Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
116-208 |
DRI_Approach |
denotes |
Protein kinase C (PKC) activation and increases in cytosolic Ca(2+) cause intestinal injury. |
T2 |
209-412 |
DRI_Outcome |
denotes |
Since PKC activation can alter Ca(2+) homeostasis and increase Ca(2+) levels, we examined the effects of PKC activation on intestinal cellular integrity and the role of Ca(2+) signaling in this response. |
T3 |
413-514 |
DRI_Background |
denotes |
The epithelial cell line, IEC-18 was incubated with the PKC activator phorbol myristate acetate (PMA; |
T4 |
529-531 |
DRI_Background |
denotes |
). |
T5 |
532-596 |
DRI_Background |
denotes |
In some experiments, cells were incubated in Ca(2+)-free medium. |
T6 |
597-687 |
DRI_Background |
denotes |
PMA treatment produced a concentration-dependent increase in cell injury and PKC activity. |
T7 |
688-775 |
DRI_Approach |
denotes |
This response was attenuated by addition of the pan-specific PKC inhibitor, GF 109203X. |
T8 |
776-915 |
DRI_Background |
denotes |
Furthermore, cell viability was maintained in cells preincubated with PKC isoform-specific inhibitors to PKCalpha, PKCdelta and PKCepsilon. |
T9 |
916-1074 |
DRI_Approach |
denotes |
Cell injury was also reduced if cells were incubated in Ca(2+)-free medium or in the presence of the Ca(2+) channel antagonist, verapamil or the intracellular |
T10 |
1092-1093 |
DRI_Approach |
denotes |
. |
T11 |
1094-1318 |
DRI_Approach |
denotes |
PMA, but not the inactive phorbol ester, 4alphaPMA, induced a dose-dependent increase in cellular Ca(2+) that was characterized by a rapid, transient spike followed by a tonic plateau phase which approximated control levels. |
T12 |
1319-1379 |
DRI_Approach |
denotes |
These responses were eliminated by the addition of BAPTA-AM. |
T13 |
1380-1508 |
DRI_Outcome |
denotes |
Furthermore the increase in the Ca(2+) spike was reduced or eliminated by co-incubation with the PKCdelta antagonist, rottlerin. |
T14 |
1509-1595 |
DRI_Background |
denotes |
Inhibition of PKCalpha or PKCepsilon was less effective or ineffective in this regard. |
T15 |
1596-1710 |
DRI_Outcome |
denotes |
These data suggest that PKC activation via PMA challenge affects the integrity of rat intestinal epithelial cells. |
T16 |
1711-1829 |
DRI_Background |
denotes |
PKCdelta, but not PKCepsilon or PKCalpha activation appears to mediate this effect via an increase in cellular Ca(2+). |