| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 145, 1265-1270, Copyright © 1994 by American Society for Investigative Pathology
REGULAR ARTICLES |
D Leszczynski, Y Zhao, M Luokkamaki and ML Foegh
Department of Research, Finnish Centre for Radiation and Nuclear Safety, Helsinki.
We examined the effect of several inhibitors/activators of various protein kinases on the proliferation and apoptosis of nontransformed rat coronary vascular smooth muscle cells (SMC). As expected, all the compounds (calphostin C, KT5720, KT5823, verapamil, W7, and dibutyryl- cAMP) inhibited SMC proliferation, as judged by [3H]thymidine incorporation. Three (calphostin C, verapamil and dibutyryl-cAMP) of the six compounds caused occurrence of the classical apoptotic morphology in SMC. The effect of calphostin C, an inhibitor of protein kinase C, was examined in more detail due to the known involvement of this kinase in regulation of apoptosis in a variety of cell types. In SMC cultures exposed for 1, 2, and 3 days to 0.1 mumol/L calphostin C, 7 +/- 1%, 32 +/- 3%, and 29 +/- 3% of cells underwent apoptosis, respectively, as assessed by cell morphology (control cultures had 1 to 3% of apoptotic cells). The effect of calphostin C was transient in that on day 6 following exposure to this compound the number of apoptotic cells declined to control values. Simultaneous with the induction of apoptotic morphology in SMC, a decline was seen (within 24 hours) in expression of the oncoprotein Bcl-2 in morphologically nonapoptotic SMC. An altered distribution of Bcl-2 was seen in the apoptotic cells. The calphostin C-induced generation of apoptotic cells in SMC cultures and the decline/alteration of Bcl-2 expression were not accompanied by degradation of DNA into nucleosomal fragments. In conclusion, normal, nontransformed rat coronary artery vascular SMC undergo apoptosis when exposed to an inhibitor of protein kinase C (calphostin C), to a calcium channel blocker (verapamil), and to a stimulator of cAMP-dependent protein kinase (dibutyryl-cAMP). The induction of apoptosis by the inhibitor of protein kinase C is accompanied by alterations in the Bcl-2 expression but not by DNA fragmentation.
This article has been cited by other articles:
 |
|
 |
|
  X.-L. Zheng, Y. Gui, G. Du, M. A. Frohman, and D.-Q. Peng Calphostin-C Induction of Vascular Smooth Muscle Cell Apoptosis Proceeds through Phospholipase D and Microtubule Inhibition J. Biol. Chem., February 20, 2004; 279(8): 7112 - 7118. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-J. Gao, H. Yang, K. Teoh, and R. M.K.W. Lee Detrimental effects of papaverine on the human internal thoracic artery J. Thorac. Cardiovasc. Surg., July 1, 2003; 126(1): 179 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sakuma, M. Yamamoto, M. Okumura, T. Kojima, T. Maruyama, and K. Yasuda High glucose inhibits apoptosis in human coronary artery smooth muscle cells by increasing bcl-xL and bfl-1/A1 Am J Physiol Cell Physiol, August 1, 2002; 283(2): C422 - C428. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. D. Intengan and E. L. Schiffrin Vascular Remodeling in Hypertension: Roles of Apoptosis, Inflammation, and Fibrosis Hypertension, September 1, 2001; 38(3): 581 - 587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Salvi Protecting the Myocardium From Ischemic Injury : A Critical Role for {{alpha}}1-Adrenoreceptors? Chest, April 1, 2001; 119(4): 1242 - 1249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Hall, C. M. Matter, X. Wang, and G. H. Gibbons Hyperglycemia Inhibits Vascular Smooth Muscle Cell Apoptosis Through a Protein Kinase C-Dependent Pathway Circ. Res., September 29, 2000; 87(7): 574 - 580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-L. Peyot, A.-P. Gadeau, F. Dandre, I. Belloc, F. Dupuch, and C. Desgranges Extracellular Adenosine Induces Apoptosis of Human Arterial Smooth Muscle Cells via A2b-Purinoceptor Circ. Res., January 7, 2000; 86(1): 76 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Das, E. C. Dempsey, D. Bouchey, M. E. Reyland, and K. R. Stenmark Chronic Hypoxia Induces Exaggerated Growth Responses in Pulmonary Artery Adventitial Fibroblasts . Potential Contribution of Specific Protein Kinase C Isozymes Am. J. Respir. Cell Mol. Biol., January 1, 2000; 22(1): 15 - 25. