Department of Biophysics, Panjab University, Chandigarh 160014, India.
Mol Cell Biochem. 2012 Dec;371(1-2):115-27. doi: 10.1007/s11010-012-1428-2. Epub 2012 Aug 15.
The lactate dehydrogenase (LDH) has been studied widely because it exists in various isozymic forms. The association of A and B subunits of LDH can generate five tetrameric isozymes, but the finding of the sixth isozyme in mature human testis and sperm indicated the presence of an additional subunit of LDH, designated as LDH-X (also termed LDH-C4 due to tetrameric nature of C-subunit). LDH-C4 isozyme is an iso-, allo-, and auto-antigen present in mammalian sperm cells. The synthesis of LDH-C4 in the testis takes place during sexual maturation, and it is the predominant fraction in mature spermatozoa. Though, originally considered to be testis specific, LDH-C or Ldh3 in mice was later detected in the murine oocyte and early embryo. Ldh3 in mouse supports its role in energy production in spermatids that favor lactate as substrate and in spermatozoa with a characteristic aerobic glycolytic path to yield ATP. During last two decades, cancer/testis-associated genes (CTAs) which are expressed only in the germinal epithelium of the testis are also expressed in some cancer cells, but not in non-cancerous somatic tissues. The CTAs are considered promising candidates for diagnosis and immunotherapy of cancer. The sperm-specific Ldh-c gene has been shown to express in a broad spectrum of human tumors, with high frequency in lung cancer, melanoma, and breast cancer; the protein being expressed virtually in all tumor types tested. Accordingly, LDH-C4 is the unique target for contraception in both males and females and offers potential future for immunotherapy of different types of cancers. As LDH-C has a preference for lactate as a substrate, LDH-C activation in cancer may depend on lactate for ATP production. The major aim of this article is to review the salient features of LDH-C subunit and the immune responses of LDH-C4 in homologous and heterologous species in relation to its role in acceptance or rejection of the allograft and its application in contraception and immunotherapy of cancer, directly or indirectly through the regulation of its substrate, the lactate.
乳酸脱氢酶（LDH）因其存在多种同工酶形式而被广泛研究。LDH 的 A 和 B 亚基的结合可以产生五种四聚体同工酶，但在成熟的人睾丸和精子中发现第六种同工酶表明存在 LDH 的另一个亚基，称为 LDH-X（也称为 LDH-C4，因为 C 亚基的四聚体性质）。LDH-C4 同工酶是哺乳动物精子细胞中的同种型、同种异型和自身抗原。LDH-C4 在睾丸中的合成发生在性成熟期间，它是成熟精子中的主要部分。尽管最初被认为是睾丸特异性的，但后来在小鼠的卵母细胞和早期胚胎中检测到了 LDH-C 或 Ldh3。在精子中，Ldh3 支持其作为乳酸底物的精子细胞中的能量产生的作用，以及具有特征性有氧糖酵解途径以产生 ATP 的精子。在过去的二十年中，仅在睾丸生殖上皮中表达的癌症/睾丸相关基因（CTAs）也在一些癌细胞中表达，但不在非癌性体组织中表达。CTAs 被认为是癌症诊断和免疫治疗的有前途的候选者。已经表明，精子特异性 Ldh-c 基因在广泛的人类肿瘤中表达，在肺癌、黑色素瘤和乳腺癌中频率较高；该蛋白在测试的几乎所有肿瘤类型中都表达。因此，LDH-C4 是男性和女性避孕的独特靶标，并为不同类型癌症的免疫治疗提供了潜在的未来。由于 LDH-C 对乳酸作为底物有偏好，因此癌症中的 LDH-C 激活可能依赖于乳酸来产生 ATP。本文的主要目的是综述 LDH-C 亚基的显著特征及其在同源和异源物种中的免疫反应，以及其在同种异体移植物的接受或排斥中的作用及其在避孕和癌症免疫治疗中的应用，直接或间接地通过调节其底物乳酸。
