Summary and Conclusions

The results summarized in this chapter clearly indicate that polyamines are implicated in regulation of K+ channel activity and intracellular Ca2+ homeostasis in normal intestinal epithelial cells. Polyamines are potent stimulators for expression of the Kv channel genes, and the resultant increase in Kv channel activity is critical for the control of Ca2+ influx by regulating E that governs the driving force for Ca2+ influx during restitution. Increased levels of cellular polyamines activate K+ channel activity,

Fig. 6. Changes in paracellular permeability in IEC-6 cells in the presence or absence of cellular polyamines. After cells were grown in control cultures or cultures containing either 5 mM DFMO alone or DFMO plus 5 |M spermidine (SPD) for 4 d, they were trypsinized, plated at confluent density on the insert, and then maintained at same culture conditions for additional 48 h. The entire basal medium was collected 2 h after addition of [14C]-mannitol or [3H]-inulin for paracellular tracer flux assays. Values are means ± SE of data from eight samples. *p < 0.05 compared with control group; +p < 0.05 compared with DFMO-treated cells.

Fig. 6. Changes in paracellular permeability in IEC-6 cells in the presence or absence of cellular polyamines. After cells were grown in control cultures or cultures containing either 5 mM DFMO alone or DFMO plus 5 |M spermidine (SPD) for 4 d, they were trypsinized, plated at confluent density on the insert, and then maintained at same culture conditions for additional 48 h. The entire basal medium was collected 2 h after addition of [14C]-mannitol or [3H]-inulin for paracellular tracer flux assays. Values are means ± SE of data from eight samples. *p < 0.05 compared with control group; +p < 0.05 compared with DFMO-treated cells.

increase [Ca2+] t through increases in the driving force for Ca2+ influx, and promote cyt cell migration during restitution after injury. In contrast, polyamine depletion decreases epithelial cell migration by reducing [Ca2+]cyt through inactivation of Kv channel activity, thus leading to inhibition of epithelial restitution.

In addition, polyamines are also necessary for expression of intercellular junctions, especially E-cadherin and occludin, in intestinal epithelial cells. Polyamines regulate expression of the E-cadherin gene at transcription level through a process involving Ca2+ and c-Myc transcription factor. Polyamines regulate occludin expression by modulating the synthesis and stability of occludin protein. Increased polyamines enhance expression of intercellular junction proteins and promote function of intestinal epithelial barrier, while depletion of cellular polyamines inhibits expression of various intercellular junction proteins and causes dysfunction of epithelial barrier, thus resulting in an increase in paracellular permeability.

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