Age-dependent inhibition of neuronal protein synthesis by hypothyroidism in the developing rat brain cortex

Neuronal perikarya isolated from developing rat brain cortex were employed for studying the effect of hypothyroidism on RNA and protein synthesis in vitro. Neuronal protein synthesis was inhibited by hypothyroidism during the second week of brain development. Thyroxine treatment in vivo stimulated neuronal protein synthesis in hypothyroid rats. The synthesis of neuronal RNA was depressed by hypothyroidism in 7-day old rats. The inhibition of neuronal protein synthesis due to the lack of thyroid hormaones was restricted to membrane-bound ribosomes. The results suggest that the maturation of the neurone is very sensitive to hormonal imbalance during the critical period of brain development.     

The effects of insulin on choline kinase activity in cultured rat liver cells

The effect of insulin on phosphatidylcholine biosynthesis in cultured rat liver cells was assessed by measuring changes in the activity of the first enzyme in the choline pathway of phosphatidylcholine biosynthesis, choline kinase (ATP: cholinephosphortransferase, EC 2.7.1.32), in the presence or absence of the hormone. Choline kinase specific activity in liver cells incubated for 18 hours in the presence of 10^?7M insulin increased two-fold from 3.4 ± 0.3 nmoles phosphorylcholine formed/min/mg protein to 7.5 ± 0.6 nmoles/min/mg protein. This effect was dose dependent and reversed by the addition of actinomycin D and cycloheximide. It is concluded that the increase in specific activity is due to synthesis of new enzyme rather than activation of existing enzyme.     

Effects of detergents on catalytic activity of human endometase/matrilysin 2, a putative cancer biomarker

Matrix metalloproteinases (MMPs) are a family of hydrolytic enzymes that play significant roles in development, morphogenesis, inflammation, and cancer invasion. Endometase (matrilysin 2 or MMP-26) is a putative early biomarker for human carcinomas. The effects of the ionic and nonionic detergents on catalytic activity of endometase were investigated. The hydrolytic activity of endometase was detergent concentration dependent, exhibiting a bell-shaped curve with its maximum activity near the critical micelle concentration (CMC) of nonionic detergents tested. The effect of Brij-35 on human gelatinase B (MMP-9), matrilysin (MMP-7), and membrane-type 1 MMP (MT1-MMP) was further explored. Their maximum catalysis was observed near the CMC of Brij-35 (∼ 90 μM). Their IC₅₀ values were above the CMC. The inhibition mechanism of MMP-7, MMP-9, and MT1-MMP by Brij-35 was a mixed type as determined by Dixon’s plot; however, the inhibition mechanism of endometase was noncompetitive with a K_i value of 240 μM. The catalytic activities of MMPs are influenced by detergents. Monomer of detergents may activate and stabilize MMPs to enhance catalysis, but micelle of detergents may sequester enzyme and block the substrate binding site to impede catalysis. Under physiological conditions, a lipid or membrane microenvironment may regulate enzymatic activity.     

Effect of adaptation to high-altitude conditions on the circadian rhythm of the epithelial mitotic activity in the convoluted kidney tubules in white rats

It has been established in experiments on 280 white randombred male rats weighing 100-120 g that the lifting of the animals from the valley (820 m above the sea level) to the mountains (3379 m above the sea level) brings about within the first day marked suppression of the mitotic activity of the epithelium of involuted renal tubules. This activity increases beginning from the end of the first week, approaches the control value by the 30th day of adaptation and almost completely returns to normal by the 60th day of the animals' stay in the mountains. The circadian rhythms of the mitotic activity appeared undisturbed and was monophasic in nature.