scholarly journals Mechanism of thymidine incorporation into acid insoluble fraction via nucleoside transporters on oxidative stress DNA injury

Author(s):  
Koh-ichi Tanaka ◽  
Nobue Kitanaka ◽  
Junichi Kitanaka ◽  
Kazuo Tomita ◽  
Takao Tsukahara ◽  
...  
2011 ◽  
Vol 71 ◽  
pp. e222
Author(s):  
Koh-ichi Tanaka ◽  
Nobue Kitanaka ◽  
Junichi Kitanaka ◽  
Yuriko Kishi ◽  
Shyohn Yokoyama ◽  
...  

Reproduction ◽  
2015 ◽  
Vol 149 (1) ◽  
pp. 113-123 ◽  
Author(s):  
Tania Morielli ◽  
Cristian O'Flaherty

Oxidative stress, generated by excessive reactive oxygen species (ROS) or decreased antioxidant defenses (and possibly both), is associated with male infertility. Oxidative stress results in redox-dependent protein modifications, such as tyrosine nitration andS-glutathionylation. Normozoospermic sperm samples from healthy individuals were included in this study. Samples were incubated with increasing concentrations (0–5 mM) of exogenous hydrogen peroxide, tert-butyl hydroperoxide, or diethylamine NONOate (DA-NONOate, a nitric oxide (NO∙) donor) added to the medium. Spermatozoa treated with or without ROS were incubated under capacitating conditions and then levels of tyrosine phosphorylation and percentage of acrosome reaction (AR) induced by lysophosphatidylcholine were determined. Modified sperm proteins from cytosolic, triton-soluble, and triton-insoluble fractions were analyzed by SDS–PAGE immunoblotting and immunocytochemistry with anti-glutathione and anti-nitrotyrosine antibodies. Levels ofS-glutathionylation increased dose dependently after exposure to hydroperoxides (P<0.05) and were localized mainly to the cytosolic and triton-soluble fractions of the spermatozoa. Levels of tyrosine-nitrated proteins increased dose dependently after exposure to DA-NONOate (P<0.05) and were mainly localized to the triton-insoluble fraction. ROS-treated spermatozoa showed impaired motility without affecting viability (hypo-osmotic swelling test). These treated spermatozoa had tyrosine phosphorylation and AR levels similar to that of non-capacitated spermatozoa following incubation under capacitating conditions, suggesting an impairment of sperm capacitation by oxidative stress. In conclusion, oxidative stress promotes a dose-dependent increase in tyrosine nitration andS-glutathionylation and alters motility and the ability of spermatozoa to undergo capacitation.Free Spanish abstractA Spanish translation of this abstract is freely available athttp://www.reproduction-online.org/content/149/1/113/suppl/DC1.


2015 ◽  
Vol 35 (4) ◽  
pp. 448-453 ◽  
Author(s):  
S Ansar ◽  
M Iqbal

The present study was aimed to study protective effect of butylated hydroxyanisole (BHA), a phenolic antioxidant used in foods on ferric nitrilotriacetate (Fe-NTA)–induced nephrotoxicity. Male albino rats of Wistar strain (4–6 weeks old) weighing 125–150 g were used in this study. Animals were given a single dose of Fe-NTA (9 mg kg−1 body weight) after treatment with BHA (1 and 2 mg animal−1 day−1). Fe-NTA treatment enhanced ornithine decarboxylase (ODC) activity to 5.3-fold, and [3H]-thymidine incorporation in DNA to 2.5-fold in kidney compared with the corresponding saline-treated control, whereas glutathione (GSH) levels and the activities of antioxidant enzymes decreased to a range of 2- to 2.5-fold in kidney. These changes were reversed significantly in animals receiving a pretreatment of BHA. The enhanced ODC activity and DNA synthesis showed a reduction to 2.12-fold and 1.15-fold, respectively, at a higher dose of 2 mg BHA day−1 animal−1, compared with the Fe-NTA-treated groups. Pretreatment with BHA prior to Fe-NTA treatment increased GSH and the activities of antioxidant enzymes to a range of 1.5- to 2-fold in kidney. The results indicate that BHA suppresses Fe-NTA-induced nephrotoxicity in male Wistar rats.


2010 ◽  
Vol 68 ◽  
pp. e126-e127
Author(s):  
Koh-ichi Tanaka ◽  
Nobue Kitanaka ◽  
Junichi Kitanaka ◽  
Tomoaki Sato ◽  
Takashige Nishikawa ◽  
...  

