Caspase-1 activity is required for neuronal differentiation of PC12 cells: cross-talk between the caspase and calpain systems.
Previously, we have found that caspase-1 activity is increased during myoblast differentiation to myotubes. Here we show that caspase-1 activity is required for PC12 differentiation to neuronal-like cells. Caspase-1 is shown to be activated (by immunoblotting and by assessing activity in cell extracts) in the PC12 cells following the initial stage of differentiation. The inhibition of caspase-1 arrests PC12 cells at an intermediate stage of differentiation and prevents neurite outgrowth in these cells; the inhibition is reversed upon the removal of the inhibitor. Calpastatin (calpain endogenous specific inhibitor, and a known caspase substrate) is diminished at the later stages of PC12 cell differentiation, and diminution is prevented by caspase-1 inhibition. The degradation of fodrin (a known caspase and calpain substrate) is found in the advanced stage of differentiation. Caspase-1 has been implicated in the activation of proinflammatory cytokines, and in cell apoptosis. The involvement of caspase-1 in two distinct differentiation processes (myoblast fusion and neuronal differentiation of PC12 cells) indicates a function for this caspase in differentiation processes, and suggests some common mechanisms underlying caspase roles in such processes.
Vaisid
T
T
Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, Israel.
Kosower
N S
NS
Barnoy
S
S
D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism*; D061945:Caspase Inhibitors; D002454:Cell Differentiation; D015151:Immunoblotting; D008840:Microfilament Proteins / Q000378:metabolism; D016716:PC12 Cells; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D013049:Spectrin
D002135:Calcium-Binding Proteins; D002154:Calpain; D002352:Carrier Proteins; D020170:Caspase 1; D061945:Caspase Inhibitors; D008840:Microfilament Proteins; D011480:Protease Inhibitors; D013049:Spectrin; C033668:calpastatin