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Oxidative stress and its significant roles in neurodegenerative diseases and cancer.

Thanan R, Oikawa S, Hiraku Y, Ohnishi S, Ma N, Pinlaor S, Yongvanit P, Kawanishi S, Murata M - Int J Mol Sci (2014)

Bottom Line: Accumulating evidence indicates that oxidative damage to biomolecules including lipids, proteins and DNA, contributes to these diseases.Our recent studies identifying and characterizing carbonylated proteins reveal oxidative damage to heat shock proteins in neurodegenerative disease models and inflammation-related cancer, suggesting dysfunction in their antioxidative properties.Immunohistochemical analyses showed co-localization of oxidative/nitrative DNA lesions and stemness markers in the cells of inflammation-related cancers.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. mrsomchaip@yahoo.com.

ABSTRACT
Reactive oxygen and nitrogen species have been implicated in diverse pathophysiological conditions, including inflammation, neurodegenerative diseases and cancer. Accumulating evidence indicates that oxidative damage to biomolecules including lipids, proteins and DNA, contributes to these diseases. Previous studies suggest roles of lipid peroxidation and oxysterols in the development of neurodegenerative diseases and inflammation-related cancer. Our recent studies identifying and characterizing carbonylated proteins reveal oxidative damage to heat shock proteins in neurodegenerative disease models and inflammation-related cancer, suggesting dysfunction in their antioxidative properties. In neurodegenerative diseases, DNA damage may not only play a role in the induction of apoptosis, but also may inhibit cellular division via telomere shortening. Immunohistochemical analyses showed co-localization of oxidative/nitrative DNA lesions and stemness markers in the cells of inflammation-related cancers. Here, we review oxidative stress and its significant roles in neurodegenerative diseases and cancer.

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Related in: MedlinePlus

Double-immunofluorescence staining of stem/progenitor cell markers (CD133, Oct3/4, OV6 and CD44) and DNA lesions (8-oxodG and 8-nitroguanine (8-NG)) in cholangiocarcinoma tissues. White arrows indicate co-localization of DNA damage marker and stemness marker in cancer cells. Original magnification is ×400; Scale bar = 25 μm.
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ijms-16-00193-f004: Double-immunofluorescence staining of stem/progenitor cell markers (CD133, Oct3/4, OV6 and CD44) and DNA lesions (8-oxodG and 8-nitroguanine (8-NG)) in cholangiocarcinoma tissues. White arrows indicate co-localization of DNA damage marker and stemness marker in cancer cells. Original magnification is ×400; Scale bar = 25 μm.

Mentions: It has been suggested that stem/progenitor cells play roles in inflammation-related carcinogenesis [117,118]. Cells that have the ability to perpetuate themselves through self-renewal and to generate mature cells of a particular tissue by differentiation are defined as stem cells. Several mutations occur in cancer cells suggesting that cancer is a disease of genes, in which a cell ignores growth-limiting signals and forms a tumor that eventually leads to the death of the organism [119]. Not all tumor cells can participate in tumor evolution, and instead, this property is limited to a subset of cells, termed “cancer stem cells (CSCs)” which are also believed to be tumor initiating cells and resistant to oxidative stress, radiotherapy and chemotherapy [119,120]. Many proteins have been proposed as stemness markers in various types of cancers [121]. CD133, Oct3/4, CD44 and oval marker 6 (OV6) were proposed to be stemness markers in liver fluke-related cholangiocarcinoma [107]. Oct3/4 and CD44v6 were also used as stemness markers in bladder cancers [98,122]. Oct3/4 and CD44 expressions were reported to play important roles in the induction of antioxidant defense systems through thioredoxin and glutathione [123,124,125]. Moreover, several lines of evidence also suggested that CSCs have lower intracellular ROS contents and more resistance to oxidative stress and radiotherapy than non-CSCs, which may be due to the increased expression of antioxidant systems [126]. However, our recent publications demonstrated that DNA lesions (8-oxodG and 8-nitroguanine) were formed in CSCs that had Oct3/4 expression in S. haematobium-associated bladder cancer, and CD133, Oct3/4, oval marker 6 (OV6) and CD44 expressions in O. viverrini-associated cholangiocarcinoma [121]. Additionally, DNA lesions were significantly increased in O. viverrini-associated cholangiocarcinoma patients with high expressions of CD133 and/or Oct3/4 in their tumor tissues, whereas there were no significant differences of DNA lesions, in patients, between CD44 and/or OV6-positive and negative tumor tissues [101]. Interestingly, Oct3/4 was highly expressed in S. heamatobium-associated bladder cancers and was significantly related with high DNA damage formation whereas CD44v6 was related with low DNA damage formation in bladder cancers without the parasite infection [98,122]. Figure 4 shows the co-localization of stemness markers including CD133, Oct3/4, oval marker 6 (OV6) and CD44 with DNA lesions in clinical cholangiocarcinoma tissues. These studies strongly indicated that in some cases the redox status of the stem cells fails to protect the cells from oxidative damage which contributes to DNA damage, mutation and genetic instability of the CSCs resulting in tumor progression with a poor prognostic outcome.


