Necroptosis is a programmed necrosis that is mediated by receptor-interacting protein kinases RIPK1, RIPK3 and the mixed lineage kinase domain-like protein, MLKL. Necroptosis must be strictly regulated to maintain normal tissue homeostasis, and dysregulation of necroptosis leads to the development of various inflammatory, infectious, and degenerative diseases. Ubiquitylation is a widespread post-translational modification that is essential for balancing numerous physiological processes. Over the past decade, considerable progress has been made in the understanding of the role of ubiquitylation in regulating necroptosis. Here, we will discuss the regulatory functions of ubiquitylation in necroptosis signaling pathway. An enhanced understanding of the ubiquitylation enzymes and regulatory proteins in necroptotic signaling pathway will be exploited for the development of new therapeutic strategies for necroptosis-related diseases.
Two melanocyte-stimulating hormone release inhibiting factor-1 (MIF-1) also known as L-prolyl-L-leucyl-glycinamide (PLG) peptidomimetic analogs, 3(R)-[[[2(S)-pyrrolidinyl]carbonyl]-amino]-3-(butyl)-2-oxo-1-pyrrolidineacetamide trifluoroacetate (A) and 3(R)-[[[2(S)-pyrrolidinyl]carbonyl]amino]-3-(benzyl)-2-oxo-1-pyrrolidineacetamide trifluoroacetate (B), were evaluated for their ability to modulate dopaminergic activity by measuring apomorphine-induced rotations in 6-hydroxydopamine (6-OHDA)-lesioned rats, and haloperidol (HP)-induced vacuous chewing movements (VCMs) in rats; animal models of Parkinson's disease (PD) and human tardive dyskinesia (TD), respectively. In the 6-OHDA model, both analogs were found to potentiate the contralateral rotational behavior induced by apomorphine dose-dependently and with approximately the same potency. Furthermore, each analog was able to significantly attenuate HP-induced VCMs with almost equal efficacy. The potency and efficacy of these analogs were significantly greater than their parent compound, PLG. These results suggest that both analogs can modulate dopaminergic activity in vivo, likely by the same mechanisms recruited by PLG previously reported. 相似文献
A novel pink-coloured, non-spore-forming, non-motile, Gram-negative bacterium, designated YIM 48858T, is described by using a polyphasic approach. The strain can grow at pH 6.5–9 (optimum at pH 7) and 25–30°C (optimum at 28°C).
NaCl is not required for its growth. Positive for oxidase and catalase. Urease activity, nitrate reduction, starch and Tween
80 tests are negative reaction. 16S rRNA gene sequence similarity studies showed that strain YIM 48858T is a member of the genus Rubellimicrobium, with similarities of 96.3, 95.7 and 95.5% to Rubellimicrobium mesophilum MSL-20T, Rubellimicrobium aerolatum 5715S-9T and Rubellimicrobiumthermophilum DSM 16684T, respectively. Q-10 was the predominant respiratory ubiquinone as in the other members of the genus Rubellimicrobium. The major polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphoglycolipid, glycolipid and the major fatty
acids were C18:1 ω7c, C16:0 and C10:0 3-OH, which are very different from the valid published species. The DNA G + C content
was 67.7 mol%. Both phylogenetic and chemotaxonomic evidence supports that YIM 48858T is a novel species of the genus Rubellimicrobium, for which the name Rubellimicrobium roseum sp. nov. is proposed. The type strain is YIM 48858T (=CCTCC AA 208029T =KCTC 23202T). 相似文献