Combining NO release W/ anti-inflammatory activity preserves nigrostriatal dopaminergic innervation and prevents motor impairment in a MPTP model of Parkinson's disease

Combining nitric oxide release with anti-inflammatory activity preserves nigrostriatal dopaminergic innervation and prevents motor impairment in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease

Essential role of ER-alpha-dependent NO production... [Am J Physiol Heart Circ Physiol. 2010] - PubMed result

Well....well!  More evidence of sexual dimorphism.....????


Essential role of ER-alpha-dependent NO production... [Am J Physiol Heart Circ Physiol. 2010] - PubMed result: "These data thus suggest that RESV inhibits vascular proliferative responses after injury, predominately through an ER-alpha-dependent increase in NO production."

Gut Inflammation and Changes in Intestinal Function From Loss of NO Neurons~!

In a recent study the author writes "enteric neurons are supported by glial cells, the ENS counterparts of astrocytes of the CNS, that can modulate enteric neuron function. Enteric neurons are known to control virtually all GI functions, including motility, secretion, blood flow, mucosal growth and aspects of the local immune system. Consequently, permanent or even transient structural alterations in the ENS, as occur in IBD, disrupt normal GI function. Structural changes in the ENS are predictive of disease evolution suggesting that neuroprotection would decrease disease severity and may play a role in recurrence in CD." Further he continues that under conditions of experimental trichinosis infection in the murine "that in this animal model of colitis, there was a significant loss of nitric oxide synthase- (NOS-) immunoreactive neurons in the myenteric plexus of infected rats. Moreover, the selective loss of NOS-positive neurons appears to underlie changes in motility." (Lakhan) Recent reports also suggest that hormones such as serotonin influences gut regulation and may activate inflammatory cytokines in the intestine leading to alterations in gut function. (Khan) Inflammatory activity such as Tnf-a in the periphery such as the gut may influence production of cytokines and changes in gene expression in the brain that change behavior and have other unexpected health effects.




Khan, W. I. and Ghia, J. E. (2010). Gut hormones: emerging role in immune activation and inflammation. Clinical and experimental immunology, 161(1):19-27.
http://www.citeulike.org/user/HEIRS/article/7323747

Lakhan, S. E. and Kirchgessner, A. (2010). Neuroinflammation in inflammatory bowel disease. Journal of neuroinflammation, 7:37+.
http://www.citeulike.org/user/HEIRS/article/7471133

Ascorbic Acid May Prevent Lead-Induced Hypertension via Nitric Oxide!

"ascorbic acid as an antioxidant prevents the lead induced hypertension. This effect may be mediated by inhibition of NOc oxidation and thereby increasing availability of NO."

Effect of ascorbic acid supplementation on nitric oxide metabolites and systolic blood pressure in rats exposed to lead Mohammad A, Ali N, Reza B, Ali K - Indian J Pharmacol:

Nrf2 Regulation of Lipids and Glucose: Modulation of PGC-1a Through Protein

Over the past several months, I have proposed that certain environmental illnesses such as chemical sensitivity may be due to alterations in metabolic homeostasis from inflammatory processes and may include dysfunction of the antioxidant system Nrf2 and levels of PGC-1a, possibly through alterations in methylation or some other condition. Several recent studies provides a clearer picture of how this may occur in different tissues. PGC-1a is an important protein that participates in a number of processes including glucose and lipid regulation. (Kelly) In other blogs, we have explained how altered levels are apparent in the tissues of diabetes and for this reason, changes occur in metabolic function. As for Nrf2, it mitigates the effect of inflammatory cytokines as well as, upregulates proteins used in downstream processes of PGC-1a.

For several years now, it has been known that PGC-1a plays an important role in mitochondrial biogenesis and regulates cellular energy metabolism in the liver and muscle and is activated by SIRT1. SIRT1 is another protein we have discussed at length and is activated by the compound resveratrol in red wine and grape skins. Last year, one study showed that in neurons overexpression of SIRT1 or suppression of a GCN5 aminotransferase activated PGC-1a and increased mitochondrial density. Because, several experts have postulated that environmental illnesses may be due to mitochondrial dysfunction from exposures and endogenous processes, increasing mitochondrial density may reduce cellular impairment and increase neuronal survival and provide a therapeutic target.

