Toxicity of heavy metals: 1. Correlation of metal toxicity with in vitro calmodulin inhibition. 2. Interactions of inorganic mercury with red blood cells: Control vs. amyotrophic lateral sclerosis
The toxic effects of metals are examined in two separate in vitro systems. In the first system, the correlation between published mouse LD{sub 50} values and experimentally derived values for calmodulin inhibition was determined. Calmodulin activity was defined as stimulated phosphodiesterase (PDE) activity. The basal PDE activity was determined with each cation and was unaffected by any of the concentrations utilized. The IC{sub 50} was determined from a plot of the log of the cation concentration vs. stimulated PDE activity for each cation. A very strong correlation was obtained when the IC{sub 50} vs. mouse LD{sub 50} curve was examined (p < 0.001). Calmodulin regulates many enzyme systems and processes that affect or are affected by calcium. This study was examined in light of the possible role of calcium in cell damage and death. In the second study, the interactions of erythrocytes (RBCs) and inorganic mercury (Hg) were examined. A broad range of Hg concentrations were utilized to explore the nature of the interactions. Two different mechanisms of RBC Hg accumulation and retention were evident. At lower Hg concentrations (0.001-0.1 {mu}M), the RBC accumulation/retention of Hg was constant (52% of available Hg), reversible, and temperature sensitive. At higher concentrations (1-100 {mu}M), the accumulation increased with Hg concentration, was not reversible, and was not temperature sensitive. A relationship between Hg and amyotrophic lateral sclerosis (ALS) is suggested by several reports in the literature. The accumulation/ retention of Hg by RBCs from control and ALS patients were compared. The RBCs from ALS patients released far more Hg during a two hr incubation 37C at 10 and 100 {mu}M Hg compared to controls.
- Research Organization:
- Kentucky Univ., Lexington, KY (United States)
- OSTI ID:
- 5472505
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
Similar Records
Apparent segregation distortion for the SOD1 mutation in amyotrophic lateral sclerosis
Modulation of insulin responses in cultured cells by calmodulin
Related Subjects
CALCIUM
BIOLOGICAL FUNCTIONS
CALMODULIN
INHIBITION
MERCURY
METABOLISM
METALS
TOXICITY
ENZYME ACTIVITY
ERYTHROCYTES
PHOSPHODIESTERASES
VASCULAR DISEASES
ALKALINE EARTH METALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
DISEASES
ELEMENTS
ENZYMES
ESTERASES
HYDROLASES
MATERIALS
ORGANIC COMPOUNDS
PROTEINS
560300* - Chemicals Metabolism & Toxicology