Rapamycin inhibits acrolein-induced apoptosis by alleviating ROS-driven mitochondrial dysfunction in male germ cells.
OBJECTIVE
Acrolein (Acr) is a highly reactive α, β-unsaturated aldehyde, which can induce reactive oxygen species (ROS) generation. Several factors, including lipid peroxidation, clinical use of cyclophosphamide, fried foods, automobile exhausts, smoking and aging can increase its concentration in blood serum. Mounting evidence has suggested that Acr-induced ROS might reduce quality of sperm. Thus, the aim of this study was to examine reproductive toxicity of Acr-caused ROS in vitro and find a means to alleviate it.


METHODS
We investigated the effects of Acr on male germ cell (MGC)-derived GC-1 cells in vitro. Dihydroethidium and DCFH-DA fluorescent dyes were used to determine generation of intracellular ROS.


RESULTS
We found that Acr induced ROS generation, which was accompanied by reduced Bcl2/Bax ratio, substantial decline in mitochondrial membrane potential, and further promoted apoptosis of MGCs. Furthermore, Rapamycin was capable of alleviating Acr-induced ROS, reducing ROS-induced apoptosis by increasing ratio of Bcl2/Bax mRNA and proteins, and protecting MGC mitochondrial membranes.


CONCLUSIONS
Rapamycin inhibited Acr-induced apoptosis by alleviating ROS-driven mitochondrial dysfunction in MGCs.
College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Key Lab for Animal Biotechnology of Agriculture Ministry of China, Northwest A&F University, Yangling, 712100, Shaanxi, China.
X
X
He
W
W
Song
C
C
Liu
S
S
Chen
J
J
Hua
D000171:Acrolein / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D013090:Spermatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013091:Spermatogenesis / Q000187:drug effects; D013093:Spermatogonia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
C494827:Bax protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C052617:Bcl2 protein, mouse; D000171:Acrolein; D005978:Glutathione; D020123:Sirolimus