title: Bergmann glia utilize active caspase-3 for differentiation.
abstract: Recently, functions associated with caspase have been modified from their well-established role in apoptosis. Although caspases are still regarded as mediators of apoptosis, some of the pro-apoptotic caspases, namely caspase-8, -14 and -3 also regulate differentiation in certain cell types, namely myelomonocytic cells, osteoblasts, skeletal muscle cells, keratinocytes, and T lymphocytes. In the central nervous system, non-apoptotic active caspase-3 expression has been located in proliferating and differentiating neuronal cells of the ventricular zone and external granular layer of the developing cerebellar cortex. We previously demonstrated that active caspase-3 expression was not limited to neuronal cells but also was located in the Bergmann glia of the postnatal cerebellum. In that study, active caspase-3 immunolabeling did not markedly colocalize with Ki67, a proliferation marker, but was present in differentiating Bergmann glia that expressed brain lipid binding protein (BLBP) and thus, by its localization, suggested a role in the differentiation of Bergmann glia. The current study addresses the function of caspase-3 in Bergmann glia development by utilizing a Bergmann glial culture preparation. Inhibition of caspase-3 activity by the peptide inhibitor, DMQD-FMK, increased the number of proliferating precursor glial cells and decreased the number of differentiating Bergmann glia, without significantly altering the non-glial active caspase-3 negative population. The transformation in the developmental state of Bergmann glia occurring after suppression of caspase-3 activity strongly suggests an involvement of this enzyme in promoting differentiation of Bergmann glia.
authors.affiliation: Department of Physiology, Room 5A163, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
authors.forename: Sowmini
authors.initials: S
authors.lastname: Oomman
authors.forename: Howard
authors.initials: H
authors.lastname: Strahlendorf
authors.forename: Janet
authors.initials: J
authors.lastname: Dertien
authors.forename: Jean
authors.initials: J
authors.lastname: Strahlendorf
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006609:High Mobility Group Proteins / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D055758:SOX9 Transcription Factor; D019311:Staurosporine / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D017304:Annexin A5; D004791:Enzyme Inhibitors; D006609:High Mobility Group Proteins; D009419:Nerve Tissue Proteins; D018809:Proliferating Cell Nuclear Antigen; D055758:SOX9 Transcription Factor; D014157:Transcription Factors; D014404:Tubulin; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D019311:Staurosporine