Effects of aluminum on neuronal signal transduction: mechanisms underlying disruption of phosphoinositide hydrolysis.
1. Aluminum is neurotoxic in humans and animals and alters formation of inositol phosphate (IP) second messengers following in vivo or in vitro exposure. 2. Several components of the IP signalling system including G-proteins, phosphatidylinositol-specific phospholipase C (PI-PLC), protein kinase C (PKC) and Ca2+ homeostasis are susceptible to inhibition/disruption by aluminum compounds. 3. Recent evidence suggests that, despite its effects on other components, competitive inhibition by aluminum of phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis by PI-PLC underlies its effects on agonist-stimulated IP generation.
Shafer
T J
TJ
Neurotoxicology Division MD-74B, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Mundy
W R
WR
D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D006868:Hydrolysis; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D010716:Phosphatidylinositols; D000535:Aluminum