Pre- and Posttranslational Regulation of β-Endorphin Biosynthesis in the CNS: Effects of Chronic Naltrexone Treatment

Abstract: There appear to be two anatomically distinct β-endorphin (βE) pathways in the brain, the major one originating in the arcuate nucleus of the hypothalamus and a smaller one in the area of the nucleus tractus solitarius (NTS) of the caudal medulla. Previous studies have shown that these two proopiomelanocortin (POMC) systems may be differentially regulated by chronic morphine treatment, with arcuate cells down-regulated and NTS cells unaffected. In the present experiments, we examined the effects of chronic opiate antagonist treatment on βE biosynthesis across different CNS regions to assess whether the arcuate POMC system would be regulated in the opposite direction to that seen after opiate agonist treatment and to determine whether different βE-containing areas might be differentially regulated. Male adult rats were administered naltrexone (NTX) by various routes for 8 days (subcutaneous pellets, osmotic minipumps, or repeated intraperitoneal injections). Brain and spinal cord regions were assayed for total βE-ir, different molecular weight immunoreactive β-endorphin (βE-ir) peptides, and POMC mRNA. Chronic NTX treatment, regardless of the route of administration, reduced total βE-ir concentrations by 30–40% in diencephalic areas (the arcuate nucleus, the remaining hypothalamus, and the thalamus) and the midbrain, but had no effect on βE-ir in the NTS or any region of the spinal cord. At the same time, NTX pelleting increased POMC mRNA levels in the arcuate to ～ 140% of control values. These data suggest that arcuate POMC neurons are up-regulated after chronic NTX treatment (whereas NTS and spinal cord systems remain unaffected) and that they appear to be under tonic inhibition by endogenous opioids. Chromatographic analyses demonstrated that, after chronic NTX pelleting, the ratio of full length βE_1–31 to more processed βE-ir peptides (i.e., βE_1–27 and βE_1–26) tended to increase in a dose-dependent manner in diencephalic areas. Because βE_1–31 is the only POMC product that possesses opioid agonist properties, and βE_1–27 has been posited to function as an endogenous anatgonist of βE_1–31, the NTX-induced changes in the relative concentrations of βE_1–31 and βE_1–27/βE_1–26 may represent a novel regulatory mechanism of POMC cells to alter the opioid signal in the synapse.     

The photosensitivity of the malate oxidase system of a pigmented strain and a carotenoidles mutant of Sarcina lutea (Micrococcus luteus)

The effect of white light on the malate oxidase of Sarcina lutea (Micrococcus luteus) membranes has been examined using a carotenoid-containing and a carotenoidless mutant. At least three photosensitive sites have been detected. Two of these are associated with the malate dehydrogenase complex (malate-menaquinone reductase) and are unaffected by membrane carotenoid. A third site which has been detected beyond the dehydrogenase complex, is protected by carotenoid since it can only be demonstrated in carotenoidless systems. A repair mechanism has been found for one of the two sites in the dehydrogenase complex.     

Dynorphin immunocytochemistry in the rat central nervous system

The distribution of dynorphin in the central nervous system was investigated in rats pretreated with relatively high doses (300–400 μg) of colchicine administered intracerebroventricularly. To circumvent the problems of antibody cross-reactivity, antisera were generated against different portions as well as the full dynorphin molecule (i.e., residues 1–13, 7–17, or 1–17). For comparison, antisera to [Leu]enkephalin (residues 1–5) were also utilized. Dynorphin was found to be widely distributed throughout the neuraxis. Immunoreactive neuronal perikarya exist in hypothalamic magnocellular nuclei, periaqueductal gray, scattered reticular formation sites, and other brain stem nuclei, as well as in spinal cord. Additionally, dynorphin-positive fibers or terminals occur in the cerebral cortex, olfactory bulb, nucleus accumbens, caudate-putamen, globus pallidus, hypothalamus, substantia nigra, periaqueductal gray, many brain stem sties, and the spinal cord. In many areas studied, dynorphin and enkephalin appeared to form parallel but probably separate anatomical systems. The results suggest that dynorphin occurs in neuronal systems that are immunocytochemically distinct from those containing other opioid peptides.     

