Abstract
ABSTRACT: Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C) is widely distributed in mammalian tissues. Accumulating evidence has revealed that protein kinase C as well as cAMP-dependent protein kinase plays important roles in various cellular functions. The purpose of this study is to examine the effect of bilirubin on protein kinase C and cAMP-dependent protein kinase activity in a cell-free system as a cause of bilirubin toxicity to the central nervous system. Bilirubin inhibited protein kinase C activity in a dose-dependent manner. This effect was markedly diminished by the addition of human serum albumin at a molar ratio of bilirubin to albumin of less than 1.0. Kinetic analysis revealed that bilirubin did not compete with phospholipid, diacylglycerol, or calcium. Bilirubin also inhibited cAMP-dependent protein kinase, but did not compete with cAMP. The inhibitory effect of bilirubin on protein kinase C seems to be irreversible because removal of bilirubin by Sephadex G-25 column chromatography did not restore the protein kinase C activity. Observations reported herein suggest that bilirubin, especially in its free form, induces an irreversible change to the catalytically active site of protein kinase C.
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Sano, K., Nakamura, H. & Matsuo, T. Mode of Inhibitory Action of Bilirubin on Protein Kinase C. Pediatr Res 19, 587–590 (1985). https://doi.org/10.1203/00006450-198506000-00017
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DOI: https://doi.org/10.1203/00006450-198506000-00017
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