There is no conclusive evidence as regarding the involvement of autophagy in apoptosis, and a causative relationship between autophagy and cell death has not yet been established in full. Nevertheless, observations of cells with autophagic features in areas undergoing apoptosis have led to define an additional type of cell death commonly referred to as autophagic (also known as cytoplasmic cell death or type II cell death), with morphological features somehow different from those of apoptosis . It is not known whether autophagic activity in dying cells actually causes death or whether it simply occurs as a process alongside it. However, in many neurological diseases, in certain neuronal cell death pathways and after neuronal injury, increased numbers of autophagosomes have been detected. We have investigated the role of autophagy in the post-translational cleavage of B-cell lymphoma 2 protein (BCL-2) and, hence, in the regulation of neuronal survival in organotypic cultures of post-natal mouse cerebellum, as a model system to study cell death that occurs during normal CNS development. BCL-2 is one of the more widely investigated anti-apoptotic protein in mammals, and its levels are critical for protecting cells from programmed cell death. By cell transfection studies combined with immunocytochemistry and molecular biology, we report here that the cellular content of BCL-2 is regulated at post-translational level along the autophagy/lysosome pathways in organotypic cultures of post-natal mouse cerebellar cortex. Specifically this mechanism appears to be effective in the cerebellar granule cells (CGCs) that are known to undergo massive apoptosis during post-natal maturation. By the use of specific agonists/antagonist of calcium channels at the endoplasmic reticulum it was possible to understand the pivotal role of calcium release from intracellular stores in CGC neuroprotection.
Intervention of autophagy in the regulation of cerebellar granule cell survival
MERIGHI, Adalberto;LOSSI, Laura
2012-01-01
Abstract
There is no conclusive evidence as regarding the involvement of autophagy in apoptosis, and a causative relationship between autophagy and cell death has not yet been established in full. Nevertheless, observations of cells with autophagic features in areas undergoing apoptosis have led to define an additional type of cell death commonly referred to as autophagic (also known as cytoplasmic cell death or type II cell death), with morphological features somehow different from those of apoptosis . It is not known whether autophagic activity in dying cells actually causes death or whether it simply occurs as a process alongside it. However, in many neurological diseases, in certain neuronal cell death pathways and after neuronal injury, increased numbers of autophagosomes have been detected. We have investigated the role of autophagy in the post-translational cleavage of B-cell lymphoma 2 protein (BCL-2) and, hence, in the regulation of neuronal survival in organotypic cultures of post-natal mouse cerebellum, as a model system to study cell death that occurs during normal CNS development. BCL-2 is one of the more widely investigated anti-apoptotic protein in mammals, and its levels are critical for protecting cells from programmed cell death. By cell transfection studies combined with immunocytochemistry and molecular biology, we report here that the cellular content of BCL-2 is regulated at post-translational level along the autophagy/lysosome pathways in organotypic cultures of post-natal mouse cerebellar cortex. Specifically this mechanism appears to be effective in the cerebellar granule cells (CGCs) that are known to undergo massive apoptosis during post-natal maturation. By the use of specific agonists/antagonist of calcium channels at the endoplasmic reticulum it was possible to understand the pivotal role of calcium release from intracellular stores in CGC neuroprotection.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
