Minimally modified low density lipoproteins induce aortic smooth muscle cell proliferation via the activation of mitogen activated protein kinase.
We have investigated the effects of modifying LDL by Cu++ and various hemoglobin preparations on aortic smooth muscle cell proliferation and on the activation of mitogen activated protein kinase. We found that at very low concentrations (10 microg/ml), LDL modified by all of the above agonists markedly stimulated cell proliferation (5-10 fold). This was accompanied by a 2-3 fold stimulation in mitogen activated protein kinase (MAPK) activity. We conclude that modification of LDL under situations that are closer to those found in vivo (i.e. hypoxic conditions), may involve the activation of MAPK as a common biochemical mechanism of action. This in turn, contributes to aortic smooth muscle cell proliferation.
Balagopalakrishna
C
C
Laboratory of Cellular and Molecular Biology, National Institutes of Health, National Institute on Aging, Baltimore, Maryland, USA.
Bhunia
A K
AK
Rifkind
J M
JM
Chatterjee
S
S
D000818:Animals; D001011:Aorta; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D003300:Copper / Q000494:pharmacology; D004789:Enzyme Activation; D006454:Hemoglobins / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D008706:Methemoglobin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010108:Oxyhemoglobins / Q000494:pharmacology; D011817:Rabbits
D006454:Hemoglobins; D008077:Lipoproteins, LDL; D010108:Oxyhemoglobins; D003300:Copper; D008706:Methemoglobin; D017871:Calcium-Calmodulin-Dependent Protein Kinases