[Mitochondria-targeted antioxidant SkQR1 selectively protects MDR-negative cells against ionizing radiation].
Radioprotection appeared to be an important problem of today due to atom energetic development and utilization of radiation material in the industry, science and medicine. It has been shown that mitochondrial targeted antioxidant SkQR1 could attenuate radiation injury of human erythroleukemia K562 cells. Pretreatment with SkQR1 before irradiation decreased DNA double strand breaks formation, diminished the number of chromosomal aberrations and suppressed delayed ROS production. Prevention of oxidative stress and normalization of mitochondrial function by mitochondria-targeted antioxidants may be a potential therapeutic strategy not only against immediate consequences of radiation, but, either against its late consequences such as genomic instability. SkQR1 did not protect against radiation-induced damage the K562 subline with high level of multidrug resistance (MDR) due to SkQR1 extrusion with Pgp 170 MDR pump. We suggest that mitochondria-targeted antioxidants might be used for selective protection of normal cells against radiation-induced damage without interference with radiotherapy of MDR-positive tumors.
E K
EK
Fetisova
M M
MM
Antoshina
V D
VD
Cherepanynets
D S
DS
Izumov
I I
II
Kireev
R I
RI
Kireev
K G
KG
Lyamzaev
N I
NI
Riabchenko
B V
BV
Chernyak
V P
VP
Skulachev
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D001692:Biological Transport; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002869:Chromosome Aberrations / Q000187:drug effects* / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005720:Gamma Rays; D015870:Gene Expression; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D009928:Organ Specificity; D010971:Plastoquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012235:Rhodamines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
C534903:10-(6'-plastoquinonyl) decylrhodamine 19; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000975:Antioxidants; C468783:H2AX protein, human; D006657:Histones; D017382:Reactive Oxygen Species; D012235:Rhodamines; D010971:Plastoquinone