulatory molecules, including hypoxia-inducible factor 1-alpha, p53, Bcl2, and glucose transporter 3, hexokinase II, pyruvate kinase muscle isozyme 2, monocarboxylate transporter 1, pyruvate dehydrogenase kinase 1. Taken together‚ the results of the present investigation decipher the novel mechanisms of LPA-mediated survival of T lymphoma cells via modulation of apoptosis and glucose metabolism.

中文翻译：

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溶血磷脂酸通过改变细胞凋亡和葡萄糖代谢来促进T淋巴瘤细胞的存活

摘要

溶血磷脂酸（LPA）是一种生物活性脂质，在各种生理和病理过程中起着不可或缺的作用。此外，已经在不同起源的恶性肿瘤中观察到了升高的LPA水平，并通过调节增殖，凋亡，侵袭和转移来暗示其进展。有趣的是，最近很少有报道表明LPA调节的代谢在卵巢癌的发生中起关键作用。然而，关于LPA在T细胞恶性肿瘤的发生和发展中的作用了解甚少，T细胞恶性肿瘤被认为是临床管理中最具挑战性的肿瘤之一。此外，还不清楚T细胞淋巴瘤中LPA依赖性葡萄糖代谢调节的机制。因此，本研究旨在探讨LPA改变的细胞凋亡和葡萄糖代谢对T淋巴瘤细胞存活的影响。这项研究的观察结果表明，LPA通过改变反应性物种（一氧化氮和反应性氧物种）的水平以及各种生存和葡萄糖代谢调节分子（包括低氧诱导型）的表达来改变细胞凋亡和葡萄糖代谢，从而支持T淋巴瘤细胞的生存。因子1-alpha，p53，Bcl2和葡萄糖转运蛋白3，己糖激酶II，丙酮酸激酶肌肉同工酶2，单羧酸盐转运蛋白1，丙酮酸脱氢酶激酶1通过调节细胞凋亡和葡萄糖代谢来调节T淋巴瘤细胞。