ABSTRACT
Protein synthesis is a complex process. Under certain circumstances, abnormal ribosome stalling will occur during translation, resulting in the inability to effectively recover the ribosome for the next round of translation. Nascent polypeptides arisen from the stalled ribosome are at risk of forming aggregate species, and disturbing protein homeostasis and contributing to development of diseases. The ribosome-associated protein quality control(RQC) pathway provides a rescue method for recovering of stalled ribosomes and for proteasomal degradation of nascent polypeptides obstructed on 60S subunits. The latest researches show that there are RQC rescue pathways on the surface of mitochondria (called mitochondrial ribosome-associated protein quality control, mitoRQC). Mitochondria are important organelles involved in energy production and metabolism in eukaryotic cells. More than 98% of mitochondrial proteins are encoded by nuclear genes and transported from the cytoplasm to mitochondria. These proteins are potential targets for mitoRQC, which works synergistically with the internal regulation system of mitochondria to maintain mitochondrial stability. In this review, we will focus on the recent progress on the RQC and mitoRQC pathway as well as their implications in the progression of diseases.
ABSTRACT
<p><b>OBJECTIVE</b>To assess the safety and effects of 40 mg atorvastatin on serum lipids, inflammatory markers and clinical events in ACS patients post PCI.</p><p><b>METHODS</b>A total of 92 patients with ACS post successful PCI were randomly divided into atorvastatin 10 mg/d (group A) and atorvastatin 40 mg/d (group B) on top of the standard medical therapy. Blood were taken at baseline, 4, 12 and 24 weeks for serum alanine aminotransferase (ALT), lipids, high-sensitive C-reactive protein (hs-CRP) and matrix metalloprotease-9 (MMP-9) measurements. The major adverse cardiac events (MACE) were also observed.</p><p><b>RESULTS</b>There was no significant difference in medication withdrawn (2 vs. 3 cases) due to increased ALT (3 times higher than normal) and incidence of MACE (5 vs. 7 cases) between the groups. TC and LDL were significantly reduced in both groups 4 weeks and thereafter post medication compared to pre-treatment (P < 0.05) and the reduction was more significant in group B than that in group A at 24 weeks post medication (P < 0.05) while TG and HDL remained unchanged. hs-CRP was significantly reduced at 12 and 24 weeks in both groups compared to baseline and the reduction was more significant in group B than that in group A at 24 weeks. MMP-9 was significantly reduced in both groups 4 weeks and thereafter post medication compared to pre-treatment (P < 0.05) and the reduction was more significant in group B than that in group A at 12 weeks post medication (P < 0.05).</p><p><b>CONCLUSION</b>Both atorvastatin doses significantly reduced TC, LDL, hs-CRP and MMP-9 in ACS patients post PCI and the reduction was more significant in high dose atorvastatin group at 24 weeks while the MACE and drug withdraw rates were similar between the groups.</p>