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			PubMed Journals: J Biol Chem

  Source:		PMID: 11713246


    		J Biol Chem. 2002 Jan 18;277(3):1974-80.
     		Epub 2001 Nov 16.

			Transforming growth factor-beta 1 regulates
			Kir2.3 inward rectifier K+ channels via
			phospholipase C and protein kinase C-delta
			in reactive astrocytes from adult rat brain.

			Perillan PR(1), Chen M, Potts EA, Simard
			JM.

			Author Information
			(1) Department of Neurosurgery,
			University of Maryland School of Medicine,
			Baltimore, Maryland 21201, USA.

			The multifunctional cytokine, transforming
			growth factor beta(1) (TGF-beta(1)), exerts
			complex effects on astrocytes with early
			signaling events being less well characterized
			than transcriptional mechanisms. We examined
			the effect of TGF-beta(1) on the 14-pS Kir2.3
			inward rectifier K(+) channel in rat primary
			cultured reactive astrocytes. Immunofluorescence
			study showed that cells co-expressed TGF-beta(1)
			receptors 1 and 2, Kir2.3, and
			glial fibrillary acidic protein (GFAP).
			Patch clamp study showed that TGF-beta(1)
			(0.1-100 ng/ml) caused a rapid (<5 min)
			depolarization because of dose-dependent
			down-regulation of Kir2.3 channels, which
			was mimicked by the protein kinase C (PKC)
			activator phorbol 12-myristate 13-acetate
			(10-500 nm) and which was inhibited by the
			PKC inhibitor calphostin C (100 nm), by
			PKC desensitization produced by 3 h of exposure
			to phorbol 12-myristate 13-acetate (100
			nm), and by the PKC-delta isoform-specific
			inhibitor rottlerin (50 microm). Immunoblot
			analysis and confocal imaging showed that
			TGF-beta(1) caused PKC-delta translocation
			to membrane, and co-immunoprecipitation
			experiments showed that TGF-beta(1) enhanced
			association between Kir2.3 and PKC-delta.
			Additional electrophysiological experiments showed that
			Kir2.3 channel down-regulation was blocked
			by the phospholipase C inhibitors, neomycin
			(100 microm) and D609 (200 microm). Given
			the commonality of signaling involving
			PLC-PKC-delta, we speculate that TGF-beta(1)-evoked
			depolarization may be an early signaling
			event related to gene transcription in astrocytes.

			DOI: 10.1074/jbc.M107984200 PMID: 11713246
			[Indexed for MEDLINE]

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