Anti-TKT (aa 309-455) polyclonal antibody

Although many mechanisms have been proposed for diabetic encephalopathy in type 2 diabetes mellitus (T2DM), the risk factors for cognitive impairment in type 1 diabetes mellitus (T1DM) are less clear. Here, we show that streptozotocin (STZ)-induced T1DM rats showed cognitive impairment in both Y maze and Morris water maze assays, accompanied with D-ribose was significantly increased in blood and urine, in addition to D-glucose. Furthermore, advanced glycation end products (AGE), Tau hyperphosphorylation and neuronal death in the hippocampal CA4/DG region were detected in T1DM rats. The expression and activity of transketolase (TKT), an important enzyme in the pentose shunt, were decreased in the brain, indicating that TKT may be involved in D-ribose metabolism in T1DM. Support for these change was demonstrated by the activation of TKT with benfotiamine (BTMP) treatment. Decreased D-ribose levels but not D-glucose levels; markedly reduced AGE accumulation, Tau hyperphosphorylation, and neuronal death; and improved cognitive ability in T1DM rats were shown after BTMP administration. In clinical investigation, T1DM patients had high D-ribose levels in both urine and serum. Our work suggests that D-ribose is involved in the cognitive impairment in T1DM and may provide a potentially novel target for treating diabetic encephalopathy.

Transketolase genes are key rate-limiting enzymes in the non-oxidative part of the pentose phosphate pathway, which is an important metabolic pathway in ribose-5-phosphate production. Three human transketolase genes have been identified: Transketolase (TKT), transketolase-like gene 1 (TKTL1) and transketolase-like gene 2 (TKTL2). Transketolase genes serve crucial roles in the tumorigenesis, metastasis and outcome of multiple types of cancer. However, the expression levels and prognostic values of transketolase family genes in patients with ovarian cancer remain unclear. The purpose of the study was to analyze the expression level and prognostic significance of transketolase family genes in ovarian cancer. In the present study, the mRNA expression levels of three transketolase genes in ovarian cancer and normal ovarian tissue were compared by Oncomine. The prognostic values of these genes were systemically assessed using the Kaplan-Meier plotter database. In addition, the associations between the mRNA levels of these transketolase genes and the clinicopathological characteristics of patients with ovarian cancer, such as histological subtype, clinical stage, grade, tumor protein p53 (TP53) mutation status and chemotherapy history were studied. The prognostic roles of transketolase genes were also evaluated in a validation dataset. The results demonstrated that TKT and TKTL1 expression in ovarian cancer tissues was elevated compared with that in normal ovarian tissues. In addition, high mRNA expression of the three transketolase genes was identified to be associated with poorer progression-free survival (PFS) in patients with serous ovarian cancer, especially in patients at an advanced stage. TKTL2 was significantly associated with poor overall survival in all patients with ovarian cancer. Additionally, transketolase family genes served a role in predicting PFS in patients with ovarian cancer treated with platinum and/or taxol. High expression of the three transketolase genes was associated with unfavorable PFS in patients with TP53-mutated ovarian cancer, but not in patients with TP53 wild-type ovarian cancer. These results suggested that transketolase family genes may serve important roles in the prognosis of patients with ovarian cancer.