Apoptosis

Apoptosis in astrocytic neoplasms
Apoptosis is a form of programmed cell death characterized by specific morphologic and biochemical properties. Tumorgenesis is the consequence not only of cell proliferation but also the loss of the ability to undergo apoptosis [2]. Bcl-2 is a protooncogene which has the ability to block apoptosis in many cell types. Astrocytic neoplasms are very aggressive tumors which many times fail to respond to surgery, radiation or chemotherapy. They frequently overexpress wild-type p53 which is associated with the expression of bcl-2, and thus they may have evolved a mechanism to subvert apoptosis and allow continued growth. We examined the apoptotic index in fifty-nine astrocytic tumors of various histological grades (Oncor ApopTag Plus In Situ Detection Kit) and compared this with the level of bcl-2 expression. Low grade astrocytomas (0.21 +/- 0.05; range 0.0-0.9) and anaplastic astrocytomas (0.27 +/- 0.13; range 0.0-2.6) had significantly less apoptosis than glioblastomas (0.70 +/- 0.13; range 0.0-2.1; Kruskal-Wallis test, P < or = 0.01). In contrast, bcl-2 expression was similar in all grades of astrocytic tumors and did not correlate with the apoptotic index. Cells of low grade and anaplastic astrocytomas are less likely to undergo apoptosis; however, this does not seem to be a direct consequence of the regulation of bcl-2 expression. The difference in growth potential despite differences in apoptotic index is likely to be attributed to differences in mitotic not apoptotic activity.

Carroll RS, Zhang J, Chauncey BW, Chantziara K, Frosch MP, Black PM.  Apoptosis in Astrocytic Neoplasms . Acta Neurochir (Wien), 139(9): 845-850, 1997.



Expression of peroxisome proliferator-activated receptors (PPARS) in human astrocytic cells: PPARgamma agonists as inducers of apoptosis
We report the isolation by RT-PCR of partial cDNAs encoding the human peroxisome proliferator-activated receptor (PPAR) isoforms PPARbeta and -gamma in human primary astrocytes (HPA) as well as in the human malignant astrocytoma cell line T98G. In contrast, we failed to detect PPARalpha mRNA in either of these two cell types. Because PPARbeta is ubiquitously expressed but has, as yet, no known function, we pursued our functional studies of these cells with regard to PPARgamma. To that end, we showed that PPARgamma protein is abundantly expressed in both cell types, having a molecular weight of approximately 50 kDa. Immunocytochemistry revealed a predominantly nuclear localization of this receptor. Moreover, incubation of the two cell types with 1-12 mcM 15-deoxy PGJ(2) or 1-12 mcM ciglitazone, both of which are agonists of PPARgamma, induced loss of cellular viability as assessed by the MTT assay after a 4 hr incubation. Reduced cellular viability as a consequence of exposure to PGJ(2) or ciglitazone resulted from induction of apoptosis, as assessed by DNA fragmentation and Hoechst staining, and involves activation of the CPP32 (caspase-3) protease. These data show that modulation of the process of apoptosis is one function of PPARgamma in cells derived from the human astrocytic lineage. Copyright 2000 Wiley-Liss, Inc.

Chattopadhyay N, Singh DP, Heese O, Godbole M, Sinohara T, Black PM, Brown EM. Expression of Peroxisome Proliferator-Activated Receptors (PPARs) in Human Astrocytic Cells: PPARgamma Agonists as Inducers of Apoptosis . J Neurosci Res, 61(1): 67-74, 2000.z



Apoptosis in tumors of the central nervous system

Imitola J, Nikas D, Black PM. Apoptosis in tumors of the central nervous system. Crit Rev Neurosurg 7: 391-399, 1997.