Disease relevance of LDHC

• LDHC protein is a biomarker of obstructive (OA) and non-obstructive (NOA) azoospermia in seminal plasma [1], [2].
• Expression of LDHC in tumors is neither mediated by gene promotor demethylation, as previously described for other germ cell-specific genes activated in cancer, nor induced by hypoxia as demonstrated for enzymes of the glycolytic pathway [3].
• Some tumors like meningiomas showed a midzone pattern like increased LDH3 [4].
• In summary, LDH3 activity was elevated in the oliguric stage of Korean hemorrhagic fever and LDH2 was elevated in chronic renal failure; those values were correlated with the BUN level [5].
• LDH 3 was decreased during late pregnancy but increased in severe pre-eclampsia [6].
• Thus, in NHL, LDH-3 seems to be a reliable marker of the presence of the disease in any case, whereas S-LDH is more related to the spread of the lymphoma [7].

Psychiatry related information on LDHC

• Total LDH and isoenzyme LDH-1 were significantly higher, whereas the fractions of LDH-2 and LDH-3 were significantly lower in CJD patients [8].

High impact information on LDHC

• At least two gene duplication events have led to the three lactate dehydrogenase (LDH; EC 1.1.1.27) isozymes (LDH-A, LDH-B, and LDH-C) of chordates [9].
• Sequence analysis of teleost retina-specific lactate dehydrogenase C: evolutionary implications for the vertebrate lactate dehydrogenase gene family [9].
• On the basis of amino acid sequence similarity, we conclude that the LDH-C isozymes in fish and mammals are not orthologous but derive from independent gene duplications [9].
• The sequence and structure of human testis-specific L-lactate dehydrogenase [LDHC4, LDHX; (L)-lactate: NAD+ oxidoreductase, EC 1.1.1.27] has been derived from analysis of a complementary DNA (cDNA) clone comprising the complete protein coding region of the enzyme [10].
• Moreover, we discovered aberrant splicing of LDHC restricted to cancer cells, resulting in four novel tumor-specific variants displaying structural alterations of the catalytic domain [3].

Chemical compound and disease context of LDHC

• LDH-X, an isoenzyme of lactate dehydrogenase specific for germinal epithelium activity, has been measured in the seminal plasma of infertile subjects whose infertility had different origins [11].
• Lactate dehydrogenase (EC 1.1.1.27) isoenzyme LDH-C4 (LDH-X) has been analyzed quantitatively in semen from men with different fertility status, such as men with pregnant wives, men with primary or secondary infertility, volunteers, men taking salazopyrine and men exposed to very hot baths [12].
• The standard semen parameters (sperm concentration and motility and Kruger morphology) and total sperm creatine kinase, HspA2, LDH, and LDH-X activities, and MDA levels were assessed in the control and varicocele groups [13].

Biological context of LDHC

• From the data presented in this report, the human LDHC gene locus is assigned to chromosome 11 [14].
• However, the data presented in this paper show conclusively that LDHC is syntenic with LDHA on human chromosome 11 [14].
• We conclude that the human LDHC promoter contains the necessary regulatory sequence(s) for specific expression of mouse Ldh1 as a transgene during spermatogenesis [15].
• Human testicular lactate dehydrogenase-C gene is interrupted by six introns at positions homologous to those of LDH-A (muscle) and LDH-B (heart) genes [16].
• Ldh3 protein, however, persists to the blastocyst stage of embryonic development localizing mainly to the cortex region of oocytes, eggs, zygotes, and embryonic blastomeres [17].

Anatomical context of LDHC

• The pattern of bands with LDHC hybridization is easily distinguished from the pattern detected by LDHA hybridization, and the LDHC probe is specific for testis mRNA [14].
• A human LDHC cDNA clone was used as a probe to analyze genomic DNA from rodent/human somatic cell hybrids [14].
• Our results indicate that Ldh3 mRNA is transcribed in oocytes and cannot be detected in fertilized eggs [17].
• Testis-specific lactate dehydrogenase (LDH-C4; Ldh3) in murine oocytes and preimplantation embryos [17].
• The human testis-specific lactate dehydrogenase c gene (ldh-c) shows an exceptionally large window of expression throughout pre- and postmeiotic stages of the male germ cell lineage [18].

Associations of LDHC with chemical compounds

• LDHC represents the first lactate dehydrogenase isoform with restriction to tumor cells [3].
• The presence of this element could be involved in regulating ldh-c through the glucocorticoid/androgen pathways at the early stages of ldh-c expression [18].
• The distribution of LDH isozymes in the fetal vitreous and lens homogenate and the near-term neonate aqueous as determined by polyacrylamide disc electrophoresis, was similar to that of the fetal aqueous, LDH-1 and LDH-5 being least and LDH-3 and LDH-4, the highest [19].
• We have analyzed the catalytic properties and subcellular distribution of the lactate dehydrogenase isozyme specific for testis and sperm (LDH X or C4) [20].
• Thiophenoxyacetate, levamisole and dimethyl sulfoxide depressed total LDH and LDH-X was the principal component in the respective patterns for ejaculate concentrates [21].

Other interactions of LDHC

• Locus determining the human sperm-specific lactate dehydrogenase, LDHC, is syntenic with LDHA [14].
• Studies of pigeon LDH have shown tight linkage between LDHB and LDHC leading to the expectation that these genes would be syntenic in man [14].
• TPTE, LDHC, SPO11 were expressed neither in tumor samples nor in healthy tissue [22].
• 1) The Sp1 transcription factor is a testis-"enriched" protein that is absent from most somatic tissues and that appears to play a major role in determining ldh-c expression in the testis [18].
• The UEV3 gene is located on chromosome 11 closely adjacent to TSG101 and LDH-C [23].

Analytical, diagnostic and therapeutic context of LDHC

• Here, we used a combination of gel retardation assays and an in vitro transcription system derived from human tissues to better define the elements that govern ldh-c transcription [18].
• Mean total LDH activity in the CSF was 34.62 +/- 6.52 U/l. Patients with infantile spasms had a lower LDH-1 percentage and higher LDH-3 percentage; the differences from the control group were statistically significant (p < 0.01) [24].
• This was in marked contrast to the LDH isoenzyme pattern observed in the lavage effluent, which showed a lower percent LDH1 and LDH2 and a higher percent LDH3, LDH4, and LDH5 when compared with the corresponding prelavage isoenzyme percentages for serum (unpaired t test, p less than 0.001) [25].
• Human isoenzyme LDH-X (lactate dehydrogenase isoenzyme X) was isolated from seminal fluid of frozen semen samples by affinity chromatography by using oxamate-Sepharose and AMP-Sepharose [26].
• Serum and tumor tissue of a patient with neuroblastoma contained an abnormal isoenzyme of lactate dehydrogenase (LDH; EC 1.1.1.27), which, on agarose gel electrophoresis, migrated between LDH-2 and LDH-3 with a mobility the same as that of the extra LDH isoenzyme found in normal human erythrocytes [27].

References