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. P. Mason Calcium channel blockers, apoptosis and cancer: is there a biologic relationship? J. Am. Coll. Cardiol., December 1, 1999; 34(7): 1857 - 1866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. N. Diep, J.-S. Li, and E. L. Schiffrin In Vivo Study of AT1 and AT2 Angiotensin Receptors in Apoptosis in Rat Blood Vessels Hypertension, October 1, 1999; 34(4): 617 - 624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-F. Li, C. Maasch, H. Haller, R. Dietz, and R. von Harsdorf Requirement for Protein Kinase C in Reactive Oxygen Species–Induced Apoptosis of Vascular Smooth Muscle Cells Circulation, August 31, 1999; 100(9): 967 - 973. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Salvi {alpha}1-Adrenergic Hypothesis for Pulmonary Hypertension Chest, June 1, 1999; 115(6): 1708 - 1719. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Lizard, S. Monier, C. Cordelet, L. Gesquiere, V. Deckert, S. Gueldry, L. Lagrost, and P. Gambert Characterization and Comparison of the Mode of Cell Death, Apoptosis Versus Necrosis, Induced by 7ß-Hydroxycholesterol and 7-Ketocholesterol in the Cells of the Vascular Wall Arterioscler. Thromb. Vasc. Biol., May 1, 1999; 19(5): 1190 - 1200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Tohda, K. Oida, Y. Okada, S. Kosaka, E. Okada, S. Takahashi, H. Ishii, and I. Miyamori Expression of Thrombomodulin in Atherosclerotic Lesions and Mitogenic Activity of Recombinant Thrombomodulin in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., December 1, 1998; 18(12): 1861 - 1869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shichiri, H. Kato, F. Marumo, and Y. Hirata Endothelin-1 as an Autocrine/Paracrine Apoptosis Survival Factor for Endothelial Cells Hypertension, November 1, 1997; 30(5): 1198 - 1203. [Abstract] [Full Text]
|
|
|
|
|
|
S. Jovinge, M. Crisby, J. Thyberg, and J. Nilsson DNA Fragmentation and Ultrastructural Changes of Degenerating Cells in Atherosclerotic Lesions and Smooth Muscle Cells Exposed to Oxidized LDL in Vitro Arterioscler. Thromb. Vasc. Biol., October 1, 1997; 17(10): 2225 - 2231. [Abstract] [Full Text]
|
|
|
|
|
|
J. Diez, A. Panizo, M. Hernandez, and J. Pardo Is the Regulation of Apoptosis Altered in Smooth Muscle Cells of Adult Spontaneously Hypertensive Rats? Hypertension, March 1, 1997; 29(3): 776 - 780. [Abstract] [Full Text]
|
|
|
|
|
|
D. deBlois, B.-S. Tea, T.-V. Dam, J. Tremblay, and P. Hamet Smooth Muscle Apoptosis During Vascular Regression in Spontaneously Hypertensive Rats Hypertension, January 1, 1997; 29(1): 340 - 344. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Misao, Y. Hayakawa, M. Ohno, S. Kato, T. Fujiwara, and H. Fujiwara Expression of bcl-2 Protein, an Inhibitor of Apoptosis, and Bax, an Accelerator of Apoptosis, in Ventricular Myocytes of Human Hearts With Myocardial Infarction Circulation, October 1, 1996; 94(7): 1506 - 1512. [Abstract] [Full Text]
|
|
|
|
|
|
M. M. Kockx, G. R.Y. De Meyer, H. Bortier, N. de Meyere, J. Muhring, A. Bakker, W. Jacob, L. Van Vaeck, and A. Herman Luminal Foam Cell Accumulation Is Associated With Smooth Muscle Cell Death in the Intimal Thickening of Human Saphenous Vein Grafts Circulation, September 15, 1996; 94(6): 1255 - 1262. [Abstract] [Full Text]
|
|
|
|
|
|
B. Bjorkerud and S. Bjorkerud Contrary Effects of Lightly and Strongly Oxidized LDL With Potent Promotion of Growth Versus Apoptosis on Arterial Smooth Muscle Cells, Macrophages, and Fibroblasts Arterioscler. Thromb. Vasc. Biol., March 1, 1996; 16(3): 416 - 424. [Abstract] [Full Text]
|
|
|
|
|
|
J. M. Isner, M. Kearney, S. Bortman, and J. Passeri Apoptosis in Human Atherosclerosis and Restenosis Circulation, June 1, 1995; 91(11): 2703 - 2711. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
