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Background: Cell stress and tissue injury lead to c-Jun N-terminal kinase (JNK) activation, which is known to contribute to cell death. Paradoxically, strong evidence supports an important role for JNK in the regeneration of neuronal processes, subsequent to injury. Objective: Recent research revealed the growth cone-associated protein superior cervical ganglion-10 protein as a candidate effector for the regeneration pathway mediated by JNK1. This implies that neuroprotective strategies targeting JNK may have negative effects on neuronal regeneration, unless JNK1 function is spared, and that the mechanistic relationships between JNK1 and neuronal regeneration deserve increased attention. Results: This review proposes a model reconciling the microtubule regulatory properties of superior cervical ganglion protein 10 with its role as a JNK effector of regeneration and highlight remaining issues to be resolved.

Disintegration of nuclear DNA into high molecular weight (HMW) and oligonucleosomal DNA fragments represents two major periodicities of DNA fragmentation during apoptosis. These are thought to originate from the excision of DNA loop domains and from the cleavage of nuclear DNA at the internucleosomal positions, respectively. In this report, we demonstrate that different apoptotic insults induced apoptosis in NB-2a neuroblastoma cells that was invariably accompanied by the formation of HMW DNA fragments of about 50-100 kb but proceeded either with or without oligonucleosomal DNA cleavage, depending on the type of apoptotic inducer. We demonstrate that differences in the pattern of DNA fragmentation were reproducible in a cell-free apoptotic system and develop conditions that allow in vitro separation of the HMW and oligonucleosomal DNA fragmentation activities. In contrast to apoptosis associated with oligonucleosomal DNA fragmentation, the HMW DNA cleavage in apoptotic cells was accompanied by down-regulation of caspase-activated DNase (CAD) and was not affected by z-VAD-fmk, suggesting that the caspase/CAD pathway is not involved in the excision of DNA loop domains. We further demonstrate that nonapoptotic NB-2a cells contain a constitutively present nuclease activity located in the nuclear matrix fraction that possessed the properties of topoisomerase (topo) II and was capable of reproducing the pattern of HMW DNA cleavage that occurred in apoptotic cells. We demonstrate that the early stages of apoptosis induced by different stimuli were accompanied by activation of topo II-mediated HMW DNA cleavage that was reversible after removal of apoptotic inducers, and we present evidence of the involvement of topo II in the formation of HMW DNA fragments at the advanced stages of apoptosis. The results suggest that topo II is involved in caspase-independent excision of DNA loop domains during apoptosis, and this represents an alternative pathway of apoptotic DNA disintegration from CAD-driven caspase-dependent oligonucleosomal DNA cleavage.

The distribution of voltage‐sensitive elevations of the level of Ca2+in untreated SH‐SY5Y cells and cells that had been induced to differentiate with staurosporine was investigated by monitoring fura‐2 fluorescence in cell suspensions, and by using microfluorometry and quantitative fluorescence imaging on cell bodies and on cellular processes. Cell bodies of both types of cells displayed small Ca2+elevations, which were composed of transient and sustained components. Elevations were partially sensitive to the L‐ and N‐channel blockers nifedipine (1 μM) and ω‐conotoxin GVIA (100 nM) respectively. Up to ten times higher Ca2+elevations were observed in varicosities of treated cells than in cell bodies of treated and untreated cells. These elevations were insensitive to compounds known to release Ca2+from intracellular stores. Elevations of Ca2+were sustained, and they were insensitive to 5 pM nifedipine, 100 nM ω‐agatoxin IVA and 100 nM ω‐conotoxin GVIA, and partially sensitive to 2 pM ω‐conotoxin GVIA, indicating predominance of non‐L‐type, non‐N‐type, non‐P‐type channel activity. The intracellular localization of neuropeptide Y, a marker of differentiation in these cells, was also investigated by fluorescence immunocytochemistry. Varicosities of treated cells displayed marked fluorescence when viewed in a confocal microscope. These findings show that the varicosities of staurosporine‐treated cells exhibit some of the functional properties of nerve terminals. The varicosities resemble boutons en passant nerve endings and they seem to express Ca2+channels different from those in the cell body.