Free Radical Damage in Ischemia-Reperfusion Injury: An Obstacle in Acute Ischemic Stroke after Revascularization Therapy

Figure 1

ROS damage in ischemia-reperfusion injury. First, ROS-generated pathways: MRC; NOX; COX-2; XO. ROS react with DNA and then cause passive DNA damage leading to base modification and SSBs which induce to apoptosis. Reaction of OH⁻ with unsaturated fatty acids generates ROO⁻ which may also cause passive DNA damage. The products of lipid peroxidation such as MDA, HNE, and acrolein can lead to protein dysfunction. Besides, lipid peroxidation increases membrane permeability inducing to mitochondrial swelling. P53 activated by ROS can also cause mitochondrial swelling by MPTP opening via reaction of P53 with Cyp D. P53 induces Cyt C released from mitochondria by reacting with Bcl-2 family proteins and subsequently leads to caspase cascade causing apoptosis. What is more, ROS can activate JNK and p38 MAPK pathways which are activated by ASK1 and lead to apoptosis. MRC: mitochondrial respiratory chain; NOX: NADPH oxidases; COX-2: cyclooxygenase-2; XDH: xanthine dehydrogenase; XO: xanthine oxidase; ROS: reactive oxygen species; SSBs: single-strand breaks; ROO⁻: peroxyl radical; MDA: malondialdehyde; HNE: 4-hydroxynonenal; Cyp D: cyclophilin D; Cyt C: cytochrome C; MPTP: mitochondrial permeability transition pore; ASK1: apoptosis signal-regulating kinase 1; JNK: c-Jun NH2-terminal kinase; p38 MAPK: p38 mitogen-activated protein kinase. “↑” demonstrates events that are increased or enhanced.