Inhibitory effects of omega-3 fatty acids on protein kinase C activity in vitro

Kim, H F Seung; Weeber, Edwin J.; Sweatt, J. David; Stoll, Andrew L.; Marangell, Lauren B.

doi:10.1038/sj.mp.4000837

Cited by 66 publications

(21 citation statements)

References 13 publications

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“…We found a similar effect of omega-3 FA in vitro , where the addition of EPA to human cardiomyocyte AC16 cells inhibited palmitate-induced PKC alpha activation and expression of inflammatory cytokines. These findings, in conjunction with other studies showing PKC inhibition with EPA and DHA (38), suggest that omega-3 FA enrichment of intracellular lipids can ameliorate PKC-mediated cardiac dysfunction.…”

Section: Discussionsupporting

confidence: 83%

Fish Oil Selectively Improves Heart Function in a Mouse Model of Lipid-induced Cardiomyopathy

Khan

Chokshi

Drosatos

et al. 2013

Journal of Cardiovascular Pharmacology

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Fish oil (FO) supplementation may improve cardiac function in some patients with heart failure, especially those with diabetes. To determine why this occurs, we studied the effects of FO in mice with heart failure due either to transgenic expression of the lipid uptake protein, acyl CoA synthetase 1 (ACS1) or overexpression of the transcription factor peroxisomal proliferator activated receptor (PPAR)γ via the cardiac specific myosin heavy chain (MHC) promoter. ACS1 mice and control littermates were fed three diets containing low or high-dose FO or non-purified diet (NPD) for 6 weeks. MHC-PPARγ mice were fed low-dose FO or NPD. Compared to control mice fed NPD, ACS1 and MHC-PPARγ mice fed NPD had reduced cardiac function and survival with cardiac fibrosis. In contrast, ACS1 mice fed high-dose FO had better cardiac function, survival and less myocardial fibrosis. FO increased eicosapentaenoic and docosahexaenoic acids and reduced saturated fatty acids in cardiac diacylglycerols. This was associated with reduced PKC alpha and beta activation. In contrast, low-dose FO reduced MHC-PPARγ mice survival with no change in PKC activation or cardiac function. Thus, dietary FO reverses fibrosis and improves cardiac function and survival of ACS1 mice, but does not benefit all forms of lipid-mediated cardiomyopathy.

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Section: Discussionsupporting

confidence: 83%

Fish Oil Selectively Improves Heart Function in a Mouse Model of Lipid-induced Cardiomyopathy

Khan

Chokshi

Drosatos

et al. 2013

Journal of Cardiovascular Pharmacology

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“…ω3-PUFAs affect several of these NHE-1 stimuli. They reduce diacylglycerol and PKC, activate the parasympathetic nervous system, and reduce angiotensin-converting enzyme (ACE) activity (Mohan and Das, 2001; Seung-Kim et al, 2001; Takahashi et al, 2005), although the latter is not a consistent finding (Ogawa et al, 2009). An intriguing question is why the NHE-1 activity in myocytes of ω3-PUFA fed animals is lower than in myocytes of ω9-MUFA fed animals in our model of volume- and pressure-overload, while it is not different in healthy rabbits.…”

Section: Discussionmentioning

confidence: 99%

Dietary Omega-3 Polyunsaturated Fatty Acids Suppress NHE-1 Upregulation in a Rabbit Model of Volume- and Pressure-Overload

Borren¹,

Ruijter²,

Baartscheer³

et al. 2012

Front. Physio.

