Upregulation of Beclin 1 in the ischemic penumbra.
Here we discuss the probable role of autophagy in cerebral ischemia based on our own recent data and the literature. We examined the protein level of Beclin 1 (Bcl-2 interacting protein) and microtubule-associated protein 1 light chain 3 (LC3) which were previously found to promote autophagy. We found a dramatic elevation in Beclin 1 levels and LC3 in the penumbra of rats challenged by cerebral ischemia. We found also that a subpopulation of Beclin 1-upregulating cells is also expressing the active form of caspase-3, and that all Beclin 1 upregulating cells display dense staining of LC3. Neuronal cells that overexpress Beclin 1 may exhibit damaged DNA but without changes in nuclear morphology, which indicates that not all the Beclin 1-upregulating cells are predestined to die. We conclude that the cell death in the penumbra bears a resemblance not only to necrosis, apoptosis, or a compromise between the two, but exhibits also biochemical and morphological characteristics of autophagic cell death. The question that constantly arises, however, is whether autophagic activity in damaged cells is the cause of death or is actually an attempt to prevent it as a part of an endogenous neuroprotective response.
Rami
Abdelhaq
A
Institute of Cellular and Molecular Anatomy (Anatomie III), Dr. Senckenbergische Anatomie, Klinikum der Johann Wolfgang von Goethe-Universität, Franfurt/Main, Germany. Rami@em.uni-frankfurt.de
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D001343:Autophagy / Q000235:genetics; D000071186:Beclin-1; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism; D016923:Cell Death; D002540:Cerebral Cortex / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008954:Models, Biological; D021381:Protein Transport; D051381:Rats; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D015415:Biomarkers; D008869:Microtubule-Associated Proteins; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat