Diallyl disulfide attenuated carbon ion irradiation-induced apoptosis in mouse testis through changing the ratio of Tap73/ΔNp73 via mitochondrial pathway.

Abstract

Diallyl disulfide (DADS), a major organosulfur compound derived from garlic, has various biological properties, including anti-cancer effects. However, the protective mechanism of DADS against radiation-induced mouse testis cell apoptosis has not been elucidated. In this study, the magnitude of radiation effects evoked by carbon ion irradiation was marked by morphology changes, significant rise in apoptotic cells, activation expression of p53, up regulation the ratio of pro-apoptotic Tap73/anti-apoptotic ΔNp73, as well as alterations of crucial mediator of the mitochondrial pathway. Interestingly, pretreatment with DADS attenuated carbon ion irradiation-induced morphology damages and apoptotic cells. Additionally, DADS elevated radiation-induced p53 and p21 expression, suggesting that p53 might be involved in the inhibition of cell cycle progression through up regulation of p21. Furthermore, administration with DADS prevented radiation-induced Tap73/ΔNp73 expression and consequently down regulated Bax/Bcl-2 ratio, cytochrome c release and caspase-3 expression, indicating that the balance between Tap73 and ΔNp73 had potential to activate p53 responsive genes. Thus, our results showed that radio protection effect of DADS on mouse testis is mediated by blocking apoptosis through changing the ratio of Tap73/ΔNp73 via mitochondrial pathway, suggesting that DADS could be used as a potential radio protection agent for the testis against heavy-ion radiation.

• Authors: Cui-xia Di, Lu Han, Hong Zhang, Shuai Xu, Ai-hong Mao, Chao Sun, Yang Liu, Jing Si, Hong-yan Li, Xin Zhou, Bing Liu, Guo-ying Miao
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 16020 (Nov 03 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26526304 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Allyl Compounds
• Cyclin-Dependent Kinase Inhibitor p21
• Disulfides
• Ions
• Nuclear Proteins
• Proto-Oncogene Proteins c-bcl-2
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• delta Np73, mouse
• diallyl disulfide
• Cytochromes c
• Caspase 3

Topics

• Allyl Compounds (pharmacology)
• Animals
• Apoptosis (drug effects, radiation effects)
• Caspase 3 (metabolism)
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• Cytochromes c (metabolism)
• Disulfides (pharmacology)
• Down-Regulation (drug effects)
• Garlic (chemistry, metabolism)
• Ions (chemistry)
• Male
• Mice
• Mitochondria (metabolism)
• Nuclear Proteins (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Radiation, Ionizing
• Testis (metabolism, pathology, radiation effects)
• Tumor Suppressor Protein p53 (metabolism)
• Up-Regulation (drug effects)
• Whole-Body Irradiation
• bcl-2-Associated X Protein (metabolism)