Remote limb preconditioning protects against ischemia-induced neuronal death through ameliorating neuronal oxidative DNA damage and parthanatos.
Remote limb preconditioning (RPC) ameliorates ischemia-induced cerebral infarction and promotes neurological function recovery; however, the mechanism of RPC hasn't been fully understood, which limits its clinical application. The present study aimed at exploring the underlying mechanism of RPC through testing its effects on neuronal oxidative DNA damage and parthanatos in a rat focal cerebral ischemia model. Infarct volume was investigated by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, and neuronal survival was evaluated by Nissl staining. Oxidative DNA damage was investigated via analyzing the expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Besides, terminal deoxynucleotidyl transferase-mediated biotinylated-dUTP nick-end labeling (TUNEL) and DNA laddering were utilized to evaluate neuronal DNA fragmentation. Moreover, we tested whether RPC regulated poly(ADP-ribose) polymer (PAR) and apoptosis inducing factor (AIF) pathway; thus, PAR expression, AIF translocation and AIF/histone H2AX (H2AX) interaction were investigated. The results showed that RPC exerted neuroprotective effects by ameliorating oxidative DNA damage and neuronal parthanatos; additionally, RPC suppressed PAR/AIF pathway through reducing AIF translocation and AIF/H2AX interaction. The present study further exposed neuroprotective mechanism of RPC, and provided new evidence for the research on RPC and ICS.
Department of Neurology, Shanghai No. 5 hospital, Fudan University, Shanghai, China.
Wei
W
Jin
Department of Neurology, Shanghai No. 5 hospital, Fudan University, Shanghai, China.
Wei
W
Xu
Department of Neurology, Shanghai No. 5 hospital, Fudan University, Shanghai, China.
Jing
J
Chen
Department of Neurology, Shanghai No. 5 hospital, Fudan University, Shanghai, China.
Xiaoxiao
X
Zhang
Department of Neurology, Shanghai No. 5 hospital, Fudan University, Shanghai, China. Electronic address: leishistone@sina.com.
Lei
L
Shi
Department of Neurology, Shanghai No. 5 hospital, Fudan University, Shanghai, China. Electronic address: rccnsf@sina.com.
Chuancheng
C
Ren
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death / Q000502:physiology; D002544:Cerebral Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D005121:Extremities / Q000098:blood supply*; D005263:Femoral Artery; D006657:Histones / Q000378:metabolism; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D000066829:Neuroprotection; D018384:Oxidative Stress / Q000502:physiology; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
D051033:Apoptosis Inducing Factor; D006657:Histones; D011064:Poly Adenosine Diphosphate Ribose; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine
Apoptosis inducing factor; Cerebral ischemia; DNA damage; Parthanatos; Poly(ADP-ribose) polymer; Remote limb preconditioning