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Gastroenterology. 2002 Feb;122(2):483-94.

Selective modulation of PKC isozymes by inflammation in canine colonic circular muscle cells.

Author information

  • 1Department of Surgery, Medical College of Wisconsin, and Zablocki Veteran Affairs Medical Center, Milwaukee, Wisconsin, USA.

Abstract

BACKGROUND & AIMS:

Protein kinase C (PKC) is a key signaling molecule in excitation-contraction coupling in several types of smooth muscle cells. We investigated whether the attenuated contraction in inflamed colon cells is caused by alterations in the expression, distribution, and activation of specific PKC isozymes.

METHODS:

Kinase assays, immunofluorescence imaging, and Western immunoblotting were performed on single circular smooth muscle cells obtained from the normal dog colon as well as from colon with experimental colitis induced by mucosal exposure to ethanol and acetic acid, to determine the distribution, expression, and activation of PKC isozymes.

RESULTS:

Classical (alpha, beta, and gamma), novel (delta and epsilon), and the atypical PKC (iota, lambda, and zeta) isozymes were detected in colonic circular muscle cells. The expression of PKC alpha, beta, and epsilon isozymes was down-regulated, whereas that of PKC iota and lambda isozymes was up-regulated; other isozymes were not affected by inflammation. Acetylcholine (ACh) treatment translocated only the PKC alpha, beta, and epsilon isozymes from the cytosol to the membrane in normal cells; this translocation was absent in inflamed colon cells. Immunofluorescence imaging confirmed the translocation of PKC alpha from the cytosol to the membrane in response to ACh in normal cells. PKC inhibitors, chelerythrine, and myristoylated peptides to alpha, beta, and epsilon isozymes inhibited the contractile response to ACh in normal, but not in inflamed, cells. PKC iota and lambda did not participate in the contractile response to ACh.

CONCLUSIONS:

ACh-induced contraction is mediated by PKC alpha, beta, and epsilon isozymes in normal colonic circular muscle cells. Contractile dysfunction in inflamed colon cells is, in part, caused by decreased expression and impaired activation of specific PKC isozymes.

PMID:
11832462
[PubMed - indexed for MEDLINE]
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