Regulation of catalase enzyme activity by cell signaling molecules.
Mitogenic cell proliferation requires a rapid and transient H2O2 generation, which is blocked by catalase or PKA activators. Previously, we observed that anemic HIV(+) individuals expressed acidic pIs of catalase in RBC with significantly high activities [Mol Cell Biochem 165: 77-81, 1996]. These findings led us to hypothesize that cell signaling molecules regulate catalase to control cell mitogenesis. To test the hypothesis, we determined (i) whether RBC counts correlate with their catalase activities, (ii) whether protein kinases and phosphatases alter catalase activity in vitro, and (iii) whether protein kinase activators increase catalase activity to suppress proliferation of cultured cells. The results indicated that RBC counts inversely correlated with RBC catalase activities in both HIV(+) (r: -0.6769, r2: 0.4582, n: 69 male, p < 0.0001) and HIV(-) (r: -0.3827, r2: 0.1464, n: 177 male, p < 0.0001) populations. Catalytic PKA, PKC and Casein Kinase II, but none of PKG, Ca2+/calmodulin kinase II and p34cdc/cyclinB, rapidly elevated catalase activity in vitro by up to 2-fold. Whereas a major CAT subunit (60 kDa) showed immunoreactive phosphoserine and phosphothreonine, the kinases- and gamma-32P-ATP-dependent phosphorylation occurred with a minor component (110 kDa). Among PKC isozymes examined, PKCzeta was the most effective modulator followed by PKCgamma, and protein phosphatase 1gamma and 2A decreased the catalase activity. PKA and PKCzeta activators of forskolin and okadaic acid increased catalase activity and 110 kDa expression in NIH3T3 cells up to 2.4-fold and suppressed the cell growth, showing an inverse correlation of the indices (r: -0.9286, r2: 0.8622, n: 18, p < 0.0001). Taken together, these results suggest for the first time that catalase is under the regulation of cell signaling molecules and capable of modulating mitogenic cell proliferation.
Yano
Sumio
S
Department of Biochemistry, Ponce School of Medicine, Ponce, Puerto Rico, USA. yanos@coqui.net
Yano
Noriko
N
D016475:3T3 Cells; D000328:Adult; D000818:Animals; D015153:Blotting, Western; D002374:Catalase / Q000097:blood* / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D006678:HIV / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D008938:Mitosis; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction
D006861:Hydrogen Peroxide; D002374:Catalase; D011494:Protein Kinases