NFkappaB and caspase-3 activity in apoptotic hepatocytes of galactosamine-sensitized mice treated with TNFalpha.
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NFkappaB and caspase-3 activity in apoptotic hepatocytes of galactosamine-sensitized mice treated with TNFalpha. / Tapalaga, Dan; Tiegs, Gisa; Angermüller, Sabine.
In: J HISTOCHEM CYTOCHEM, Vol. 50, No. 12, 12, 2002, p. 1599-1609.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - NFkappaB and caspase-3 activity in apoptotic hepatocytes of galactosamine-sensitized mice treated with TNFalpha.
AU - Tapalaga, Dan
AU - Tiegs, Gisa
AU - Angermüller, Sabine
PY - 2002
Y1 - 2002
N2 - Tumor necrosis factor-alpha (TNFalpha) induces apoptosis in hepatocytes only under transcriptional arrest induced by galactosamine (GalN). In this study we demonstrated the shuttle of the transcription factor NFkappaB (nuclear factor-kappa B) in the liver tissue of mice within 30 min-4.5 hr hours after GalN/TNFalpha treatment. NFkappaB translocation from cytoplasm to the nucleus is initiated by its separation from the inhibitory IkappaB proteins which include IkappaBalpha, IkappaBbeta, and IkappaB. Thirty minutes after GalN/TNFalpha administration, NFkappaBp65 in hepatocellular nuclei becomes increasingly detectable and reaches its highest level after 2.5 hr. Then export back into cytoplasm begins but, surprisingly, approximately 30% of NFkappaB remains in the nuclear fraction and appears as an immunoprecipitate in the nuclei of apoptotic hepatocytes. Non-apoptotic hepatocytes do not show any reaction product in the nuclei 4.5 hr after treatment. Correspondingly, the amount of dissociated IkappaBbeta decreases in the cytoplasm up to 2.5 hr and increases again afterwards, although it does not reach the level of the control samples. No evidence of IkappaBbeta in the nuclei was found either immunocytochemically or biochemically. Caspase-3 activity, which is responsible for apoptosis, increases significantly after 3.5 hr. At that time, apoptotic hepatocytes can occasionally be observed and, 4.5 hr after GalN/TNFalpha treatment, constitute approximately 30% of the hepatocytes.
AB - Tumor necrosis factor-alpha (TNFalpha) induces apoptosis in hepatocytes only under transcriptional arrest induced by galactosamine (GalN). In this study we demonstrated the shuttle of the transcription factor NFkappaB (nuclear factor-kappa B) in the liver tissue of mice within 30 min-4.5 hr hours after GalN/TNFalpha treatment. NFkappaB translocation from cytoplasm to the nucleus is initiated by its separation from the inhibitory IkappaB proteins which include IkappaBalpha, IkappaBbeta, and IkappaB. Thirty minutes after GalN/TNFalpha administration, NFkappaBp65 in hepatocellular nuclei becomes increasingly detectable and reaches its highest level after 2.5 hr. Then export back into cytoplasm begins but, surprisingly, approximately 30% of NFkappaB remains in the nuclear fraction and appears as an immunoprecipitate in the nuclei of apoptotic hepatocytes. Non-apoptotic hepatocytes do not show any reaction product in the nuclei 4.5 hr after treatment. Correspondingly, the amount of dissociated IkappaBbeta decreases in the cytoplasm up to 2.5 hr and increases again afterwards, although it does not reach the level of the control samples. No evidence of IkappaBbeta in the nuclei was found either immunocytochemically or biochemically. Caspase-3 activity, which is responsible for apoptosis, increases significantly after 3.5 hr. At that time, apoptotic hepatocytes can occasionally be observed and, 4.5 hr after GalN/TNFalpha treatment, constitute approximately 30% of the hepatocytes.
KW - Animals
KW - Male
KW - Immunohistochemistry
KW - Mice
KW - Mice, Inbred BALB C
KW - Blotting, Western
KW - In Situ Nick-End Labeling
KW - Apoptosis
KW - Cell Nucleus/metabolism
KW - NF-kappa B/metabolism
KW - Caspase 3
KW - Caspases/metabolism
KW - Galactosamine/pharmacology
KW - Hepatocytes/cytology/metabolism/ultrastructure
KW - Plastic Embedding
KW - Tumor Necrosis Factor-alpha/pharmacology/physiology
KW - Animals
KW - Male
KW - Immunohistochemistry
KW - Mice
KW - Mice, Inbred BALB C
KW - Blotting, Western
KW - In Situ Nick-End Labeling
KW - Apoptosis
KW - Cell Nucleus/metabolism
KW - NF-kappa B/metabolism
KW - Caspase 3
KW - Caspases/metabolism
KW - Galactosamine/pharmacology
KW - Hepatocytes/cytology/metabolism/ultrastructure
KW - Plastic Embedding
KW - Tumor Necrosis Factor-alpha/pharmacology/physiology
M3 - SCORING: Journal article
VL - 50
SP - 1599
EP - 1609
JO - J HISTOCHEM CYTOCHEM
JF - J HISTOCHEM CYTOCHEM
SN - 0022-1554
IS - 12
M1 - 12
ER -
