Metallothionein-III prevents gamma-ray-induced 8-oxoguanine accumulation in normal and hOGG1-depleted cells.
Metallothioneins (MT) play an important biological role in preventing oxidative damage to cells. We have previously demonstrated that the efficiency of the protective effect of MT-III against the DNA degradation from oxidative damage was much higher than that of MT-I/II. As an extension of the latter investigation, this study aimed to assess the ability of MT-III to suppress 8-oxoguanine (8-oxoG), which is one of the major base lesions formed after an oxidative attack to DNA and the mutant frequency of the HPRT gene in human fibroblast GM00637 cells upon exposure to gamma-rays. We found that human MT-III expression decreased the level of 8-oxoG and mutation frequency in the gamma-irradiated cells. Using an 8-oxoguanine DNA glycosylase (OGG1)-specific siRNAs, we also found that MT-III expression resulted in the suppression of the gamma-radiation-induced 8-oxoG accumulation and mutation in the OGG1-depleted cells. Moreover, the down-regulation of MT in human neuroblastoma SKNSH cells induced by MT-specific siRNA led to a significant increase in the 8-oxoG level, after exposure to gamma-irradiation. These results suggest that under the conditions of gamma-ray oxidative stress, MT-III prevents the gamma-radiation-induced 8-oxoG accumulation and mutation in normal and hOGG1-depleted cells, and this suppression might, at least in part, contribute to the anticarcinogenic and neuroprotective role of MT-III.
Jeong
Hye Gwang
HG
Research Center for Proteineous Materials, Chosun University, 375 Seosuk-dong, Gwangju 501-759, Korea.
Youn
Cha-Kyung
CK
Cho
Hyun-Ju
HJ
Kim
Soo-Hyun
SH
Kim
Mi-Hwa
MH
Kim
Hong-Beum
HB
Chang
In-Youb
IY
Lee
Yun-Sil
YS
Chung
Myung-Hee
MH
You
Ho Jin
HJ
D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism*; D004252:DNA Mutational Analysis; D043382:DNA-Formamidopyrimidine Glycosylase / Q000737:chemistry; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism; D005720:Gamma Rays; D020868:Gene Silencing; D005822:Genetic Vectors; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D000090023:Metallothionein 3; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000975:Antioxidants; D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; D007770:L-Lactate Dehydrogenase; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D043382:DNA-Formamidopyrimidine Glycosylase