Sz. Lin et al., MASTOPARAN-INDUCED APOPTOSIS OF CULTURED CEREBELLAR GRANULE NEURONS IS INITIATED BY CALCIUM-RELEASE FROM INTRACELLULAR STORES, Brain research, 771(2), 1997, pp. 184-195
We have recently reported that mastoparan, a peptide toxin isolated fr
om wasp venom, induces apoptosis in cultured cerebellar granule neuron
s that can be blocked by cholera toxin, an activator of G(s). Measurem
ents of intracellular free calcium concentration ([Ca2+](i)) reveal th
at mastoparan induces a dramatic elevation of [Ca2+](i) that is freque
ntly followed by enhanced leakage of fura-2 out of the neurons, sugges
ting that this rise in [Ca2+](i) may be due to a more generalized chan
ge in membrane permeability. However, the mastoparan-induced initial e
levation of [Ca2+](i) is maintained in the absence of extracellular Ca
2+, suggesting that the rise of [Ca2+](i) is from intracellular stores
. This conclusion is supported by the observation that depletion of [C
a2+](i) stores by pretreatment with either caffeine or thapsigargin at
tenuates both the rise in [Ca2+](i) and cell death induced by mastopar
an, Phospholipase C (PLC) inhibitors, neomycin and U73122 block mastop
aran-induced increases of [Ca2+](i) and protect against neuronal death
. Pretreatment with cholera toxin, but not pertussis toxin, reduced th
e mastoparan-induced rise in [Ca2+](i). Taken together, our data sugge
st that mastoparan initiates cell death in cerebellar granule neurons
by inducing Ca2+ release from intracellular stores, probably via activ
ation of PLC and IP3. A secondary or parallel process results in disru
ption of plasma membrane integrity and may be ultimately responsible f
or the death of these neurons by mastoparan. (C) 1997 Elsevier Science
B.V.