Ne. Zorn et al., ALTERATIONS IN SPLENOCYTE PROTEIN-KINASE-C (PKC) ACTIVITY BY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN IN-VIVO, Toxicology letters, 78(2), 1995, pp. 93-100
The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on growth fa
ctor-coupled activation of nuclear protein kinase C (nPKC) and on the
subcellular distribution of PKC activity in rat splenocytes were inves
tigated. Seven days after a single injection of TCDD (50 mu g/kg body
weight), cytosolic and particulate PKC activity was significantly high
er in splenocytes from TCDD-treated rats or pair-fed control rats comp
ared to ad libitum-fed animals. In a separate experiment, purified spl
enocyte nuclei from TCDD-treated animals and controls were used to stu
dy activation of nPKC by growth factors and other trophic agents. Grow
th factor-stimulated nPKC activation was attenuated in splenic nuclei
from TCDD-treated rats compared to vehicle-treated controls. Evidence
presented here suggests that the cellular mechanism of TCDD toxicity l
eading to immunosuppression in rodents may be mediated in part by unco
upling of growth factor receptors linked to PKC activation at the leve
l of the nucleus. However, changes in total splenocyte PKC activity ap
pear to be correlated with hypophagia since cytosolic and particulate
PKC levels were elevated in TCDD-treated rats and their pair-fed partn
ers.