Stress granules in Ciona robusta: First evidences of TIA-1-related nucleolysin and tristetraprolin gene expression under metal exposure.

Stress granules are non-membranous cytoplasmic foci, composed of non-translating messenger ribonucleoproteins, translational initiation factors and other additional proteins. They represent a primary mechanism to rapidly modulate gene expression when cells are subjected to adverse environmental conditions. Very few works have been devoted to study the presence of the molecular components of stress granules in invertebrates. In this work, we characterized the transcript sequences for two important protein components of stress granules, TIA-1-related nucleolysin (TIAR) and tristetraprolin (TTP), in the solitary ascidian Ciona robusta, an invertebrate chordate, and carried out the first studies on their gene expression under stress conditions induced by metals (Cu, Zn and Cd). Data on mRNA expression levels, provided by qRT-PCR analyses, show a generalized decrease at the second day of metal-exposure for both tiar and ttp, suggesting that metal accumulation induces acute stress and the inhibition of the transcription for the two studied proteins. In-situ hybridization analyses demonstrate that TIAR and TTP antisense riboprobes recognize circulating granular amoebocytes in the hemolymph, in both blood lacunae and tunic. The results obtained in this work increase our knowledge on the evolution of anti-stress proteins in metazoans and emphasize the importance of the transcription of tiar and ttp, which represents an efficient physiological response allowing organisms to survive in the environment under stress conditions.

The Expression of Tristetraprolin and Its Relationship with Urinary Proteins in Patients with Diabetic Nephropathy.

OBJECTIVE: Tristetraprolin (TTP), also known as zinc finger protein 36, is an RNA binding protein that has a significant role in regulating the expression of mRNAs containing AU-rich elements. We postulated that TTP might regulate interleukin (IL)-6 and IL-18 expression in diabetes. This study aimed to test the hypothesis that the levels of TTP are correlated with nephropathy in patients with type 2 diabetes. METHODS: Eighty-seven patients (61.3±9.6 years old) who had been diagnosed with type 2 diabetes mellitus and 41 age and sex matched healthy control subjects were enrolled. The diabetes patients were classified into those without proteinuria, with microalbuminuria, and with clinical proteinuria groups according to the ratio of urinary excretion of albumin/creatinine (ACR). RESULTS: Serum and urinary levels of IL-6 and IL-18 were significantly elevated, but those of TTP were significantly decreased in patients with diabetes as compared with control subjects. In addition, serum and urinary levels of IL-6 and IL-18 were significantly higher, but those of TTP were significantly lower in patients with proteinuria than in patients without proteinuria or with microalbuminuria. There was a significant correlation between serum TTP and IL-6/IL-18 (correlation coefficients of -0.572 and -0.685, P < 0.05). CONCLUSION: These results show that diabetes with clinical proteinuria is accompanied by decreased urinary and serum level of TTP and increased levels of IL-6 and IL-18. Decreased TTP expression might occur prior to the increase in IL-6 and IL-18, and decrease of TTP might provide an earlier marker for glomerular dysfunction than IL-6 and IL-18.