Neurodegeneration induces upregulation of Beclin 1.
Autophagy, a bulk degradation of subcellular constituents, is activated in normal cell growth and development, and represents the major pathway by which the cell maintains a balance between protein synthesis and protein degradation. Autophagy was documented in several neurodegenerative diseases, and under stress conditions the autophagic process can lead to cell death (type II programmed cell death). Beclin 1 is a Bcl-2 interacting protein that was previously found to promote autophagy. We have used Beclin 1 protein as a marker for autophagy following traumatic brain injury in mice. We demonstrated a dramatic elevation in Beclin 1 levels near the injury site. Interestingly Beclin 1 elevation starts at early stages post injury (4 h) in neurons and 3 days later in astrocytes. In both cell types it lasts for at least three weeks. Neuronal cells, but not astrocytes, that overexpress Beclin 1 may exhibit damaged DNA but without changes in nuclear morphology. These observations may indicate that not all the Beclin1 overexpressing cells will die. The elevation of Beclin 1 at the site of injury may represent enhanced autophagy as a mechanism to discard injured cells and reduce damage to cells by disposing of injured components.
Erlich
Shlomit
S
Department of Neurobiochemistry, Tel-Aviv University, Ramat-Aviv, Israel.
Shohami
Esther
E
Pinkas-Kramarski
Ronit
R
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001253:Astrocytes / Q000737:chemistry / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D015415:Biomarkers; D011506:Proteins