Alterations in protein kinase C isoenzyme expression and autophosphorylation during the progression of pressure overload-induced left ventricular hypertrophy

Bayer, Allison L.; Heidkamp, Maria C.; Patel, Nilamkumar; Porter, Michael; Engman, Steve; Samarel, Allen M.

doi:10.1007/978-1-4757-4712-6_19

Cited by 24 publications

(29 citation statements)

References 24 publications

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“…21 Moreover, increased wall stretch, angiotensin II, and hypertension per se are known to increase protein kinase C activity. [22][23][24][25] Without a doubt, the impact of renovascular hypertension on endothelium-dependent relaxation was small in the present study compared with previous observations in humans 11 and rats. 21 However, it is well known that mice are less susceptible to endothelial dysfunction than, for example, rats.…”

Section: Discussionmentioning

confidence: 52%

gp91phox-Containing NADPH Oxidase Mediates Endothelial Dysfunction in Renovascular Hypertension

et al. 2004

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Background-Isoforms of the NADPH oxidase contribute to vascular superoxide anion ( · O 2 Ϫ ) formation and limit NO bioavailability. We hypothesized that the endothelial gp91phox-containing NADPH oxidase is predominant in generating the O 2 Ϫ to scavenge endothelial NO and thus is responsible for the development of endothelial dysfunction. Methods and Results-Endothelial dysfunction was studied in aortic rings from wild-type (WT) and gp91phox-knockout (gp91phox Ϫ/Ϫ ) mice with and without renovascular hypertension induced by renal artery clipping (2K1C). Hypertension induced by 2K1C was more severe in WT than in gp91phox Ϫ/Ϫ mice (158Ϯ2 versus 149Ϯ2 mm Hg; PϽ0.05). Endothelium-dependent relaxation to acetylcholine (ACh) was attenuated in rings from clipped WT but not from clipped gp91phox Ϫ/Ϫ mice. The reactive oxygen species (ROS) scavenger Tiron, PEG-superoxide dismutase, and the NADPH oxidase inhibitory peptide gp91ds-tat enhanced ACh-induced relaxation in aortae of clipped WT mice. Inhibition of protein kinase C, Rac, and the epidermal growth factor receptor kinase, elements involved in the activation of the NADPH oxidase, restored normal endothelium-dependent relaxation in vessels from clipped WT mice but had no effect on relaxations in those from gp91phox Ϫ/Ϫ mice. Relaxations to exogenous NO were attenuated in vessels from clipped WT but not clipped gp91phox Ϫ/Ϫ mice. After removal of the endothelium or treatment with PEG-superoxide dismutase, NO-induced relaxations were identical in vessels from clipped and sham-operated WT and gp91phox mice. Conclusions-These data indicate that the formation of O 2Ϫ by the endothelial gp91phox-containing NADPH oxidase accounts for the reduced NO bioavailability in the 2K1C model and contributes to the development of renovascular hypertension and endothelial dysfunction.

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Section: Discussionmentioning

confidence: 52%

gp91phox-Containing NADPH Oxidase Mediates Endothelial Dysfunction in Renovascular Hypertension

et al. 2004

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“…As increased phosphorylation of S279 reflects an increase in the amount of PKCe that can be fully activated by lipid second messengers (Saitoh et al, 2001;Bayer et al, 2003;Zhou et al, 2003;Olive et al, 2005), these results suggest that ethanol stimulates a signaling cascade that increases the pool size of fully phosphorylated PKCe in the cerebellum. Although ethanol-stimulated PKCe phosphorylation at S729 in wildtype mice, we were only able to measure this increase 60 min following ethanol injection and not at 30 min or earlier time points.…”

Section: Discussionmentioning

confidence: 81%

“…Phosphorylation at S729 permits full activity of PKCe when the enzyme is stimulated by lipid second messengers (Parekh et al, 1999;Takahashi et al, 2000). Thus, PKCe phosphorylation at S729 has been used as a marker for activation and posttranslational processing of the immature pool of PKCe that is not yet fully phosphorylated (Saitoh et al, 2001;Bayer et al, 2003;Zhou et al, 2003;Olive et al, 2005). Therefore, we used a phospho-specific antibody that detects phosphorylation of PKCe at S729 to investigate the regulation of the immature PKCe pool by ethanol.…”

