Conjugated linoleic acid prevents high glucose-induced hypertrophy and contractile dysfunction in adult rat cardiomyocytes.

Diabetes mellitus is associated with increased risk and incidence of cardiovascular morbidity and mortality, independently of other risk factors typically associated with diabetes such as coronary artery disease and hypertension. This promotes the development of a distinct condition of the heart muscle known as diabetic cardiomyopathy. We have previously shown that conjugated linoleic acid (CLA) prevents endothelin-1-induced cardiomyocyte hypertrophy.

Liganded peroxisome proliferator-activated receptors (PPARs) preserve nuclear histone deacetylase 5 levels in endothelin-treated Sprague-Dawley rat cardiac myocytes.

Ligand activation of peroxisome proliferator-activated receptors (PPARs) prevents cardiac myocyte hypertrophy, and we previously reported that diacylglycerol kinase zeta (DGKζ) is critically involved. DGKζ is an intracellular lipid kinase that catalyzes phosphorylation of diacylglycerol; by attenuating DAG signaling, DGKζ suppresses protein kinase C (PKC) and G-protein signaling. Here, we investigated how PPAR-DGKζ signaling blocks activation of the hypertrophic gene program.

Ligand activation of cannabinoid receptors attenuates hypertrophy of neonatal rat cardiomyocytes.

: Endocannabinoids are bioactive amides, esters, and ethers of long-chain polyunsaturated fatty acids. Evidence suggests that activation of the endocannabinoid pathway offers cardioprotection against myocardial ischemia, arrhythmias, and endothelial dysfunction of coronary arteries. As cardiac hypertrophy is a convergence point of risk factors for heart failure, we determined a role for endocannabinoids in attenuating endothelin-1-induced hypertrophy and probed the signaling pathways involved.

Suppression of endothelin-1-induced cardiac myocyte hypertrophy by PPAR agonists: role of diacylglycerol kinase zeta.

Aims: Ligand activation of peroxisome proliferator-activated receptors (PPARs) prevents cardiomyocyte hypertrophy, but the underlying signalling mechanisms remain unknown. We previously reported that the anti-hypertrophic effect of the dietary polyunsaturated fatty acid, conjugated linoleic acid (CLA), was associated with the upregulation of diacylglycerol (DAG) kinase (DGK). DGK catalyses phosphorylative conversion/attenuation of DAG, thereby modulating protein kinase C (PKC) and G-protein signalling.

Resveratrol and small artery compliance and remodeling in the spontaneously hypertensive rat.

Background: Small arteries from the spontaneously hypertensive rat (SHR) exhibit abnormal stiffness and geometry. This study investigated the effects of resveratrol, a polyphenol found in foods such as red grapes, on small arteries in SHR.

Methods: Wistar-Kyoto (WKY) rats and SHR were treated with resveratrol (2.

Astrocytic poly(ADP-ribose) polymerase-1 activation leads to bioenergetic depletion and inhibition of glutamate uptake capacity.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a ubiquitous nuclear enzyme involved in genomic stability. Excessive oxidative DNA strand breaks lead to PARP-1-induced depletion of cellular NAD(+), glycolytic rate, ATP levels, and eventual cell death. Glutamate neurotransmission is tightly controlled by ATP-dependent astrocytic glutamate transporters, and thus we hypothesized that astrocytic PARP-1 activation by DNA damage leads to bioenergetic depletion and compromised glutamate uptake.

Functional and immunocytochemical characterization of D-serine transporters in cortical neuron and astrocyte cultures.

D-serine is an endogenous coagonist of N-methyl-D-aspartate (NMDA) receptors that plays an important role in synaptic function, neuronal development, and excitotoxicity. Mechanisms of D-serine transport are important in regulation of extracellular D-serine concentration and therefore of these critical processes. D-serine can be transported with low affinity through the Na(+)-dependent amino acid transporter termed ASCT2, whereas high-affinity D-serine uptake has been reported through the Na(+)-independent transporter termed asc-1.

Cellular distribution of the neutral amino acid transporter subtype ASCT2 in mouse brain.

ASCT2 is an ASC (alanine-, serine-, cysteine-preferring) neutral amino acid exchanger that may regulate CNS function by transporting amino acid substrates including L-serine, L-cysteine, L-glutamine, L-glutamate and D-serine. Despite the potentially important role of ASCT2 in influencing metabolic and signaling functions of these amino acids in brain, there has been little description of its distribution in brain tissue. We employed a commercially available human ASCT2 antibody in immunohistochemistry studies in adult mouse brain and found a wide regional distribution for ASCT2 that was limited to dendrites labeled by anti-microtubule-associated protein-2 in cortex, hippocampus and striatum.

Antipsychotic drugs cause glial cell line-derived neurotrophic factor secretion from C6 glioma cells.

Objective: Atypical antipsychotic drugs have been shown to protect PC12 cells from cell death induced by a variety of stimuli in culture. Recently, it has been postulated that trophic factors, such as brain-derived neurotrophic factor (BDNF), play a role in preventing cell death. It has been shown that antipsychotic drugs attenuate the decrease in rat hippocampal BDNF that results from immobilization-induced stress.