Department of Morphological Sciences, Warsaw University of Life Sciences-SGGW, Nowoursynowska 159, 02-776 Warsaw, Poland.
Department of Physiological Sciences, Warsaw University of Life Sciences-SGGW, Nowoursynowska 159, 02-776 Warsaw, Poland.
Int J Mol Sci. 2019 Apr 27;20(9):2085. doi: 10.3390/ijms20092085.
Tumor cells possess a high metabolic plasticity, which drives them to switch on the anaerobic glycolysis and lactate production when challenged by hypoxia. Among the enzymes mediating this plasticity through bidirectional conversion of pyruvate and lactate, the lactate dehydrogenase A (LDHA) and lactate dehydrogenase B (LDHB), are indicated. LDHA has a higher affinity for pyruvate, preferentially converting pyruvate to lactate, and NADH to NAD in anaerobic conditions, whereas LDHB possess a higher affinity for lactate, preferentially converting lactate to pyruvate, and NAD to NADH, when oxygen is abundant. Apart from the undisputed role of LDHA and LDHB in tumor cell metabolism and adaptation to unfavorable environmental or cellular conditions, these enzymes participate in the regulation of cell death. This review presents the latest progress made in this area on the roles of LDHA and LDHB in apoptosis and autophagy of tumor cells. Several examples of how LDHA and LDHB impact on these processes, as well as possible molecular mechanisms, will be discussed in this article. The information included in this review points to the legitimacy of modulating LDHA and/or LDHB to target tumor cells in the context of human and veterinary medicine.
肿瘤细胞具有很高的代谢可塑性，当受到缺氧的挑战时，它们会启动无氧糖酵解和乳酸生成。在介导这种可塑性的酶中，通过丙酮酸和乳酸的双向转化，乳酸脱氢酶 A（LDHA）和乳酸脱氢酶 B（LDHB）被指出。LDHA 对丙酮酸具有更高的亲和力，在无氧条件下优先将丙酮酸转化为乳酸，并将 NADH 转化为 NAD，而 LDHB 对乳酸具有更高的亲和力，在氧充足时优先将乳酸转化为丙酮酸，并将 NAD 转化为 NADH。除了 LDHA 和 LDHB 在肿瘤细胞代谢和适应不利环境或细胞条件方面的无可争议的作用外，这些酶还参与细胞死亡的调节。这篇综述介绍了在 LDHA 和 LDHB 在肿瘤细胞凋亡和自噬中的作用方面取得的最新进展。本文将讨论 LDHA 和 LDHB 如何影响这些过程的几个例子，以及可能的分子机制。这篇综述中包含的信息表明，在人类和兽医医学的背景下，调节 LDHA 和/或 LDHB 以靶向肿瘤细胞是合理的。
