Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Disease
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Animals
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Apoptosis / drug effects
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Caspase 3 / biosynthesis
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Caspase 3 / genetics
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Chaperonin 60 / biosynthesis
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Chaperonin 60 / genetics
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Chaperonin 60 / physiology*
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Cytochromes c / metabolism
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Endotoxemia / chemically induced
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Endotoxemia / physiopathology*
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Endotoxins / toxicity*
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HMGB1 Protein / biosynthesis
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HMGB1 Protein / genetics
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HMGB1 Protein / physiology*
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HMGB2 Protein / biosynthesis
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HMGB2 Protein / genetics
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HMGB2 Protein / physiology*
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Leydig Cells / drug effects*
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Leydig Cells / metabolism
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Male
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Mitochondria / physiology*
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Orchitis / chemically induced*
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Orchitis / physiopathology
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerases / biosynthesis
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Poly(ADP-ribose) Polymerases / genetics
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Poly(ADP-ribose) Polymerases / physiology
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Rats
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Rats, Wistar
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Spermatogenesis / drug effects*
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Spermatogenesis / physiology
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bcl-2-Associated X Protein / biosynthesis
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bcl-2-Associated X Protein / genetics
Substances
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Bax protein, rat
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Chaperonin 60
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Endotoxins
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HMGB1 Protein
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HMGB2 Protein
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Hbp1 protein, rat
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Proto-Oncogene Proteins c-bcl-2
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bcl-2-Associated X Protein
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endotoxin, Escherichia coli
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Cytochromes c
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Parp1 protein, rat
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerases
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Casp3 protein, rat
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Caspase 3