2004 ◽  
Vol 287 (4) ◽  
pp. C1058-C1066 ◽  
Author(s):  
Ho Jae Han ◽  
Min Jin Lim ◽  
Yun Jung Lee

Exposure of renal proximal tubule cells to oxalate may play an important role in cell proliferation, but the signaling pathways involved in this effect have not been elucidated. Thus the present study was performed to examine the effect of oxalate on 3H-labeled thymidine incorporation and its related signal pathway in primary cultured rabbit renal proximal tubule cells (PTCs). The effects of oxalate on [3H]thymidine incorporation, lactate dehydrogenase (LDH) release, Trypan blue exclusion, H2O2 release, activation of mitogen-activated protein kinases (MAPKs), and 3H-labeled arachidonic acid (AA) release were examined in primary cultured renal PTCs. Oxalate inhibited [3H]thymidine incorporation in a time- and dose-dependent manner. However, its analogs did not affect [3H]thymidine incorporation. Oxalate (1 mM) significantly increased H2O2 release, which was blocked by N-acetyl-l-cysteine (NAC) and catalase (antioxidants). Oxalate significantly increased p38 MAPK and stress-activated protein kinase (SAPK)/c-Jun NH2-terminal kinase (JNK) activity, not p44/42 MAPK. Oxalate stimulated [3H]AA release and translocation of cytosolic phospholipase A2 (cPLA2) from the cytosolic fraction to the membrane fraction. Indeed, oxalate significantly increased prostaglandin E2 (PGE2) production compared with control. Oxalate-induced inhibition of [3H]thymidine incorporation and increase of [3H]AA release were prevented by antioxidants (NAC), a p38 MAPK inhibitor (SB-203580), a SAPK/JNK inhibitor (SP-600125), or PLA2 inhibitors [mepacrine and arachidonyl trifluoromethyl ketone (AACOCF3)], but not by a p44/42 MAPK inhibitor (PD-98059). These findings suggest that oxalate inhibits renal PTC proliferation via oxidative stress, p38 MAPK/JNK, and cPLA2 signaling pathways.


2009 ◽  
Vol 65 ◽  
pp. S148
Author(s):  
Koh-ichi Tanaka ◽  
Junichi Kitanaka ◽  
Nobue Kitanaka ◽  
Tomoaki Sato ◽  
Takashige Nishikawa ◽  
...  

1998 ◽  
Vol 17 (3) ◽  
pp. 163-171 ◽  
Author(s):  
Mohammad Iqbal ◽  
Hassan Rezazadeh ◽  
Sabah Ansar ◽  
Mohammad Athar

Ferric nitrilotriacetate (Fe-NTA) is a potent nephrotoxic agent. In this communication, we show the modulatory effect of DL-a-tocopherol (Vitamin-E) on ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative stress, toxicity and hyperproliferative response in rats. Fe-NTA-treatment enhances the susceptibility of renal microsomal membrane for iron-ascorbate-induced lipid peroxidation and hydrogen peroxide generation which are accompanied by a decrease in the activities of renal antioxidant enzymes, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase and depletion in the level of renal glutathione. Parallel to these changes, a sharp increase in blood urea nitrogen and serum creatinine has been observed. In addition, Fe-NTA-treatment also enhances renal ornithine decarboxylase activity (ODC) and increases [3H]thymidine incorporation in renal DNA. Prophylactic treatment of animals with Vit.E daily for 1 week prior to the administration of Fe-NTA resulted in the diminution of Fe-NTA-mediated damage. Enhanced susceptibility of renal microsomal membrane for lipid peroxidation induced by iron-ascorbate and hydrogen peroxide generation were significantly reduced (P50.05). In addition, the depleted level of glutathione and inhibited activities of antioxidant enzymes recovered to significant levels (P50.05). Similarly, the enhanced blood urea nitrogen and serum creatinine levels which are indicative of renal injury showed a reduction of about 50% at a higher dose of Vit.E. The pretreatment of rats with Vit.E reduced the Fe-NTA-mediated induction in ODC activity and enhancement in [3H]thymidine incorporation in DNA. The protective effect of Vit.E was dose dependent. In summary, our data suggest that Vit.E is an effective chemopreventive agent in kidney and may suppress Fe-NTA-induced renal toxicity.


Author(s):  
Koh-ichi Tanaka ◽  
Kento Igarashi ◽  
Kazuo Tomita ◽  
Nobue Kitanaka ◽  
Junichi Kita ◽  
...  

2020 ◽  
Vol 11 (10) ◽  
pp. 8547-8559
Author(s):  
Hongjing Zhao ◽  
Yu Wang ◽  
Mengyao Mu ◽  
Menghao Guo ◽  
Hongxian Yu ◽  
...  

Antibiotics are used worldwide to treat diseases in humans and other animals; most of them and their secondary metabolites are discharged into the aquatic environment, posing a serious threat to human health.


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