ABSTRACT
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.
Subject(s)
Apoptosis/physiology , Astrocytes/cytology , Astrocytes/enzymology , Peroxisomes/metabolism , Receptors, Cytoplasmic and Nuclear/metabolism , Thiazolidinediones , Transcription Factors/metabolism , Apoptosis/drug effects , Astrocytes/chemistry , Caspase 3 , Caspases/metabolism , Cell Survival/physiology , DNA Fragmentation , Gene Expression/physiology , Humans , Hypoglycemic Agents/pharmacology , Prostaglandin D2/analogs & derivatives , Prostaglandin D2/pharmacology , RNA, Messenger/analysis , Receptors, Cytoplasmic and Nuclear/analysis , Receptors, Cytoplasmic and Nuclear/genetics , Thiazoles/pharmacology , Transcription Factors/analysis , Transcription Factors/geneticsABSTRACT
A case of malignant lymphoma presented with various neuropsychological symptoms which made it difficult to achieve the diagnosis and therapy. A 9-year-old boy was referred to our hospital with complaints of psychological symptoms, impairment of consciousness and generalized convulsive seizures. A lumbar puncture revealed infiltration of numerous blasts which were positive for immature B cell markers. CT scan showed a mass in the right ethmoidal sinus, but no space occupying lesion in the brain. The tumor cells in the right ethmoidal sinus had the same phenotypes as those in the CSF. Thus a diagnosis of non-Hodgkin's lymphoma, developing in the right ethmoidal sinus and infiltrating into the central nervous system, was established. The blast cells in the liquor and the tumor of the right ethmoidal sinus disappeared after induction of systemic chemotherapy, irradiation and intrathecal chemotherapy. However, intracranial bleeding occurred during the chemotherapy. He died of respiratory failure 10 months after the start of treatment.
