Acupuncture Upregulates G Protein Coupled Activity in Samp8 Mice

2017 ◽  
Vol 35 (4) ◽  
pp. 289-296 ◽  
Author(s):  
Benhua Luo ◽  
Lan Zhao ◽  
Xuezhu Zhang ◽  
Bohong Kan ◽  
Yunhe Liu ◽  
...  
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Cognitive Deficits ◽  
Control Group ◽  
Protein Activity ◽  
Western Blots ◽  
Protein Activation ◽  
Activation Rate ◽  
Cellular Signal ◽  
Samp8 Mice

Background Transmembrane and intracellular signal transduction of G protein is closely related to the pathophysiology of Alzheimer's disease (AD). Objective To explore the effects of Sanjiao acupuncture on G protein signal transduction pathways in the pathogenesis of AD. Methods 36 senescence-accelerated (SAM) prone 8 mice were divided into three groups that remained untreated (SAMP8, n=12) or received Sanjiao acupuncture (SAMP8+SA, n=12) or control acupuncture (SAMP8+CA, n=12). An additional control group of SAM resistant 1 mice was included (SAMR1 group, n=12). Morris water maze tests were used to investigate learning and memory abilities. Immunoprecipitation and Western blotting were used to study expression of G protein subunits and their activities in the cortex/hippocampus. Results Behavioural analysis showed that acupuncture attenuated the severe cognitive deficits observed in untreated/CA-treated SAMP8 mice. The findings of the G protein activation assays via immunoprecipitation and Western blots were that the physiologically coupled activation rate (PCAR) and maximal coupled activation rate (MCAR) of Gαs and Gαi were decreased in the cortex of SAMP8 vs SAMR1 mice. Sanjiao acupuncture induced an upregulation in the PCAR of Gαs and Gαi. In the hippocampus of untreated SAMP8 mice, the PCAR of Gαs and MCAR of both Gαs and Gαi declined, and Sanjiao acupuncture was associated with an upregulation in the MCAR of Gαs and Gαi. There were no significant differences in Gαs and Gαi expression between the groups. Conclusions Sanjiao acupuncture attenuates cognitive deficits in a mouse model of AD via upregulation of G protein activity and stabilisation of the cellular signal.

scholarly journals Label-Free Investigations on the G Protein Dependent Signaling Pathways of Histamine Receptors

2021 ◽  
Vol 22 (18) ◽  
pp. 9739 ◽  
Author(s):  
Ulla Seibel-Ehlert ◽  
Nicole Plank ◽  
Asuka Inoue ◽  
Guenther Bernhardt ◽  
Andrea Strasser
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Drug Targets ◽  
Physiological Role ◽  
Histamine Receptors ◽  
Label Free ◽  
Knock Out ◽  
Protein Activation ◽  
Hek Cells ◽  
Molecular Events

G protein activation represents an early key event in the complex GPCR signal transduction process and is usually studied by label-dependent methods targeting specific molecular events. However, the constrained environment of such “invasive” techniques could interfere with biological processes. Although histamine receptors (HRs) represent (evolving) drug targets, their signal transduction is not fully understood. To address this issue, we established a non-invasive dynamic mass redistribution (DMR) assay for the human H1–4Rs expressed in HEK cells, showing excellent signal-to-background ratios above 100 for histamine (HIS) and higher than 24 for inverse agonists with pEC50 values consistent with literature. Taking advantage of the integrative nature of the DMR assay, the involvement of endogenous Gαq/11, Gαs, Gα12/13 and Gβγ proteins was explored, pursuing a two-pronged approach, namely that of classical pharmacology (G protein modulators) and that of molecular biology (Gα knock-out HEK cells). We showed that signal transduction of hH1–4Rs occurred mainly, but not exclusively, via their canonical Gα proteins. For example, in addition to Gαi/o, the Gαq/11 protein was proven to contribute to the DMR response of hH3,4Rs. Moreover, the Gα12/13 was identified to be involved in the hH2R mediated signaling pathway. These results are considered as a basis for future investigations on the (patho)physiological role and the pharmacological potential of H1–4Rs.

Acupuncture Improves Cognitive Deficits and Increases Neuron Density of the Hippocampus in Middle-Aged Samp8 Mice

2012 ◽  
Vol 30 (4) ◽  
pp. 339-345 ◽  
Author(s):  
Guomin Li ◽  
Xuezhu Zhang ◽  
Haiyan Cheng ◽  
Xuemei Shang ◽  
Hui Xie ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Morris Water Maze ◽  
Cognitive Deficits ◽  
Water Maze ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Neuron Loss ◽  
Neuron Density ◽  
Maze Test ◽  
Samp8 Mice

Objectives To examine whether acupuncture could improve cognitive deficits and reduce the loss of neurons in mice models of ageing. Methods Male 7.5-month-old senescence-accelerated mouse prone 8 (SAMP8) and age-matched senescence-resistant inbred strains 1 (SAMR1) were divided into four groups (n=15 per group): SAMP8 acupuncture group (Pa), SAMP8 non-acupuncture point control group (Pn), SAMP8 control group (Pc) and SAMR1 normal control group (Rc). The behaviours were examined by the Morris water maze test and the neuron density in the hippocampus was estimated by the optical fractionator technique. Results The Morris water maze test demonstrated that the cognitive deficits of SAMP8 mice were improved by acupuncture treatment. Neuronal loss was found in hippocampal regions CA1 (−24%), CA3 (−18%) and DG (−28%) of Pc compared with Rc. The neuron number in hippocampal CA3 and DG of the Pa group was significantly increased by therapeutic acupuncture compared with the Pc group. Conclusions Acupuncture improved the cognitive impairment of middle-aged SAMP8 mice which could be attributed to the reduced neuron loss in hippocampal regions CA3 and DG. These results suggest that reducing neuron loss in the hippocampus by acupuncture is a potential therapeutic approach for the treatment of Alzheimer's disease and cognitive impairment diseases.

Receptor component protein (RCP): a member of a multi-protein complex required for G-protein-coupled signal transduction

2002 ◽  
Vol 30 (4) ◽  
pp. 460-464 ◽  
Author(s):  
M. A. Prado ◽  
B. Evans-Bain ◽  
I. M. Dickerson
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Signal Transduction Pathway ◽  
Cgrp Receptor ◽  
Receptor Component ◽  
Calcitonin Gene ◽  
Cellular Signal ◽  
Cellular Signal Transduction Pathway ◽  
G Protein Coupled ◽  
Component Protein

The calcitonin-gene-related peptide (CGRP) receptor component protein (RCP) is a 148-amino-acid intracellular protein that is required for G-protein-coupled signal transduction at receptors for the neuropeptide CGRP. RCP works in conjunction with two other proteins to constitute a functional CGRP receptor: calcitonin-receptor-like receptor (CRLR) and receptor-activity-modifying protein 1 (RAMP1).CRLR has the stereotypical seven-transmembrane topology of a G-protein-coupled receptor; it requires RAMP1 for trafficking to the cell surface and for ligand specificity, and requires RCP for coupling to the cellular signal transduction pathway. We have made cell lines that expressed an antisense construct of RCP and determined that CGRP-mediated signal transduction was reduced, while CGRP binding was unaffected. Furthermore, signalling at two other endogenous G-protein-coupled receptors was unaffected, suggesting that RCP was specific for a limited subset of receptors.

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