PARADOXICAL STIMULATORY EFFECT OF THE KINASE INHIBITOR CHELERYTHRINE ON THE PHOSPHORYLATION OF A SIMILAR-TO-20-K M(R) PROTEIN PRESENT IN THE MITOCHONDRIAL-FRACTION OF RAT RETINA
Jb. Lombardini, PARADOXICAL STIMULATORY EFFECT OF THE KINASE INHIBITOR CHELERYTHRINE ON THE PHOSPHORYLATION OF A SIMILAR-TO-20-K M(R) PROTEIN PRESENT IN THE MITOCHONDRIAL-FRACTION OF RAT RETINA, Brain research, 673(2), 1995, pp. 194-198
In order to characterize the phosphorylation of a similar to 20k M(r)
protein present in the mitochondrial fraction of the rat retina, chele
rythrine chloride, a well-known protein kinase C inhibitor, was tested
for activity. Instead of the expected inhibition of the kinase reacti
on by chelerythrine the phosphorylation of the similar to 20k M(r) pro
tein was stimulated by a factor of 3 at 150 mu M. This unique stimulat
ory action of chelerythrine could be eliminated by the addition of 10
mM dithiothreitol. A suggested mechanism of action for dithiothreitol
in the elimination of the increased phosphorylation of the similar to
20k M(r) protein by chelerythrine is the addition of the thiol group o
f dithiothreitol to the iminium bond of chelerythrine. Taurine, a know
n inhibitor of the phosphorylation of retinal proteins was also tested
in combination with chelerythrine for its effects on the phosphorylat
ion of the similar to 20k M(r) protein. A non-competitive relationship
was observed when chelerytrhine was used as the variable activator an
d taurine as the fixed inhibitor (30 mM). The stimulatory effect of ch
elerythrine on the phosphorylation of proteins was not limited to reti
nal tissue but was also observed in the P-2 fraction of brain cortex.
Chelerythrine demonstrated only inhibitory effects on the phosphorylat
ion of proteins in a heart mitochondrial fraction.