Disease relevance of LDHB

• These increases were accompanied with a decrease of LDH-H and an increase of LDH-M in serum from newborns and patients with ovarian cancer, while an increase of LDH-H in serum from patients with myocardial infarction was dominant [1].
• Our data are the first to show loss of LDHB expression in prostate cancer, the mechanism of which appears to involve promoter hypermethylation [2].
• The human LDH-A and LDH-B cDNAs, containing the coding regions for the L-lactate dehydrogenase A4 (M) and B4 (H) polypeptides respectively have been cloned into Escherichia coli to place the cDNAs under the control of hybrid E. coli/Bacillus stearothermophilus transcriptional and translational signals [3].
• Structure and sequence conservation of a putative hypoxia response element in the lactate dehydrogenase-B gene of Fundulus [4].
• None of the patients without lymph node metastases were diagnosed as TRG 5 [5].

High impact information on LDHB

• Physiological basis for swimming endurance differences between LDH-B genotypes of Fundulus heteroclitus [6].
• At 25 degrees C there were no differences between LDH-B phenotypes in erythrocyte adenosine triphosphate levels, blood oxygen affinity, or swimming performance [6].
• Since oxygen delivery to muscle affects swimming performance, fish of each homozygous LDH-B phenotype were swum to exhaustion at 10 degrees or 25 degrees C to determine whether in vitro differences attributed to the LDH-B allelic isozymes were manifest in vivo [6].
• Adaptive variation in lactate dehydrogenase-B gene expression: role of a stress-responsive regulatory element [7].
• To test the hypothesis that this element is involved in the variation between populations of F. heteroclitus, we exposed transiently transgenic fish containing Ldh-B regulatory sequence/reporter gene constructs to handling stress or injected cortisol [7].

Biological context of LDHB

• The structural gene LDHA has been previously assigned to human chromosome 11, while LDHB maps to chromosome 12 [8].
• Chromosomes 1, 2, 4, 9, and 10 appear to contain LDHA gene-related sequences, whereas the X chromosome and chromosome 13 possess LDHB gene-related sequences [9].
• The demonstration of a dosage effect for four enzymes--TPI, GAPHD, LDHB, and ENO2--in the infant's erythrocytes was consistent with trisomy 12p [10].
• 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 [11].
• The nucleotide and amino acid sequences of the human LDH-B coding region show 68% and 75% homologies respectively with those of the human LDH-A [12].

Anatomical context of LDHB

• LDHA and LDHB are expressed in most somatic tissues, while expression of LDHC is confined to the germinal epithelium of the testes [8].
• In contrast, LDH-A and LDH-B were ubiquitously expressed in normal and tumor tissues, with LDH-B levels considerably lower and heterogeneous in normal samples compared to those expressed in tumor cell lines [13].
• This interpretation was confirmed by a decreased concentration of the LDH-B subunit in lactate dehydrogenase isozymes of the patient's fibroblasts, consistent with his being hemizygous for the LDHB locus [14].
• In lymphocyte cultures 9% of the cells had either no or two rings, but the patient's RBC had normal activities of the enzymes lactate dehydrogenase B and peptidase B, whose loci are located on the proximal portions of 12p and 12q, respectively [15].
• Approximately one third of the Ldh-B proximal promoter contains interspersed regions that are functionally important: (1) they bind transcription factors in vivo, (2) they effect a change in transcription as assayed by transient transfection into two different fish cell lines, and (3) they bind purified transcription factors in vitro [16].

Associations of LDHB with chemical compounds

• A variant of lactate dehydrogenase (LDHB GUA1) was previously identified among the Guaymi Indians of Panama and Costa Rica [17].
• For the oxidation of glyoxylate, K(M) values were 0.18 mM and 0.26 mM for LDHA and LDHB respectively with NAD+ as cofactor [18].
• Neither LDHA nor LDHB utilised glycolate as substrate and NADPH was a poor cofactor with a relative activity less than 3% that of NADH [18].
• We used polyacrylamide gradient gel and silver staining procedures for DCP analysis, and observed abnormal migration patterns in individuals heterozygous for the LDH-B deficiency [19].
• Polymerase chain reaction (PCR)-based DNA sequence analysis of the LDH-B subunit gene revealed a heterozygous nucleotide change: a guanine to adenine substitution in codon 69 (GGG --> GAG) at the third exon of the LDH-B subunit gene that resulted in a glycine to glutamic acid substitution (G69E) [20].

Physical interactions of LDHB

• Within the lactate dehydrogenase-B (LdhB) proximal promoter is a region with multiple in vivo footprinted sites that resembles the binding site for the transcription factor SP1 [21].

Regulatory relationships of LDHB

• CONCLUSIONS: The somatic LDHA in R51 cells is transcriptionally silenced by promoter hypermethylation around exon a, leaving only LDHB to be expressed normally and a testis-specific variant transcript of LDHA containing exon 0 [22].
• Contrary to this, in PBMC of NHL patients prior to therapy TNF-alpha induced a significant decrease ( p<0.05) of LDH-H isotype activity [23].

Other interactions of LDHB

• Expression profiles were consistent with the CESH data and overexpression of EST595078, MRPS35 and LDHB at 12p11.2-p12.1 was detected in most TGCTs [24].
• Studies of pigeon LDH have shown tight linkage between LDHB and LDHC leading to the expectation that these genes would be syntenic in man [8].
• A preliminary account of the properties of recombinant human Glyoxylate reductase (GRHPR), LDHA and LDHB with glyoxylate, and their potential roles in its metabolism [18].
• A genetic study of various enzyme polymorphisms in Pleurodeles waltlii (Urodele amphibian). I. Lactate dehydrogenase-B and glucose-6-phosphate dehydrogenase [25].
• Regional mapping of TPI, LDH-B, and Pep-B on chromosome 12 of man [26].

Analytical, diagnostic and therapeutic context of LDHB

• The predicted sequence of 333 amino acid residues was confirmed by amino acid composition and/or sequence analyses of a total of 185 (56%) residues from tryptic peptides of human LDH-B protein [12].
• These findings were indicative of a partial LDH-B subunit deficiency, which was confirmed in erythrocyte hemolysates by Western blotting [20].
• Immunohistochemistry showed a higher frequency of LDHB expression in benign or non-malignant tissues, 59/ 73 (81%), compared to cancer cases, 3/53 (6%) (P < 0.001) [2].
• In patients after administration of chemotherapy, TNF-alpha in a dose of 100 U/ml induced a significant increase ( p<0.05) of LDH-M isotype activity, but not of LDH-H [23].
• Consistent with observed variation in Ldh-B transcription rate between populations, significant differences in reporter gene activity were driven by flanking regions from northern and southern populations both in cell culture and in vivo [27].

References