Cyclic stretch decreases TRPC4 protein and capacitative calcium entry in rat vascular smooth muscle cells

We investigated whether cyclic stretch affects TRPC4 or TRPC6 expression and calcium mobilization in cultured vascular smooth muscle cells. In aortic and mesenteric smooth muscle cells isolated from male Sprague–Dawley rats, TRPC4 expression was decreased after 5 h stretch and remained suppressed th...

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Veröffentlicht in:	Life sciences (1973) Jg. 83; H. 1; S. 29 - 34
Hauptverfasser:	Lindsey, S.H., Tribe, R.M., Songu-Mize, E.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Netherlands Elsevier Inc 04.07.2008
Schlagworte:	Animals Calcium Calcium - metabolism Capacitative calcium entry Cells, Cultured Cyclic stretch Down-Regulation Male Mechanical strain Muscle, Smooth, Vascular - cytology Muscle, Smooth, Vascular - metabolism Myocytes, Smooth Muscle - metabolism Proteasomal degradation Rats Rats, Sprague-Dawley Receptor-operated calcium entry Store-operated Stress, Mechanical TRPC TRPC Cation Channels - metabolism Proteasomal degradation Calcium Mechanical strain TRPC Cyclic stretch Store-operated Capacitative calcium entry Receptor-operated calcium entry
ISSN:	0024-3205, 1879-0631
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Abstract	We investigated whether cyclic stretch affects TRPC4 or TRPC6 expression and calcium mobilization in cultured vascular smooth muscle cells. In aortic and mesenteric smooth muscle cells isolated from male Sprague–Dawley rats, TRPC4 expression was decreased after 5 h stretch and remained suppressed through 24 h stretch. After removal of the stretch stimulus, TRPC4 expression recovered within 2 h. Stretch did not affect TRPC6 expression. Stretch also decreased capacitative calcium entry, while agonist-induced calcium influx was increased. Similar results were obtained in primary aortic smooth muscle cells. TRPC4 mRNA levels were not decreased in response to mechanical strain. TRPC4 downregulation was also achieved by increasing extracellular calcium and was attenuated by gadolinium and MG132, suggesting that TRPC4 protein is regulated by intracellular calcium concentration and/or the ubiquitin-proteasome pathway. These data suggest that stretch-induced downregulation of TRPC4 protein expression and capacitative calcium entry may be a protective mechanism to offset stretch-induced increases in intracellular calcium.
AbstractList	We investigated whether cyclic stretch affects TRPC4 or TRPC6 expression and calcium mobilization in cultured vascular smooth muscle cells. In aortic and mesenteric smooth muscle cells isolated from male Sprague-Dawley rats, TRPC4 expression was decreased after 5 h stretch and remained suppressed through 24 h stretch. After removal of the stretch stimulus, TRPC4 expression recovered within 2 h. Stretch did not affect TRPC6 expression. Stretch also decreased capacitative calcium entry, while agonist-induced calcium influx was increased. Similar results were obtained in primary aortic smooth muscle cells. TRPC4 mRNA levels were not decreased in response to mechanical strain. TRPC4 downregulation was also achieved by increasing extracellular calcium and was attenuated by gadolinium and MG132, suggesting that TRPC4 protein is regulated by intracellular calcium concentration and/or the ubiquitin- proteasome pathway. These data suggest that stretch-induced downregulation of TRPC4 protein expression and capacitative calcium entry may be a protective mechanism to offset stretch-induced increases in intracellular calcium. We investigated whether cyclic stretch affects TRPC4 or TRPC6 expression and calcium mobilization in cultured vascular smooth muscle cells. In aortic and mesenteric smooth muscle cells isolated from male Sprague–Dawley rats, TRPC4 expression was decreased after 5 h stretch and remained suppressed through 24 h stretch. After removal of the stretch stimulus, TRPC4 expression recovered within 2 h. Stretch did not affect TRPC6 expression. Stretch also decreased capacitative calcium entry, while agonist-induced calcium influx was increased. Similar results were obtained in primary aortic smooth muscle cells. TRPC4 mRNA levels were not decreased in response to mechanical strain. TRPC4 downregulation was also achieved by increasing extracellular calcium and was attenuated by gadolinium