title: Low-dose radiation prevents type 1 diabetes-induced cardiomyopathy via activation of AKT mediated anti-apoptotic and anti-oxidant effects.
abstract: We investigated whether low-dose radiation (LDR) can prevent late-stage diabetic cardiomyopathy and whether this protection is because of the induction of anti-apoptotic and anti-oxidant pathways. Streptozotocin-induced diabetic C57BL/6J mice were treated with/without whole-body LDR (12.5, 25, or 50 mGy) every 2 days. Twelve weeks after onset of diabetes, cardiomyopathy was diagnosed characterized by significant cardiac dysfunction, hypertrophy and histopathological abnormalities associated with increased oxidative stress and apoptosis, which was prevented by LDR (25 or 50 mGy only). Low-dose radiation-induced cardiac protection also associated with P53 inactivation, enhanced Nrf2 function and improved Akt activation. Next, for the mechanistic study, mouse primary cardiomyocytes were treated with high glucose (33 mmol/l) for 24 hrs and during the last 15 hrs bovine serum albumin-conjugated palmitate (62.5 μmol/l) was added into the medium to mimic diabetes, and cells were treated with LDR (25 mGy) every 6 hrs during the whole process of HG/Pal treatment. Data show that blocking Akt/MDM2/P53 or Akt/Nrf2 pathways with small interfering RNA of akt, mdm2 and nrf2 not only prevented LDR-induced anti-apoptotic and anti-oxidant effects but also prevented LDR-induced suppression on cardiomyocyte hypertrophy and fibrosis against HG/Pal. Low-dose radiation prevented diabetic cardiomyopathy by improving cardiac function and hypertrophic remodelling attributed to Akt/MDM2/P53-mediated anti-apoptotic and Akt/Nrf2-mediated anti-oxidant pathways simultaneously.
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China.|Ruian Center of Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China.|Ruian Center of Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China.
authors.forename: Xiufei
authors.initials: X
authors.lastname: Lin
authors.affiliation: Ruian Center of Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China.
authors.forename: Lechu
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Pathology, the Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Inspection, the Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Dingliang
authors.initials: D
authors.lastname: Qian
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China.|Ruian Center of Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cheng
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China.|Ruian Center of Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China.
authors.forename: Luqing
authors.initials: L
authors.lastname: He
authors.affiliation: Ruian Center of Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China.|Ruian Center of Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000528:radiation effects*; D014408:Biomarkers, Tumor / Q000097:blood; D006332:Cardiomegaly / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications*; D058065:Diabetic Cardiomyopathies / Q000209:etiology / Q000473:pathology / Q000517:prevention & control* / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D005355:Fibrosis; D005947:Glucose / Q000633:toxicity; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy / Q000532:radiotherapy; D008297:Male; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism / Q000528:radiation effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D010168:Palmitates / Q000633:toxicity; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014965:X-Rays
chemical_list: D000975:Antioxidants; D014408:Biomarkers, Tumor; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010168:Palmitates; D016159:Tumor Suppressor Protein p53; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose
keywords: apoptosis; cardiac hypertrophy remodelling; diabetic cardiomyopathy; low-dose radiation; oxidative stress