Section: Ethanol Treatment Increases Pkce S729 Phosphorylation In Thementioning

confidence: 99%

Acute Functional Tolerance to Ethanol Mediated by Protein Kinase Cɛ

Wallace

Newton

Oyasu

et al. 2006

Neuropsychopharmacol

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A low level of response to ethanol is associated with increased risk of alcoholism. A major determinant of the level of response is the capacity to develop acute functional tolerance (AFT) to ethanol during a single drinking session. Mice lacking protein kinase C epsilon (PKCe) show increased signs of ethanol intoxication and reduced ethanol self-administration. Here, we report that AFT to the motorimpairing effects of ethanol is reduced in PKCe (À/À) mice when compared with wild-type littermates. In wild-type mice, in vivo ethanol exposure produced AFT that was accompanied by increased phosphorylation of PKCe and resistance of GABA A receptors to ethanol. In contrast, in PKCe (À/À) mice, GABA A receptor sensitivity to ethanol was unaltered by acute in vivo ethanol exposure. Both PKCe (À/À) and PKCe ( + / + ) mice developed robust chronic tolerance to ethanol, but the presence of chronic tolerance did not change ethanol preference drinking. These findings suggest that ethanol activates a PKCe signaling pathway that contributes to GABA A receptor resistance to ethanol and to AFT. AFT can be genetically dissociated from chronic tolerance, which is not regulated by PKCe and does not alter PKCe modulation of ethanol preference.

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“…TAC for 1 week increased the protein levels of full-length phospho-PKCδ in ABKO and WT myocardium by 257% and 240% versus the respective shams (P < 0.05; Figure 5C and Table 1). Others also see an increase in phospho-PKCδ levels after pressure overload (32). Cleaved phospho-PKCδ, presumed to reflect caspase activation, was somewhat higher in hearts from sham-operated ABKO mice (176% versus WT, P < 0.05).…”

Section: Figurementioning

confidence: 94%

1-Adrenergic receptors prevent a maladaptive cardiac response to pressure overload

OʼConnell

Swigart²,

Rodrigo

et al. 2006

Journal of Clinical Investigation

130

139

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An α 1 -adrenergic receptor (α 1 -AR) antagonist increased heart failure in the Antihypertensive and LipidLowering Treatment to Prevent Heart Attack Trial (ALLHAT), but it is unknown whether this adverse result was due to α 1 -AR inhibition or a nonspecific drug effect. We studied cardiac pressure overload in mice with double KO of the 2 main α 1 -AR subtypes in the heart, α 1A (Adra1a) and α 1B (Adra1b). At 2 weeks after transverse aortic constriction (TAC), KO mouse survival was only 60% of WT, and surviving KO mice had lower ejection fractions and larger end-diastolic volumes than WT mice. Mechanistically, final heart weight and myocyte cross-sectional area were the same after TAC in KO and WT mice. However, KO hearts after TAC had increased interstitial fibrosis, increased apoptosis, and failed induction of the fetal hypertrophic genes. Before TAC, isolated KO myocytes were more susceptible to apoptosis after oxidative and β-AR stimulation, and β-ARs were desensitized. Thus, α 1 -AR deletion worsens dilated cardiomyopathy after pressure overload, by multiple mechanisms, indicating that α 1 -signaling is required for cardiac adaptation. These results suggest that the adverse cardiac effects of α 1 -antagonists in clinical trials are due to loss of α 1 -signaling in myocytes, emphasizing concern about clinical use of α 1 -antagonists, and point to a revised perspective on sympathetic activation in heart failure.

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Alterations in protein kinase C isoenzyme expression and autophosphorylation during the progression of pressure overload-induced left ventricular hypertrophy

Cited by 24 publications

References 24 publications

gp91phox-Containing NADPH Oxidase Mediates Endothelial Dysfunction in Renovascular Hypertension

gp91phox-Containing NADPH Oxidase Mediates Endothelial Dysfunction in Renovascular Hypertension

Acute Functional Tolerance to Ethanol Mediated by Protein Kinase Cɛ

1-Adrenergic receptors prevent a maladaptive cardiac response to pressure overload

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