© 1999 American Heart Association, Inc.
Original Contribution |
Two Distinct Mechanisms Mediate a Differential Regulation of Protein Kinase C Isozymes in Acute and Prolonged Myocardial Ischemia
From the Department of Cardiology, Angiology, and Pulmology, University of Heidelberg, Medical Center, Heidelberg, Germany.
Correspondence to Ruth H. Strasser, Department of Cardiology, Angiology, and Pulmology, University of Heidelberg, Bergheimer Str 58, 69115 Heidelberg, Germany. E-mail ruth.strasser{at}med.uni-heidelberg.de
Abstract—An activation of
protein kinase C (PKC) in acute myocardial ischemia has been
shown previously using its translocation to the plasma membrane as an
indirect parameter. However, whether PKC remains
activated or whether other mechanisms such as altered gene
expression may mediate an isozyme-specific regulation in prolonged
ischemia have not been investigated. In isolated perfused rat
hearts, PKC activity and the expression of PKC cardiac isozymes were
determined on the protein level using enzyme activities and Western
blot analyses and on the mRNA level using reverse
transcriptase–polymerase chain reaction after various periods of
global ischemia (1 to 60 minutes). As early as 1 minute after
the onset of ischemia, PKC activity is translocated from the
cytosol to the particulate fraction without change in total cardiac
enzyme activity. This translocation involves all major cardiac isozymes
of PKC (ie, PKC
, PKC
, PKC
, and PKC
). This rapid,
nonselective activation of PKCs is only transient. In contrast,
prolonged ischemia (
15 minutes) leads to an increased cardiac
PKC activity (119±7 versus 190±8 pmol/min per mg protein) residing in
the cytosol. This is associated with an augmented, subtype-selective
isozyme expression of PKC and PKC (163% and 199%,
respectively). The specific mRNAs for PKC (948±83 versus 1501±138
ag/ng total RNA, 30 minutes of ischemia) and PKC (1597±166
versus 2611±252 ag/ng total RNA) are selectively increased. PKC and
PKC remain unaltered. In conclusion, two distinct activation and
regulation processes of PKC are characterized in acute myocardial
ischemia. The early, but transient, translocation involves all
constitutively expressed cardiac isozymes of PKC, whereas in prolonged
ischemia an increased total PKC activity is associated with an
isozyme-selective induction of PKC and PKC. Whether these
fundamentally different activation processes interact remains to
be elucidated.
Key Words: acute myocardial ischemia • protein kinase C • heart • signal transduction
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