Calpain inhibitors reduce depolarization induced loss of tau protein in primary septo-hippocampal cultures.
We studied the effects of a 6-min potassium depolarization injury produced by 60 mM KCl and 1.8 mM or 5.8 mM extracellular CaCl2 on tau protein levels in primary rat septo-hippocampal cultures. One day after injury, Western blot analyses revealed a calcium dependent loss of tau protein of approximately 50% of control values. Loss of tau protein was associated with calpain 1 mediated breakdown products to alpha-spectrin. Calpain inhibitors 1 and 2, applied immediately after depolarization injury and available to cultures for 24 h reduced depolarization induced degradation of tau protein to approximately 35% or 25% of control values, respectively. We propose that brief potassium depolarization causes degradation of tau protein, possibly due to calpain activation. Thus, calpain inhibitors could represent a viable strategy for preserving the cytoskeletal structure of injured neurons.
D000818:Animals; D015153:Blotting, Western; D002122:Calcium Chloride / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006023:Glycoproteins / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D016875:tau Proteins / Q000096:biosynthesis* / Q000187:drug effects*
D006023:Glycoproteins; C039304:calpain inhibitors; D016875:tau Proteins; D002122:Calcium Chloride; D011188:Potassium