Oxidative stress and its significant roles in neurodegenerative diseases and cancer.

Thanan R, Oikawa S, Hiraku Y, Ohnishi S, Ma N, Pinlaor S, Yongvanit P, Kawanishi S, Murata M - Int J Mol Sci (2014)

Double-immunofluorescence staining of stem/progenitor cell markers (CD133, Oct3/4, OV6 and CD44) and DNA lesions (8-oxodG and 8-nitroguanine (8-NG)) in cholangiocarcinoma tissues. White arrows indicate co-localization of DNA damage marker and stemness marker in cancer cells. Original magnification is ×400; Scale bar = 25 μm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307243&req=5

ijms-16-00193-f004: Double-immunofluorescence staining of stem/progenitor cell markers (CD133, Oct3/4, OV6 and CD44) and DNA lesions (8-oxodG and 8-nitroguanine (8-NG)) in cholangiocarcinoma tissues. White arrows indicate co-localization of DNA damage marker and stemness marker in cancer cells. Original magnification is ×400; Scale bar = 25 μm.
Mentions: It has been suggested that stem/progenitor cells play roles in inflammation-related carcinogenesis [117,118]. Cells that have the ability to perpetuate themselves through self-renewal and to generate mature cells of a particular tissue by differentiation are defined as stem cells. Several mutations occur in cancer cells suggesting that cancer is a disease of genes, in which a cell ignores growth-limiting signals and forms a tumor that eventually leads to the death of the organism [119]. Not all tumor cells can participate in tumor evolution, and instead, this property is limited to a subset of cells, termed “cancer stem cells (CSCs)” which are also believed to be tumor initiating cells and resistant to oxidative stress, radiotherapy and chemotherapy [119,120]. Many proteins have been proposed as stemness markers in various types of cancers [121]. CD133, Oct3/4, CD44 and oval marker 6 (OV6) were proposed to be stemness markers in liver fluke-related cholangiocarcinoma [107]. Oct3/4 and CD44v6 were also used as stemness markers in bladder cancers [98,122]. Oct3/4 and CD44 expressions were reported to play important roles in the induction of antioxidant defense systems through thioredoxin and glutathione [123,124,125]. Moreover, several lines of evidence also suggested that CSCs have lower intracellular ROS contents and more resistance to oxidative stress and radiotherapy than non-CSCs, which may be due to the increased expression of antioxidant systems [126]. However, our recent publications demonstrated that DNA lesions (8-oxodG and 8-nitroguanine) were formed in CSCs that had Oct3/4 expression in S. haematobium-associated bladder cancer, and CD133, Oct3/4, oval marker 6 (OV6) and CD44 expressions in O. viverrini-associated cholangiocarcinoma [121]. Additionally, DNA lesions were significantly increased in O. viverrini-associated cholangiocarcinoma patients with high expressions of CD133 and/or Oct3/4 in their tumor tissues, whereas there were no significant differences of DNA lesions, in patients, between CD44 and/or OV6-positive and negative tumor tissues [101]. Interestingly, Oct3/4 was highly expressed in S. heamatobium-associated bladder cancers and was significantly related with high DNA damage formation whereas CD44v6 was related with low DNA damage formation in bladder cancers without the parasite infection [98,122]. Figure 4 shows the co-localization of stemness markers including CD133, Oct3/4, oval marker 6 (OV6) and CD44 with DNA lesions in clinical cholangiocarcinoma tissues. These studies strongly indicated that in some cases the redox status of the stem cells fails to protect the cells from oxidative damage which contributes to DNA damage, mutation and genetic instability of the CSCs resulting in tumor progression with a poor prognostic outcome.

Bottom Line: Accumulating evidence indicates that oxidative damage to biomolecules including lipids, proteins and DNA, contributes to these diseases.Our recent studies identifying and characterizing carbonylated proteins reveal oxidative damage to heat shock proteins in neurodegenerative disease models and inflammation-related cancer, suggesting dysfunction in their antioxidative properties.Immunohistochemical analyses showed co-localization of oxidative/nitrative DNA lesions and stemness markers in the cells of inflammation-related cancers.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. mrsomchaip@yahoo.com.

ABSTRACT
Reactive oxygen and nitrogen species have been implicated in diverse pathophysiological conditions, including inflammation, neurodegenerative diseases and cancer. Accumulating evidence indicates that oxidative damage to biomolecules including lipids, proteins and DNA, contributes to these diseases. Previous studies suggest roles of lipid peroxidation and oxysterols in the development of neurodegenerative diseases and inflammation-related cancer. Our recent studies identifying and characterizing carbonylated proteins reveal oxidative damage to heat shock proteins in neurodegenerative disease models and inflammation-related cancer, suggesting dysfunction in their antioxidative properties. In neurodegenerative diseases, DNA damage may not only play a role in the induction of apoptosis, but also may inhibit cellular division via telomere shortening. Immunohistochemical analyses showed co-localization of oxidative/nitrative DNA lesions and stemness markers in the cells of inflammation-related cancers. Here, we review oxidative stress and its significant roles in neurodegenerative diseases and cancer.

Show MeSH
Related in: MedlinePlus