Bacterial LPS-mediated acute inflammation-induced spermatogenic failure in rats: role of stress response proteins and mitochondrial dysfunction.
Bacterial Lipopolysaccharide (LPS) induced inflammation is implicated in the infection associated testicular tissue damage. Earlier, using a LPS induced acute endotoxemic rat model, we have shown the involvement of inflammation-induced oxidative stress in the impaired steroidogenesis and spermatogenesis. In the present study, we report a significant induction (more than 2-fold) of stress response proteins HSP-60, HMGB-1 and 2 in the testes, as early as 6 h after LPS injection with a later decrease. This induction of acute stress is closely followed by a significant reduction (74%) in Bcl2/Bax ratio along with leakage of cytochrome c (3 fold increase, p < 0.05) from mitochondria and increased caspase-3 activity levels (2.9 fold, p < 0.05) at 12 h and 24 h post LPS injection respectively. Further studies on PARP cleavage revealed a pattern similar to necrotic death during early periods (3 h to 24 h) and apoptosis at later periods (24 h to 72 h) after LPS treatment. In conclusion, the present study shows the involvement of stress response proteins and mitochondrial dysfunction in LPS-induced germ cell death in male rats.
Metukuri
Mallikarjuna Reddy
MR
Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad, AP, India.
Reddy
Chandra Mohan T
CM
Reddy
P R K
PR
Reddanna
Pallu
P
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics; D018834:Chaperonin 60 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D045304:Cytochromes c / Q000378:metabolism; D019446:Endotoxemia / Q000139:chemically induced / Q000503:physiopathology*; D004731:Endotoxins / Q000633:toxicity*; D024243:HMGB1 Protein / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D024261:HMGB2 Protein / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000502:physiology*; D009920:Orchitis / Q000139:chemically induced* / Q000503:physiopathology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013091:Spermatogenesis / Q000187:drug effects* / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
C494828:Bax protein, rat; D018834:Chaperonin 60; D004731:Endotoxins; D024243:HMGB1 Protein; D024261:HMGB2 Protein; C104200:Hbp1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C044101:endotoxin, Escherichia coli; D045304:Cytochromes c; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C505410:Casp3 protein, rat; D053148:Caspase 3