Metal chelating and anti-radical activity of Salvia officinalis in the ameliorative effects against uranium toxicity.

Uranium is a highly radioactive heavy metal that is toxic to living things. In this study, physiological, cytogenetic, biochemical and anatomical toxicity caused by uranium and the protective role of sage (Salvia officinalis L.) leaf extract against this toxicity were investigated with the help of Allium test. Germination percentage, root length, weight gain, mitotic index (MI), micronucleus (MN) formation, chromosomal aberrations (CAs), superoxide dismutase (SOD) and catalase (CAT) enzyme activities, malondialdehyde (MDA) levels and changes in root meristem cells were used as indicators of toxicity. In the experimental stage, a total of six groups, one of which was the control, were formed. Group I was treated with tap water, while group II and III were treated only with sage (190 mg/L and 380 mg/L). Groups IV, V and VI were germinated with uranyl acetate dihydrate (0.1 mg/mL), uranyl acetate dihydrate + 190 mg/L sage and uranyl acetate dihydrate + 380 mg/L sage, respectively. Allium cepa L. bulbs of each group were germinated for 72 h, and at the end of the period, routine preparation techniques were applied and physiological, cytogenetic, biochemical and anatomical analyzes were performed. As a result, uranium application caused a significant decrease (p < 0.05) in all physiological parameters and MI values. MN, CAs numbers, SOD and CAT enzyme activities and MDA levels increased significantly (p < 0.05) with uranium application. Uranium promoted CAs in the root tip cells in the form of fragment, vagrant chromosome, sticky chromosome, bridge and unequal distribution of chromatin. In addition, it caused anatomical damages such as epidermis cell damage, cortex cell damage and flattened cell nucleus in root tip meristem cells. Sage application together with uranium caused significant (p < 0.05) increases in physiological parameters and MI values and significant decreases in MN, CAs, SOD and CAT activities and MDA levels. In addition, the application of sage resulted in improvement in the severity of anatomical damages induced by uranium. It was determined that the protective role of sage observed for all parameters investigated was even more pronounced at dose of 380 mg/L. The protective role of sage against uranium toxicity is related to its antioxidant activity, and sage has 82.8% metal chelating and 72.9% DPPH removal activity. As a result, uranyl acetate exhibited versatile toxicity in A. cepa, caused cytotoxicity by decreasing the MI rate, and genotoxicity by increasing the frequencies of MN and CAs. And also, Sage acted as a toxicity-reducing agent by displaying a dose-dependent protective role against the toxic effects induced by uranyl acetate.

Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of Unorthodox Kinase Activity.

The UbiB protein kinase-like (PKL) family is widespread, comprising one-quarter of microbial PKLs and five human homologs, yet its biochemical activities remain obscure. COQ8A (ADCK3) is a mammalian UbiB protein associated with ubiquinone (CoQ) biosynthesis and an ataxia (ARCA2) through unclear means. We show that mice lacking COQ8A develop a slowly progressive cerebellar ataxia linked to Purkinje cell dysfunction and mild exercise intolerance, recapitulating ARCA2. Interspecies biochemical analyses show that COQ8A and yeast Coq8p specifically stabilize a CoQ biosynthesis complex through unorthodox PKL functions. Although COQ8 was predicted to be a protein kinase, we demonstrate that it lacks canonical protein kinase activity in trans. Instead, COQ8 has ATPase activity and interacts with lipid CoQ intermediates, functions that are likely conserved across all domains of life. Collectively, our results lend insight into the molecular activities of the ancient UbiB family and elucidate the biochemical underpinnings of a human disease.