scholarly journals Metabolic Activation and Covalent Protein Binding of Berberrubine: Insight into the Underlying Mechanism Related to Its Hepatotoxicity

2020 ◽  
Vol Volume 14 ◽  
pp. 4423-4438
Author(s):  
Kai Wang ◽  
Jinqiu Rao ◽  
Tingting Zhang ◽  
Qing Gao ◽  
Jichao Zhang ◽  
...  
Keyword(s):  
Protein Binding ◽  
Metabolic Activation ◽  
Underlying Mechanism ◽  
Covalent Protein Binding ◽  
Insight Into

scholarly journals Mechanism of riboregulation of p62 protein oligomerisation by vault RNA1-1 in selective autophagy

2021 ◽  
Author(s):  
Magdalena Buescher ◽  
Rastislav Horos ◽  
Kevin Haubrich ◽  
Nikolay Dobrev ◽  
Florence Baudin ◽  
...  
Keyword(s):  
Chemical Structure ◽  
Membrane Vesicles ◽  
Underlying Mechanism ◽  
Selective Autophagy ◽  
Ubiquitinated Proteins ◽  
Flexible Loop ◽  
Structure Probing ◽  
Molecular Determinants ◽  
Necessary And Sufficient ◽  
Insight Into

Macroautophagy ensures the clearance of intracellular substrates ranging from single ubiquitinated proteins to large proteotoxic aggregates and defective organelles. The selective autophagy receptor p62 binds these targets and recruits them to double-membrane vesicles, which fuse with lysosomes to degrade their content. We recently uncovered that p62 function is riboregulated by the small non-coding vault RNA1-1. Here, we present detailed insight into the underlying mechanism. We show that the PB1 domain and adjacent linker region of p62 (aa 1-122) are necessary and sufficient for specific vault RNA1-1 binding, and identify lysine 7 and arginine 21 as key hinges for p62 riboregulation. Chemical structure probing of vault RNA1-1 further reveals a central flexible loop within the RNA that mediates the specific p62 interaction. Our data define molecular determinants that govern mammalian autophagy via the p62-vault RNA1-1 riboregulatory pair.

Direct insight into the formation driving force, sensitivity and detonation performance of the observed CL-20-based energetic cocrystals

CrystEngComm ◽  
2018 ◽  
Vol 20 (38) ◽  
pp. 5790-5800 ◽  
Author(s):  
Binghui Duan ◽  
Yuanjie Shu ◽  
Ning Liu ◽  
Bozhou Wang ◽  
Xianming Lu ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Driving Force ◽  
Underlying Mechanism ◽  
Detonation Performance ◽  
Force Sensitivity ◽  
Insight Into ◽  
Formation Driving

This work elucidated the underlying mechanism of the dramatic and divergent physicochemical properties of CL-20-based energetic cocrystals.

Role of metabolism in K-induced tension changes in guinea pig taenia coli

1965 ◽  
Vol 208 (6) ◽  
pp. 1203-1205 ◽  
Author(s):  
M. Pfaffman ◽  
N. Urakawa ◽  
W. C. Holland
Keyword(s):  
Guinea Pig ◽  
Active Transport ◽  
Underlying Mechanism ◽  
Taenia Coli ◽  
Na Transport ◽  
Phasic Response ◽  
Metabolic Intermediates ◽  
Substrate Removal ◽  
Insight Into

Further insight into the underlying mechanism(s) of the K-induced phasic and tonic contractions of the taenia coli of the guinea pig was obtained by examining the effects of various metabolic intermediates, inhibitors of metabolism and active transport, on these responses. Evidence is presented to support the thesis that the tonic response is dependent on the aerobic breakdown of carbohydrates and is abolished by substrate removal, a decrease of temperature, DNP, lithium, and ouabain. These same factors have little or no effect on the phasic response. From the evidence presented, it is concluded that the phasic response is a passive process, whereas the tonic contracture is an active one depending on metabolism and possibly linked to active Na transport.

Structural Insight Into Protein Binding of Boron Tracedrug UTX-97 Revealed by the Co-Crystal Structure With Lysozyme at 1.26 Å Resolution

2016 ◽  
Vol 105 (8) ◽  
pp. 2298-2301
Author(s):  
Yukio Morimoto ◽  
Hideko Nagasawa ◽  
Yoshihiro Uto ◽  
Toshiyuki Chatake ◽  
Hitoshi Hori
Keyword(s):  
Crystal Structure ◽  
Protein Binding ◽  
Structural Insight ◽  
Insight Into

scholarly journals Increased Mitochondrial Dysfunction Associated with Autophagy and Mitophagy in Cerebrospinal Fluid Cells Following Subarachnoid Hemorrhage in Patients with Delayed Cerebral Ischemia

2021 ◽  
Author(s):  
Dong Hyuk Youn ◽  
Youngmi Kim ◽  
Bong Jun Kim ◽  
Myeong Seon Jeong ◽  
Jooeun Lee ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Mitochondrial Dysfunction ◽  
Delayed Cerebral Ischemia ◽  
Underlying Mechanism ◽  
Autophagic Flux ◽  
Immunogold Staining ◽  
Csf Cells ◽  
Insight Into

Abstract Decreased mitochondrial membrane potential in cerebrospinal fluid (CSF) was observed in patients with subarachnoid hemorrhage (SAH) accompanied with delayed cerebral ischemia (DCI); however, the underlying mechanism remains unclear. We evaluated the mitochondrial dysfunction associated with autophagy and mitophagy in CSF cells for possible insight into DCI pathogenesis. CSF samples were collected from 56 SAH patients (DCI, n=21; and non-DCI, n=35). We analyzed CSF cells using autophagy and mitophagy markers (DAPK1, BNIP3L, BAX, PINK1, ULK1, and NDP52) via qRT-PCR and western blotting of proteins (BECN1, LC3, and p62). Confocal microscopy and immunogold staining were performed to demonstrate the differentially expression of markers within dysfunctional mitochondria. Significant induction of autophagic flux with accumulation of autophagic vacuoles, increased expression of BECN1, LC3-II, and p62 degradation were observed during DCI. DCI patients showed a significantly increased mRNA expression (2-ΔCt) than non-DCI patients: DAPK1, 0.279 (0.220–0.297) in DCI vs. 0.043 (0.021–0.086) in non-DCI; BNIP3L, 0.134 (0.060–0.202) in DCI vs. 0.045 (0.020–0.101) in non-DCI; and PINK1, 0.064 (0.044–0.810) in DCI vs. 0.045 (0.012–0.063) in non-DCI. Other markers including BAX, ULK1, and NDP52 did not differ significantly. The vWF-positive CSF cells showed a colocalization with antibodies for DAPK1, BNIP3L/NIX, PINK1, and BECN1 with dysfunctional mitochondria. Increased dysfunctional mitochondria associated with autophagy and mitophagy are closely associated with DCI pathogenesis.

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