It seems that GCN5 has the capacity to interact with the PGC family in general. Kelly et al recently found that GCN5 interacts with PGC-1b to repress its transcription activites associated with the estrogen receptor and NRF-1. As a result, the induction of GLUT4 and MCAD were reduced in skeletal muscle which translates to a blunted response of insulin-mediated glucose transport and increases the likelihood of the role of both PGC-1a and PGC-1b in metabolic disease.

As far as Nrf2 goes, in the liver the enzyme ATP citrate lyase (ACL)"relates energy balance" to GCN5 through the control of acetyl-CoA. In a new study by Kitteringham, the findings provide evidence that Nrf2 negatively regulates ATP citrate and therefore may provide a more influential role in glucose and lipid regulation than previously thought. (Kitteringham)

Notes:
***NO derived from constitutive nNOS plays a crucial role in the activity pattern of mitochondrial enzymes. In particular, the NO-mediated suppression of citrate synthase activity may be attributed to a regulatory function of NO in fatty acid synthesis. Inhibition of mitochondrial respiration by NO appears to be at least partially compensated for by a respective increase in the activity of respiratory chain complexes. (Schild) One could suggest the actions of Nrf2 may assist in the regulation of this function.



Kitteringham, N. R., Abdullah, A., Walsh, J., Randle, L., Jenkins, R. E., Sison, R., Goldring, C. E., Powell, H., Sanderson, C., Williams, S., Higgins, L., Yamamoto, M., Hayes, J., and Park, B. K. (2010). Proteomic analysis of nrf2 deficient transgenic mice reveals cellular defence and lipid metabolism as primary nrf2-dependent pathways in the liver. Journal of proteomics, 73(8):1612-1631.
http://www.citeulike.org/user/HEIRS/article/7329576

Jeninga, E. H., Schoonjans, K., and Auwerx, J. (2010). Reversible acetylation of pgc-1: connecting energy sensors and effectors to guarantee metabolic flexibility. Oncogene, aop(current).
http://www.citeulike.org/user/HEIRS/article/7282171

Wareski, P., Vaarmann, A., Choubey, V., Safiulina, D., Liiv, J., Kuum, M., and Kaasik, A. (2009). Pgc-1alpha and pgc-1beta regulate mitochondrial density in neurons. The Journal of biological chemistry, 284(32):21379-21385.
http://www.citeulike.org/user/HEIRS/article/4965303?show_msg=already_posted

Kelly, T. J., Lerin, C., Haas, W., Gygi, S. P., and Puigserver, P. (2009). Gcn5-mediated transcriptional control of the metabolic coactivator pgc-1beta through lysine acetylation. The Journal of biological chemistry, 284(30):19945-19952.
http://www.citeulike.org/user/HEIRS/article/5199678?show_msg=already_posted

Schild, L., Jaroscakova, I., Lendeckel, U., Wolf, G., and Keilhoff, G. (2006). Neuronal nitric oxide synthase controls enzyme activity pattern of mitochondria and lipid metabolism. FASEB J., 20(1):145-147.
http://www.citeulike.org/user/HEIRS/article/7329782

Effect of CRH on NO bioavailability, ROS production and antioxidant defense systems in endothelial EAhy926 cells.

The data indicate that CRH may act as a regulator of pro-inflammatory mechanisms inducing adaptation of endothelial cell function to local stress.

"Gougoura, S., Liakos, P., and Koukoulis, G. N. (2010). Effect of crh on no bioavailability, ros production and antioxidant defense systems in endothelial eahy926 cells. Free radical research, 44(7):803-812."
CiteULike: Effect of CRH on NO bioavailability, ROS production and antioxidant defense systems in endothelial EAhy926 cells.:

Renal protection by a soy diet associated with restoration of NO generation.

"renal protective effect of soy protein appears to be mediated by improvement of NO generation and pointed out to caveolin-1 overexpression as a potential pathophysiological mechanism in renal disease"
CiteULike: Renal protection by a soy diet in obese Zucker rats is associated with restoration of nitric oxide generation.:

Nitric Oxide Metabolite Production During Exercise in Chronic Fatigue Syndrome: A Case-Control Study"

Mary Ann Liebert, Inc. - Journal of Women's Health - 0(0):: "Nitric Oxide Metabolite Production During Exercise in Chronic Fatigue Syndrome: A Case-Control Study"

Septic shock: Nitric oxide beneficial after all

Septic shock: Nitric oxide beneficial after all: "URL: Septic shock: Nitric oxide beneficial after all

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Prevention of atherosclerosis by interference with the vascular nitric oxide system.

Prevention of atherosclerosis by interference with the vascular nitric oxide system.