A single transient episode of hyperammonemia induces long-lasting alterations in protein kinase A

2007 ◽  
Vol 292 (1) ◽  
pp. G305-G314 ◽  
Author(s):  
Carmina Montoliu ◽  
Blanca Piedrafita ◽  
Miguel A. Serra ◽  
Juan A. del Olmo ◽  
José M. Rodrigo ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Hepatic Encephalopathy ◽  
Protein Kinase ◽  
Blood Cells ◽  
Poor Prognosis ◽  
Regulatory Subunit ◽  
Portacaval Anastomosis ◽  
The Poor ◽  
Cirrhotic Patients ◽  
Transient Episode

Hepatic encephalopathy in patients with liver disease is associated with poor prognosis. This could be due to the induction by the transient episode of hepatic encephalopathy of long-lasting alterations making patients more susceptible. We show that a single transient episode of hyperammonemia induces long-lasting alterations in signal transduction. The content of the regulatory subunit of the protein kinase dependent on cAMP (PKA-RI) is increased in erythrocytes from cirrhotic patients. This increase is reproduced in rats with portacaval anastomosis and in rats with hyperammonemia without liver failure, suggesting that hyperammonemia is responsible for increased PKA-RI in patients. We analyzed whether there is a correlation between ammonia levels and PKA-RI content in patients. All cirrhotic patients had increased content of PKA-RI. Some of them showed normal ammonia levels but had suffered previous hyperammonemia episodes. This suggested that a single transient episode of hyperammonemia could induce the long-lasting increase in PKA-RI. To assess this, we injected normal rats with ammonia and blood was taken at different times. Ammonia returned to basal levels at 2 h. However, PKA-RI was significantly increased in blood cells from rats injected with ammonia 3 wk after injection. In conclusion, it is shown that a single transient episode of hyperammonemia induces long-lasting alterations in signal transduction both in blood and brain. These alterations may contribute to the poor prognosis of patients suffering hepatic encephalopathy.

scholarly journals Transgenic Inhibitors Identify Two Roles for Protein Kinase A in Drosophila Development

Genetics ◽  
1999 ◽  
Vol 152 (1) ◽  
pp. 281-290 ◽  
Author(s):  
John A Kiger ◽  
Jennifer L Eklund ◽  
Susan H Younger ◽  
Cahir J O’Kane
Keyword(s):  
Signal Transduction ◽  
Protein Kinase ◽  
Pattern Formation ◽  
Protein Kinase A ◽  
Hedgehog Signaling ◽  
Growth Regulation ◽  
Larval Growth ◽  
Competitive Inhibitor ◽  
Regulatory Subunit ◽  
Kinase A

Abstract We have initiated an analysis of protein kinase A (PKA) in Drosophila using transgenic techniques to modulate PKA activity in specific tissues during development. We have constructed GAL4/UAS-regulated transgenes in active and mutant forms that encode PKAc, the catalytic subunit of PKA, and PKI(1-31), a competitive inhibitor of PKAc. We present evidence that the wild-type transgenes are active and summarize the phenotypes produced by a number of GAL4 enhancer-detector strains. We compare the effects of transgenes encoding PKI(1-31) with those encoding PKAr*, a mutant regulatory subunit that constitutively inhibits PKAc because of its inability to bind cyclic AMP. Both inhibitors block larval growth, but only PKAr* alters pattern formation by activating the Hedgehog signaling pathway. Therefore, transgenic PKI(1-31) should provide a tool to investigate the role of PKAc in larval growth regulation without concomitant changes in pattern formation. The different effects of PKI(1-31) and PKAr* suggest two distinct roles, cytoplasmic and nuclear, for PKAc in Hedgehog signal transduction. Alternatively, PKAr* may target proteins other than PKAc, suggesting a role for free PKAr in signal transduction, a role inhibited by PKAc in reversal of the classical relationship of these subunits.

Regulation of spontaneous and induced resumption of meiosis in mouse oocytes by different intracellular pathways

Reproduction ◽  
2000 ◽  
pp. 377-383 ◽  
Author(s):  
L Leonardsen ◽  
A Wiersma ◽  
M Baltsen ◽  
AG Byskov ◽  
CY Andersen
Keyword(s):  
Signal Transduction ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Mitogen Activated Protein Kinase ◽  
Meiotic Maturation ◽  
Mouse Oocytes ◽  
Mitogen Activated Protein ◽  
Dependent Signal ◽  
Kinase Pathway ◽  
Kinase A

The mitogen-activated protein kinase-dependent and the cAMP-protein kinase A-dependent signal transduction pathways were studied in cultured mouse oocytes during induced and spontaneous meiotic maturation. The role of the mitogen-activated protein kinase pathway was assessed using PD98059, which specifically inhibits mitogen-activated protein kinase 1 and 2 (that is, MEK1 and MEK2), which activates mitogen-activated protein kinase. The cAMP-dependent protein kinase was studied by treating oocytes with the protein kinase A inhibitor rp-cAMP. Inhibition of the mitogen-activated protein kinase pathway by PD98059 (25 micromol l(-1)) selectively inhibited the stimulatory effect on meiotic maturation by FSH and meiosis-activating sterol (that is, 4,4-dimethyl-5alpha-cholest-8,14, 24-triene-3beta-ol) in the presence of 4 mmol hypoxanthine l(-1), whereas spontaneous maturation in the absence of hypoxanthine was unaffected. This finding indicates that different signal transduction mechanisms are involved in induced and spontaneous maturation. The protein kinase A inhibitor rp-cAMP induced meiotic maturation in the presence of 4 mmol hypoxanthine l(-1), an effect that was additive to the maturation-promoting effect of FSH and meiosis-activating sterol, indicating that induced maturation also uses the cAMP-protein kinase A-dependent signal transduction pathway. In conclusion, induced and spontaneous maturation of mouse oocytes appear to use different signal transduction pathways.

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