Abstract
Thallium is considered as an emergent contaminant owing to its potential use in the superconductor alloys. The monovalent thallium, Tl(I), is highly toxic to the animals as it can affect numerous metabolic processes. Here we observed that Tl(I) decreased protein synthesis and phosphorylated eukaryotic initiation factor 2α. Although Tl(I) has been shown to interact with the sulfhydryl groups of proteins and cause the accumulation of reactive oxygen species, it did not activate endoplasmic reticulum stress. Notably, the level of 60S ribosomal subunit showed significant under-accumulation after the Tl(I) treatment. Given that Tl(I) shares similarities with potassium in terms of the ionic charge and atomic radius, we proposed that Tl(I) occupies certain K+-binding sites and inactivates the ribosomal function. However, we observed neither activation of ribophagy nor acceleration of the proteasomal degradation of 60S subunits. On the contrary, the ribosome synthesis pathway was severely blocked, i.e., the impairment of rRNA processing, deformed nucleoli, and accumulation of 60S subunits in the nucleus were observed. Although p53 remained inactivated, the decreased c-Myc and increased p21 levels indicated the activation of nucleolar stress. Therefore, we proposed that Tl(I) interfered the ribosome synthesis, thus resulting in cell growth inhibition and lethality.
Highlights
Thallium is a natural source of trace element in the earth’s crust, with the concentration usually ranging from 0.3 mg/kg to 0.6 mg/kg
The toxicity from metals usually results in oxidative stress, which originates from the imbalance of reactive oxygen species (ROS) production and the ability of cells to scavenge such molecules
The ROS are important for the regulation of various physiological functions, their excess production damages proteins, nucleic acids, membrane and causes the progression of various diseases, i.e., aging and inflammation.We evaluated the oxidative stress stimulated by Tl(I) and observed the elevated production of ROS at Tl(I) concentrations of 10 and 20 ppm (Fig. 1B,C)
Summary
Thallium is a natural source of trace element in the earth’s crust, with the concentration usually ranging from 0.3 mg/kg to 0.6 mg/kg. A total of 116 magnesium ions and 88 monovalent cations, including sodium and potassium, are found in the large ribosomal subunit from Haloarcula marismortui[15]. The high concentration of Tl(I) inactivates translation, particular destabilizing the 60S subunits[17,18]. Under this situation, the structure of the 60S ribosomal subunit was altered using chymotrypsin as a molecular probe[17]. The 40S and 60S subunits are assembled from a large primary rRNA 47S transcribed by RNA polymerase I. The processing of this rRNA yields the 5.8S, 18S, and 28S rRNA. The impairment of ribosome synthesis induced nucleolar stress, resulting in the cell cycle arrest and apoptosis
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