Huntington disease (HD) is fatal in humans within

Figure 2 and its legend should appear as follows: Figure 2. Spatial distribution of characteristic m/z values for the traumatized, trauma adjacent, and healthy muscle regions. (A) Average peak MALDI mass spectra intensity of primary trauma (tm, red) and trauma adjacent muscle/healthy (hm, tam, blue) region. (B) HE staining of the healthy and the injured soleus muscle in the region of interest are indicated by the red (tm), black (tam), and green (hm) frame. Ion density distributions to the corresponding spectra peak intensity by using (C) supervised approach (ClinProTools) and (D) unsupervised approach (SCiLS Lab). The m/z values 976 and 1488 show significantly lower intensities (p < 0.05) in the primary trauma region (tm) compared to the trauma adjacent (tam) or healthy (hm) muscle regions. In contrast, the m/z values 985 and 1255 exhibited significantly higher intensities (p < 0.05) in the primary trauma region (tm) compared to tam and hm regions. C

Hypoxia is a pro-fibrotic stimulus, which is associated with enhanced collagen synthesis, as well as with augmented collagen prolyl 4-hydroxylase (C-P4H) activity. C-P4H activity is controlled mainly by regulated expression of the ␣ C-P4H subunit.In this study we demonstrate that the increased synthesis of C-P4H-␣(I) protein in human HT1080 fibroblasts under long term hypoxia (36 h, 1% oxygen) is controlled at the translational level. This is mediated by an interaction of RNA-binding protein nucleolin (ϳ64 kDa form) at the 5-and 3-untranslated regions (UTR) of the mRNA. The 5/3-UTR-dependent mechanism elevates the C-P4H-␣(I) expression rate 2.3-fold, and participates in a 5.3-fold increased protein level under long term hypoxia. The interaction of nucleolin at the 5-UTR occurs directly and depends on the existence of an AU-rich element. Statistical evaluation of the ϳ64-kDa nucleolin/RNA interaction studies revealed a core binding sequence, corresponding to UAAAUC or AAAUCU. At the 3-UTR, nucleolin assembles indirectly via protein/protein interaction, with the help of another 3-UTRbinding protein, presumably annexin A2. The increased protein level of the ϳ64-kDa nucleolin under hypoxia can be attributed to an autocatalytic cleavage of a high molecular weight nucleolin form, without alterations in nucleolin mRNA concentration. Thus, the alteration of translational efficiency by nucleolin, which occurs through a hypoxia inducible factor independent pathway, is an important step in C-P4H-␣(I) regulation under hypoxia.