TY - JOUR
T1 - Active caspase-3 expression during postnatal development of rat cerebellum is not systematically or consistently associated with apoptosis
AU - Oomman, Sowmini
AU - Finckbone, Velvetlee
AU - Dertien, Janet
AU - Attridge, Jennifer
AU - Henne, William
AU - Medina, Margarita
AU - Mansouri, Bobbak
AU - Singh, Hema
AU - Strahlendorf, Howard
AU - Strahlendorf, Jean
PY - 2004/8/16
Y1 - 2004/8/16
N2 - Development is a dynamic process that includes an intricate balance between an increase in cell mass and an elimination of excess or defective cells. Although caspases have been intimately linked to apoptotic events, there are a few reports suggesting that these cysteine proteases can influence the differentiation and proliferation of cells. Specifically, the active form of caspase-3, which has been classified as an executor of apoptosis, recently has been implicated in a nonapoptotic role in the regulation of the cell cycle, cell proliferation, and cell differentiation. This study investigated the nonapoptotic function and phenotypic expression of active caspase-3-positive cells in the external granule cell layer (EGL) of the postnatal rat cerebellum by using biochemical and immunohistochemical analyses, respectively. Evidence that negates an apoptotic function for the caspase-3-positive EGL cells includes a failure to exhibit chromatin condensation (assessed with TOPRO), phosphatidyl serine externalization (Annexin V labeling), or DNA fragmentation (TUNEL labeling). Proliferative (Ki67-positive) and differentiated (TUJ1-positive) cells within the EGL exhibited a cytosolic expression of caspase-3, whereas terminally differentiated granule cells (NeuN-positive) in the internal granular layer and the migrating granule cells did not express active caspase-3. Thus, this study supports a nonapoptotic role for active caspase-3 in cells residing in the EGL and suggests a possible involvement in EGL proliferation and differentiation. £ 2004 Wiley-Liss, Inc.
AB - Development is a dynamic process that includes an intricate balance between an increase in cell mass and an elimination of excess or defective cells. Although caspases have been intimately linked to apoptotic events, there are a few reports suggesting that these cysteine proteases can influence the differentiation and proliferation of cells. Specifically, the active form of caspase-3, which has been classified as an executor of apoptosis, recently has been implicated in a nonapoptotic role in the regulation of the cell cycle, cell proliferation, and cell differentiation. This study investigated the nonapoptotic function and phenotypic expression of active caspase-3-positive cells in the external granule cell layer (EGL) of the postnatal rat cerebellum by using biochemical and immunohistochemical analyses, respectively. Evidence that negates an apoptotic function for the caspase-3-positive EGL cells includes a failure to exhibit chromatin condensation (assessed with TOPRO), phosphatidyl serine externalization (Annexin V labeling), or DNA fragmentation (TUNEL labeling). Proliferative (Ki67-positive) and differentiated (TUJ1-positive) cells within the EGL exhibited a cytosolic expression of caspase-3, whereas terminally differentiated granule cells (NeuN-positive) in the internal granular layer and the migrating granule cells did not express active caspase-3. Thus, this study supports a nonapoptotic role for active caspase-3 in cells residing in the EGL and suggests a possible involvement in EGL proliferation and differentiation. £ 2004 Wiley-Liss, Inc.
KW - Apoptosis
KW - Cell cycle
KW - Development
KW - Differentiation
KW - Granule cells
KW - Proliferation
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U2 - 10.1002/cne.20223
DO - 10.1002/cne.20223
M3 - Article
C2 - 15248196
AN - SCOPUS:3242660745
SN - 0021-9967
VL - 476
SP - 154
EP - 173
JO - Journal of Comparative Neurology
JF - Journal of Comparative Neurology
IS - 2
ER -