Selenium variation induced oxidative stress regulates p53 dependent germ cell apoptosis: plausible involvement of HSP70-2.
BACKGROUND
Selenium at altered concentration causes abnormal spermatogenesis and male infertility. However, the exact mechanism behind this is still unexplored.


OBJECTIVE
It was aimed to investigate if Se induced oxidative stress alters the expressions of testis specific HSP70-2 protein, that is crucial in normal spermatogenesis. The study was extended to delineate the apoptotic process after this change if any.


METHODS
To create different Se status-deficient, adequate and excess, male Balb/c mice were fed yeast based Se deficient diet (group I) and this diet supplemented with Se as sodium selenite at 0.2 and 1 ppm Se (group II and III, respectively) for 8 weeks.


RESULTS
After the feeding schedule, a dose dependent change in the Se levels and GSH-Px activity was observed in samples of different Se diet fed group animals as reported in earlier studies. Changes in the redox status in both groups I and III indicated oxidative stress conditions. The mRNA and protein expression of HSP70-2 was found to be reduced in group I and III, whereas, the expressions of p53 demonstrated a reverse trend. Increased apoptosis was observed in the group I and III animals as indicated by increased apoptotic index (AI) on the TUNEL stained sections and by DNA fragmentation indicating DNA damage in these groups.


CONCLUSIONS
These findings suggest that Se variations induced oxidative stress leads to germ cell apoptosis and downregulation of HSP70-2. This study suggests that there can be a possible link between these two events and the fate of HSP70-2 in case of oxidative damage can provide an insight into the mechanism(s) by which the nutritional variation induced oxidative stress can affect reproductive potential and thus demonstrates the importance of nutrition at molecular level as well.
Kaushal
Naveen
N
Department of Biophysics, Panjab University, Chandigarh, 160014, India.
Bansal
M P
MP
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D004249:DNA Damage; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005979:Glutathione Peroxidase / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007248:Infertility, Male / Q000209:etiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012643:Selenium / Q000172:deficiency / Q000494:pharmacology*; D013091:Spermatogenesis / Q000187:drug effects* / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000975:Antioxidants; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D005979:Glutathione Peroxidase; D012643:Selenium