Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcription of the alpha 2-macroglobulin gene (alpha 2M) in rat hepatocytes is strongly induced during acute inflammations by interleukin 6 (IL6). An IL6-response region has previously been mapped in the promoter upstream sequence of this gene. The region consists of two adjacent elements (IL6-REs), the IL6-RE core (CTGGGAA, -164 to -158 bp) and the core homology (CTGGAAA, -184 to -178 bp), elements, that are located 20 bp apart. Both elements bind nuclear factors with very similar protein-DNA contact patterns when they are contained in their original sequence context. A protein-DNA complex III was obtained in gel mobility shift experiments using a probe individually representing the core site. With probes containing both the core and core homology sites, a hormone inducible complex II of slower mobility was obtained. Complex II consisted of multiple copies of the same protein or proteins with very similar molecular masses bound at both sites. The core homology site was the weaker binding site. With a probe containing two tandem copies of the core site, binding at the second site occurred with 81 times greater affinity when the first site was occupied, than when it was free. Thus, the factor binding at the IL6-REs, the IL6-RE binding protein (IL6 RE-BP), was capable of co-operatively interacting with itself. Another factor, IL6-DBP/LAP, has recently been shown to be involved in the regulation of a major subgroup of acute phase genes by IL6. Using recombinant IL6-DBP/LAP and corresponding antisera, we demonstrated here that the IL6 RE-BP of the alpha 2M gene was distinct from IL6-DBP/LAP and from the related factor DBP. Thus, two major IL6-response elements can be distinguished: type 1 elements occurring in the human C-reactive protein, hemopexin and haptoglobin genes and utilizing IL6-DBP/LAP; and type 2 elements occurring in the rat alpha 2M, and alpha 1-acid glycoprotein genes, and utilizing a different IL6 RE-BP. The IL6 RE-BP of the alpha 2M gene was also shown to be distinct from the transcription factor NF kappa B. The IL6RE-BP had relative molecular mass of Mr = 46,000, distinct from IL6-DBP/LAP (Mr = 32,000) and NF kappa B (Mr = 50,000) and its overall DNA binding capacity was induced under acute phase conditions.
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PMID:Interleukin 6 response factor binds co-operatively at two adjacent sites in the promoter upstream region of the rat alpha 2-macroglobulin gene. 172 49

To assess the chondroprotective effect and influence of N,N'-bis(1,5-dimethyl-2-phenyl-1,2-dihydro-3-oxopyrazol-4-yl) sebacamide (dpdo) that was synthesized through the reaction of phenazone with sebacoyl chloride and screened for its biological activity especially as anti-arthritic and anti-inflammatory agent in a monoiodoacetate (MA)-induced experimental osteoarthritis (OA) model. Thirty male albino rats weighing "190-200 g" were divided randomly into three groups (10 each): control, MA-induced OA, and MA-induced OA + dpdo. In MA-induced OA rat, the tumor necrosis factor alpha, interleukin 6, C-reactive protein, rheumatoid factors, reactive oxygen species, as well as all the mitochondrial markers such as mitochondria membrane potential, swelling mitochondria, cytochrome c oxidase (complex IV), and serum oxidative/antioxidant status (malondialdehyde level and activities of myeloperoxidase and xanthine oxidase) are elevated. Also, the activity of succinate dehydrogenase (complex II), levels of ATP, the level of glutathione (GSH), and thiol were markedly diminished in the MA-induced OA group compared to the normal control rats. These findings showed that mitochondrial function is associated with OA pathophysiological alterations and high gene expressions of (IL-6, TNF-a, and IL-1b) and suggests a promising use of dpdo as potential ameliorative agents in the animal model of OA and could act as anti-inflammatory agent in case of severe infection with COVID-19. It is clearly appeared in improving the bone cortex and bone marrow in the treated group with the novel compound in histological and transmission electron microscopic sections which is a very important issue today in fighting severe infections that have significant effects on the blood indices and declining of blood corpuscles like COVID-19, in addition to declining the genotoxicity and inflammation induced by MA in male rats. The novel synthesized compound was highly effective in improving all the above mentioned parameters.
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PMID:Synthesis of N,N'-bis(1,5-dimethyl-2-phenyl-1,2-dihydro-3-oxopyrazol-4-yl) sebacamide that ameliorate osteoarthritis symptoms and improve bone marrow matrix structure and cartilage alterations induced by monoiodoacetate in the rat model: "Suggested potent anti-inflammatory agent against COVID-19". 3284 Mar 87