RESUMO
The histidine triad nucleotide binding protein1(HINT1),which belongs to the histidine triad(HIT) enzyme superfamily,exerts its enzymic activities as hydrolase or transferase. Its physiological functions are still unclear. HINT1 protein is expressed in various tissues and plays an important role in transcription and signal transduction. Earlier studies have identified HINT1 as a haplo-insufficient tumor suppressor. Other evidences indicate that HINT1 is involved in a wide variety of physiological processes,some of which are irrelevant with its basic enzymic activities. Investigations recently suggest that HINT1 is closely related to many peripheral and central nervous system diseases,and plays a vital role in some of neuropsychiatric diseases such as inherited peripheral neuropathies,schizophrenia,mood disorder,drug addiction,and Down's syndrome. In this review,the role of HINT1 in above-mentioned neuropsychiatric disorders was summarised,and the research findings of HINT1 in each of the above diseases were summarized and analyzed,in order to provide some guidance for further research on this protein.
RESUMO
Histidine triad nucleotide-binding protein 1 (HINT1) is a member of a superfamily of histidine triad proteins named by the conserved nucleotide-binding motif histidine-x-histidine-x-histidine-xx, in which x represents hydrophobic amino acid. HINT1 is implicated in pathological progress of many human diseases including cancer and schizophrenia; however, little is known about the essential role and pathological consequences of HINT1 in cellular physiology and diseases. Therefore, we summarize the structure, distribution, and physiological function of HINT1 in cells and tissues as well as the correlation between HINT1 and human diseases.
Assuntos
Humanos , Doença , Proteínas do Tecido Nervoso , FisiologiaRESUMO
<p><b>BACKGROUND</b>Both survivin and lung resistance related protein (LRP) are related to the chemoresistances in hepatocellular carcinoma (HCC). But the relationship between survivin and LRP is indefinite. The aim of this study was to investigate the effects of down-regulation of survivin on LRP expressions and the reversal of chemoresistances in HCC both in vitro and in vivo.</p><p><b>METHODS</b>The expressions of survivin were detected by RT-PCR and Western blotting in HCC cell line SMMC-7721 and SMMC-7721/ADM. The sensitivities of these two cell lines to ADM were evaluated by MTT assays. SiRNA which targeted survivin was transfected into SMMC-7721/ADM cells, then the sensitivity of SMMC-7721/ADM cells to ADM and the expressions of survivin and LRP were detected respectively. SMMC-7721/ADM cells were transplanted subcutaneously into nude mice to establish xenograft tumors. Antitumor activities of RNA interference (RNAi) targeting survivin, various doses of ADM and combination therapies were observed respectively. Possible toxicities were evaluated. LRP expression changes were tested. Student's t test was used for evaluating statistical significance.</p><p><b>RESULTS</b>The expressions of survivin in SMMC-7721/ADM cell line showed significant elevation compared to those in SMMC-7721 cell line (P < 0.05). Positive siRNA down-regulated the expressions of survivin significantly (P < 0.05). SiRNA targeting survivin could sensitize SMMC-7721/ADM cells to ADM and down-regulate the expressions of LRP significantly (P < 0.05). Growths of the tumors were significantly inhibited in positive siRNA group as compared with those in the control group from the 8th day (P < 0.05). Combination therapies caused significant tumor inhibitions compared with tumors of nude mice in the other three groups respectively (P < 0.05). No toxicities were found in nude mice treated by siRNA and combination therapies. The expressions of LRP were markedly reduced in tumors treated with siRNA targeting survivin (P < 0.05).</p><p><b>CONCLUSIONS</b>Down regulation of survivin gene by RNAi can increase chemosensitivity of HCC both in vitro and in vivo. The reversal of drug resistance may be reduced through the inhibitions of LRP.</p>