Desmin gene expression in cardiac myocytes is responsive to contractile activity and stretch.
Experiments were performed to assess the ability of mechanical stimuli, experienced by ventricular cardiac myocytes during the progression of hypertrophic and dilated pathology, to increase the expression of desmin in cultured neonatal rat cardiac myocytes. Results indicate that both contractile activity and load due to passive stretch increase desmin content in neonatal rat cardiac myocytes through increased desmin gene transcription. Western blot analysis demonstrated that contraction induced a selective increase in desmin protein content in neonatal rat cardiac myocytes above increases observed in the content of total cellular protein. Northern blot analysis indicated that desmin mRNA content increased in response to contraction as well as to alpha-adrenergic stimulation. Desmin mRNA content also increased in cultured neonatal myocytes in response to stretch. Angiotensin II (ANG II) treatment of contracting neonatal cardiac myocytes further increased desmin mRNA content, whereas similar treatment in arrested neonatal cardiac myocytes further increased desmin mRNA content, whereas similar treatment in arrested neonatal cardiac myocytes failed to increase desmin mRNA. This contraction-dependent responsiveness to ANG II is not a function of increases in the density or relative subtype composition of ANG II receptors. Treatment of contracting neonatal rat cardiac myocytes with actinomycin D prevented increases in desmin mRNA content, suggesting regulation of transcription of the desmin gene by contraction. Nuclear run-on experiments indicate that contraction. Nuclear run-on experiments indicate that contraction increases transcription of the desmin gene in cardiac myocytes. These results are consistent with the modulation of desmin gene expression secondarily to changes in the mechanical environment that occur in cardiac tissue undergoing dilation or hypertrophy.
Watson
P A
PA
Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 17822-2615, USA.
Hannan
R
R
Carl
L L
LL
Giger
K E
KE
D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology; D003609:Dactinomycin / Q000494:pharmacology; D003893:Desmin / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D008969:Molecular Sequence Data; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D015345:Oligonucleotide Probes; D010812:Physical Stimulation; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism; D013314:Stress, Mechanical
D057911:Angiotensin Receptor Antagonists; D003893:Desmin; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D003609:Dactinomycin; D012319:RNA Polymerase II