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Background: Increased consumption of omega-3 polyunsaturated fatty acids (ω3-PUFAs) from fish oil (FO) may have cardioprotective effects during ischemia/reperfusion, hypertrophy, and heart failure (HF). The cardiac Na+/H+-exchanger (NHE-1) is a key mediator for these detrimental cardiac conditions. Consequently, chronic NHE-1 inhibition appears to be a promising pharmacological tool for prevention and treatment. Acute application of the FO ω3-PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) inhibit the NHE-1 in isolated cardiomyocytes. We studied the effects of a diet enriched with ω3-PUFAs on the NHE-1 activity in healthy rabbits and in a rabbit model of HF induced by volume- and pressure-overload. Methods: Rabbits were allocated to four groups. The first two groups consisted of healthy rabbits, which were fed either a diet containing 1.25% (w/w) FO (ω3-PUFAs), or 1.25% high-oleic sunflower oil (ω9-MUFAs) as control. The second two groups were also allocated to either a diet containing ω3-PUFAs or ω9-MUFAs, but underwent volume- and pressure-overload to induce HF. Ventricular myocytes were isolated by enzymatic dissociation and used for intracellular pH (pHi) and patch-clamp measurements. NHE-1 activity was measured in HEPES-buffered conditions as recovery rate from acidosis due to ammonium prepulses. Results: In healthy rabbits, NHE-1 activity in ω9-MUFAs and ω3-PUFAs myocytes was not significantly different. Volume- and pressure-overload in rabbits increased the NHE-1 activity in ω9-MUFAs myocytes, but not in ω3-PUFAs myocytes, resulting in a significantly lower NHE-1 activity in myocytes of ω3-PUFA fed HF rabbits. The susceptibility to induced delayed afterdepolarizations (DADs), a cellular mechanism of arrhythmias, was lower in myocytes of HF animals fed ω3-PUFAs compared to myocytes of HF animals fed ω9-MUFAs. In our rabbit HF model, the degree of hypertrophy was similar in the ω3-PUFAs group compared to the ω9-MUFAs group. Conclusion: Dietary ω3-PUFAs from FO suppress upregulation of the NHE-1 activity and lower the incidence of DADs in our rabbit model of volume- and pressure-overload.

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“…valproate) have not yet been undertaken. In considering the potential for these types of studies, it is important to keep in mind that valproate and sodium butyrate are non-specific inhibitors of HDACs that effect several additional targets (e.g., protein kinase C; Manji and Lenox, 1999; Seung Kim et al, 2001). Clearly, additional selective agents acting at specific HDAC isoforms (see Table 1) are needed to begin to address the question of the applicability of HDAC inhibitors for therapeutics of human cognitive dysfunction.…”

Section: Epigenetic Mechanisms In Memory Formationmentioning

confidence: 99%

An epigenetic hypothesis of aging-related cognitive dysfunction

Penner

2010

Fronti.Ag.Neurosci.

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This brief review will focus on a new hypothesis for the role of epigenetic mechanisms in aging-related disruptions of synaptic plasticity and memory. Epigenetics refers to a set of potentially self-perpetuating, covalent modifications of DNA and post-translational modifications of nuclear proteins that produce lasting alterations in chromatin structure. These mechanisms, in turn, result in alterations in specific patterns of gene expression. Aging-related memory decline is manifest prominently in declarative/episodic memory and working memory, memory modalities anatomically based largely in the hippocampus and prefrontal cortex, respectively. The neurobiological underpinnings of age-related memory deficits include aberrant changes in gene transcription that ultimately affect the ability of the aged brain to be “plastic”. The molecular mechanisms underlying these changes in gene transcription are not currently known, but recent work points toward a potential novel mechanism, dysregulation of epigenetic mechanisms. This has led us to hypothesize that dysregulation of epigenetic control mechanisms and aberrant epigenetic “marks” drive aging-related cognitive dysfunction. Here we focus on this theme, reviewing current knowledge concerning epigenetic molecular mechanisms, as well as recent results suggesting disruption of plasticity and memory formation during aging. Finally, several open questions will be discussed that we believe will fuel experimental discovery.

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Inhibitory effects of omega-3 fatty acids on protein kinase C activity in vitro

Cited by 66 publications

References 13 publications

Fish Oil Selectively Improves Heart Function in a Mouse Model of Lipid-induced Cardiomyopathy

Fish Oil Selectively Improves Heart Function in a Mouse Model of Lipid-induced Cardiomyopathy

Dietary Omega-3 Polyunsaturated Fatty Acids Suppress NHE-1 Upregulation in a Rabbit Model of Volume- and Pressure-Overload

An epigenetic hypothesis of aging-related cognitive dysfunction

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