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OP0065 Abnormalities in the pkc signalling system downstream to muscarinic receptors in an experimental model for sjÖgren’s syndrome (ss)
  1. YT Konttinen,
  2. EK Tensing,
  3. M Hukkanen,
  4. HS Fox,
  5. J Ma,
  6. J Tornwall
  1. Department of Oral Medicine, Surgical Hospital, Helsinki, Finland

Abstract

Background Postganglionic parasympathetic nerve fibers1 release acetylcholine, which binds to acinar cell muscarinic receptors. Short-term stimulation leads to activation, but long-term stimulation leads to a negative feedback in form of proteolytic degradation. Salivary glands acinar cells in SS patients lack PKC beta II and are low in PKC alpha isoform2 as if they had been consumed/proteolytically degraded.

Objectives Our aim was to study, if also NOD mice have PKC involvement, which isoforms are involved and if this involvement is of the early activation type or like is seen as a result of a long-term, autoantibody-mediated stimulation in human disease.

Methods Conventinal (alpha, beta, gamma), unusual (delta, epsilon, theta) and atypical (lambda, iota) PKC isoforms were studied using immunohistochemical staining and Western blotting.

Results Control BALB/c mice had PKC alpha and beta like their human counterparts. They require calcium, DAG and phosphatidylserine for their activation. In contrast, NOD mice with sialadenitis had a strong expression of PKC alpha and beta. Transgenic NOD x IFN-gamma mice had an early involvement, but similar pattern to that of NOD mice. Acinar cells in NOD scid mice did not express any of the PKC isoforms studied.

Conclusion Findings suggest that the calcium-dependent conventional PKC isoforms are involved also in NOD mice. In contrast to the human disease, mice with a short life span display upregulation and do not reach the stage with proteolytic degradation/loss of PKC. Interestingly, the altered PKC status modulates the susceptibility of cells to apoptosis.

References

  1. Konttinen YT, Hukkanen M, Kemppinen P, et al. Arthritis Rheum. 1992;35:815–20

  2. Törnwall J, Konttinen YT, Tuominen RK, Törnwall M. Lancet 1997;349:1814–15

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