Ataxin1L Is a Regulator of HSC Function Highlighting the Utility of Cross-Tissue Comparisons for Gene Discovery

Hematopoietic stem cells (HSCs) are rare quiescent cells that continuously replenish the cellular components of the peripheral blood. Observing that the ataxia-associated gene Ataxin-1-like (Atxn1L) was highly expressed in HSCs, we examined its role in HSC function through in vitro and in vivo assays. Mice lacking Atxn1L had greater numbers of HSCs that regenerated the blood more quickly than their wild-type counterparts. Molecular analyses indicated Atxn1L null HSCs had gene expression changes that regulate a program consistent with their higher level of proliferation, suggesting that Atxn1L is a novel regulator of HSC quiescence. To determine if additional brain-associated genes were candidates for hematologic regulation, we examined genes encoding proteins from autism- and ataxia-associated protein–protein interaction networks for their representation in hematopoietic cell populations. The interactomes were found to be highly enriched for proteins encoded by genes specifically expressed in HSCs relative to their differentiated progeny. Our data suggest a heretofore unappreciated similarity between regulatory modules in the brain and HSCs, offering a new strategy for novel gene discovery in both systems.     

A high-fat diet rich in corn oil exaggerates the infarct size and memory impairment in rats with cerebral ischemia and is associated with suppressing osteopontin and Akt,and activating GS3Kβ, iNOS,and NF-κB

Journal of Physiology and Biochemistry - The increase in osteopontin (OPN) levels after stroke induces neural protection by activating Akt signaling and inhibiting GS3Kβ, iNOS, and NF-κB....     

Nitric Oxide Mitigates the Salt-Induced Oxidative Damage in Mustard by UpRegulating the Activity of Various Enzymes

Journal of Plant Growth Regulation - The salt stress limits the production of mustard throughout the world and it is one of the major abiotic stresses. Crop productivity is declining due to the...     

Nitric Oxide-Mediated Enhancement in Photosynthetic Efficiency,Ion Uptake and Carbohydrate Metabolism that Boosts Overall Photosynthetic Machinery in Mustard Plants

Journal of Plant Growth Regulation - Nitric oxide (NO) acts as a gaseous diffusible plant growth regulator. It plays an important role in growth and development of plants. Therefore, in present...     

Research and effectiveness of anti-viral drugs against COVID-19; global public intervention to prevent coronavirus and to improve human health

Since the first case report on COVID-19, its transmission took place rapidly across the globe. Currently, it is reported to be spread into a total of 216 countries and territories. The suppression on industrial and gasoline burning activities accompanied after COVID-19 lock down favorably boosted the nature to restore its deteriorated sections such as in air with the improved Air quality index and in water bodies with the natural tone of purity. Increased use of anti-viral drugs along with herbal therapies has been observed at mass scale as global intervention to prevent the disease. The use of personal protective equipment and disinfection strategies for the control of pandemic has dramatically increased the pollution of plastic and medical waste. This article aims to forecast and highlight the evidence-based impact/changes (+ive and -ive) of coronavirus on the environment, global interventions to prevent the disease along with the levels of effectiveness of personal used protective equipment to stop the spread of coronavirus.     

Telmisartan Ameliorates Neurotrophic Support and Oxidative Stress in the Retina of Streptozotocin-Induced Diabetic Rats

Neurodegeneration is an early event in the diabetic retina which may lead to diabetic retinopathy. One of the potential pathways in damaging retinal neurons is the activation of renin angiotensin system including angiotensin II type 1 receptor (AT1R) in the diabetic retina. The purpose of this study was to determine the effect of telmisartan, an AT1R blocker on retinal level of brain derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) and tyrosine hydroxylase (TH), glutathione (GSH) and caspase activity in the diabetic rats. The dysregulated levels of these factors are known to cause neurodegeneration in diabetic retina. Three weeks streptozotocin induced diabetic rats were orally treated or untreated with telmisartan (10 mg/kg/day). After 4 weeks of treatments, the levels of BDNF and GSH were found to be increased systemically in the sera as well as in the retina of diabetic rats compared to untreated rats as measured by enzyme-linked immunosorbent assay and biochemical techniques (p < 0.05). The caspase-3 activity in the telmisartan treated diabetic retina was decreased compared to untreated diabetic rats (p < 0.05). Western blotting experiments showed the expression levels of BDNF, CNTF and TH were increased compared to untreated diabetic rats (p < 0.05). Thus, our findings show a beneficial effect of AT1R blocker telmisartan in efficiently increasing neurotrophic support, endogenous antioxidant GSH content, and decreasing signs of apoptosis in diabetic retina.