title: Blue light emitting diode induces apoptosis in lymphoid cells by stimulating autophagy.
abstract: The present study was performed to examine the induction of apoptotic cell death and autophagy by blue LED irradiation, and the contribution of autophagy to apoptosis in B cell lymphoma A20 and RAMOS cells exposed to blue LED. Irradiation with blue LED reduced cell viability and induced apoptotic cell death, as indicated by exposure of phosphatidylserine on the plasma outside membrane and fragmentation of DNA. Furthermore, the mitochondrial membrane potential increased, and apoptotic proteins (PARP, caspase 3, Bax, and bcl-2) were observed. In addition, the level of intracellular superoxide anion (O2(-)) gradually increased. Interestingly the formation of autophagosomes and level of LC3-II were increased in blue LED-irradiated A20 and RAMOS cells, but inhibited after pretreatment with 3-methyladenine (3-MA), widely used as an autophagy inhibitor. Inhibition of the autophagic process by pretreatment with 3-MA blocked blue LED irradiation-induced caspase-3 activation. Moreover, a significant reduction of both the early and late phases of apoptosis after transfection with ATG5 and beclin 1 siRNAs was shown by the annexin V/PI staining, indicating a crucial role of autophagy in blue LED-induced apoptosis in cells. Additionally, the survival rate of mice irradiated with blue LED after injection with A20 cells increased compared to the control group. Our data demonstrate that blue LED irradiation induces apoptosis via the mitochondrial-mediated pathway, in conjunction with autophagy. Further studies are needed to elucidate the precise mechanism of blue LED-induced immune cell death.
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk 561-712, Republic of Korea.
authors.forename: Phil-Sun
authors.initials: PS
authors.lastname: Oh
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk 561-712, Republic of Korea.
authors.forename: Hyosook
authors.initials: H
authors.lastname: Hwang
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk 561-712, Republic of Korea.
authors.forename: Hwan-Seok
authors.initials: HS
authors.lastname: Jeong
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk 561-712, Republic of Korea.
authors.forename: Jeongil
authors.initials: J
authors.lastname: Kwon
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk 561-712, Republic of Korea.
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk 561-712, Republic of Korea.
authors.forename: Minjoo
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk 561-712, Republic of Korea.
authors.forename: SeokTae
authors.initials: S
authors.lastname: Lim
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk 561-712, Republic of Korea.
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Sohn
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk 561-712, Republic of Korea. Electronic address: jayjeong@jbnu.ac.kr.
authors.forename: Hwan-Jeong
authors.initials: HJ
authors.lastname: Jeong
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001343:Autophagy / Q000528:radiation effects*; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000528:radiation effects; D005260:Female; D006801:Humans; D008027:Light; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D053078:Membrane Potential, Mitochondrial / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism / Q000528:radiation effects*; D009368:Neoplasm Transplantation; D010588:Phagosomes / Q000378:metabolism / Q000528:radiation effects; D010789:Phototherapy / Q000295:instrumentation / Q000379:methods*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000819:agonists / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D013481:Superoxides; C052617:Bcl2 protein, mouse; C025946:3-methyladenine; D011065:Poly(ADP-ribose) Polymerases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D000225:Adenine
keywords: Apoptosis; Autophagy; Light emitting diode; Mitochondrial membrane potential; ROS