and MG132, suggesting that TRPC4 protein is regulated by intracellular calcium concentration and/or the ubiquitin-proteasome pathway. These data suggest that stretch-induced downregulation of TRPC4 protein expression and capacitative calcium entry may be a protective mechanism to offset stretch-induced increases in intracellular calcium. We investigated whether cyclic stretch affects TRPC4 or TRPC6 expression and calcium mobilization in cultured vascular smooth muscle cells. In aortic and mesenteric smooth muscle cells isolated from male Sprague-Dawley rats, TRPC4 expression was decreased after 5 h stretch and remained suppressed through 24 h stretch. After removal of the stretch stimulus, TRPC4 expression recovered within 2 h. Stretch did not affect TRPC6 expression. Stretch also decreased capacitative calcium entry, while agonist-induced calcium influx was increased. Similar results were obtained in primary aortic smooth muscle cells. TRPC4 mRNA levels were not decreased in response to mechanical strain. TRPC4 downregulation was also achieved by increasing extracellular calcium and was attenuated by gadolinium and MG132, suggesting that TRPC4 protein is regulated by intracellular calcium concentration and/or the ubiquitin-proteasome pathway. These data suggest that stretch-induced downregulation of TRPC4 protein expression and capacitative calcium entry may be a protective mechanism to offset stretch-induced increases in intracellular calcium.We investigated whether cyclic stretch affects TRPC4 or TRPC6 expression and calcium mobilization in cultured vascular smooth muscle cells. In aortic and mesenteric smooth muscle cells isolated from male Sprague-Dawley rats, TRPC4 expression was decreased after 5 h stretch and remained suppressed through 24 h stretch. After removal of the stretch stimulus, TRPC4 expression recovered within 2 h. Stretch did not affect TRPC6 expression. Stretch also decreased capacitative calcium entry, while agonist-induced calcium influx was increased. Similar results were obtained in primary aortic smooth muscle cells. TRPC4 mRNA levels were not decreased in response to mechanical strain. TRPC4 downregulation was also achieved by increasing extracellular calcium and was attenuated by gadolinium and MG132, suggesting that TRPC4 protein is regulated by intracellular calcium concentration and/or the ubiquitin-proteasome pathway. These data suggest that stretch-induced downregulation of TRPC4 protein expression and capacitative calcium entry may be a protective mechanism to offset stretch-induced increases in intracellular calcium.
Author	Songu-Mize, E. Tribe, R.M. Lindsey, S.H.
Author_xml	– sequence: 1 givenname: S.H. surname: Lindsey fullname: Lindsey, S.H. email: salindse@wfubmc.edu organization: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, 1901 Perdido Street, P7-1, New Orleans, LA, 70112, United States – sequence: 2 givenname: R.M. surname: Tribe fullname: Tribe, R.M. organization: Maternal & Fetal Research Unit, Division of Reproduction and Endocrinology, King's College London, St Thomas' Hospital Campus, London, SE1 7EH, UK – sequence: 3 givenname: E. surname: Songu-Mize fullname: Songu-Mize, E. organization: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, 1901 Perdido Street, P7-1, New Orleans, LA, 70112, United States
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Keywords	Proteasomal degradation Calcium Mechanical strain TRPC Cyclic stretch Store-operated Capacitative calcium entry Receptor-operated calcium entry
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Snippet	We investigated whether cyclic stretch affects TRPC4 or TRPC6 expression and calcium mobilization in cultured vascular smooth muscle cells. In aortic and...
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SubjectTerms	Animals Calcium Calcium - metabolism Capacitative calcium entry Cells, Cultured Cyclic stretch Down-Regulation Male Mechanical strain Muscle, Smooth, Vascular - cytology Muscle, Smooth, Vascular - metabolism Myocytes, Smooth Muscle - metabolism Proteasomal degradation Rats Rats, Sprague-Dawley Receptor-operated calcium entry Store-operated Stress, Mechanical TRPC TRPC Cation Channels - metabolism
Title	Cyclic stretch decreases TRPC4 protein and capacitative calcium entry in rat vascular smooth muscle cells
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