Anat Cell Biol.  2024 Jun;57(2):155-162. 10.5115/acb.24.003.

The underlying mechanism of calcium toxicityinduced autophagic cell death and lysosomal degradation in early stage of cerebral ischemia

• Sengking J
• Mahakkanukrauh P

• KMID: 2556559
• DOI: http://doi.org/10.5115/acb.24.003

Abstract

Cerebral ischemia is the important cause of worldwide disability and mortality, that is one of the obstruction of blood vessels supplying to the brain. In early stage, glutamate excitotoxicity and high level of intracellular calcium (Ca²⁺ ) are the major processes which can promote many downstream signaling involving in neuronal death and brain tissue damaging. Moreover, autophagy, the reusing of damaged cell organelles, is affected in early ischemia. Under ischemic conditions, autophagy plays an important role to maintain energy of the brain and its function. In the other hand, over intracellular Ca²⁺ accumulation triggers excessive autophagic process and lysosomal degradation leading to autophagic process impairment which finally induce neuronal death. This article reviews the association between intracellular Ca²⁺ and autophagic process in acute stage of ischemic stroke.

Keyword

Cerebral ischemia; Calcium toxicity; Autophagy; Lysosomal degradation; Neuronal cell death

Figure

• 

  Fig. 1 The underlying mechanism of anoxic depolarization and glutamate excitotoxicity after acute cerebral ischemia. AMPA, glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors; Ca2+, calcium ion; Cl-, chloride ion; Glu, glutamate; Na+, sodium ion; NMDA, N-methyl-D-aspartate receptor; VDCC, voltage-dependent calcium channels.

• 

  Fig. 2 The underlying mechanism of calcium toxicity induced autophagic cell death and lysosomal degradation related to neuronal cell death. 4-HNE, 4-hydroxynonenal; Akt, protein kinase B; AMPK, 5’ AMP-activated protein kinase; Atg, autophagy related protein; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma 2; BNIP3, Bcl-2 interacting protein 3; Ca2+, calcium ion; CaMKKβ, Ca2+/calmodulin-dependent protein kinase kinase β; CaMKII, Ca2+/calmodulin-dependent protein kinase II; DAMPs, damage-associated molecular patterns; HIF-1, hypoxia-inducible factor 1; Hsp70, heat shock protein 70; LAMP-1, lysosomal associated membrane protein 1; mTOR, mammalian target of rapamycin; nNOS, nitric oxide synthase; NO, nitric oxide; ONOO-, peroxynitrite; PI3K, phosphoinositide 3-kinase; TNFR, tumor necrosis factor receptor; ULK1, UNC-51-like kinase 1; VSP34, phosphatidylinositol 3-kinase VPS34 complex; NMDA, N-methyl-D-aspartate receptor; VDCC, voltage-dependent calcium channels; LC3, light chain 3.

Reference

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