Damaged or unwanted cellular proteins are degraded by either autophagy or the ubiquitin/proteasome pathway. In Arabidopsis thaliana, sensing of D-glucose is achieved by the heterotrimeric G protein complex and regulator of G-protein signaling 1 (AtRGS1). Here, we showed that starvation increases proteasome-independent AtRGS1 degradation, and it is correlated with increased autophagic flux. RGS1 promoted the production of autophagosomes and autophagic flux; RGS1-yellow fluorescent protein (YFP) was surrounded by vacuolar dye FM4-64 (red fluorescence). RGS1 and autophagosomes co-localized in the root cells of Arabidopsis and BY-2 cells. We demonstrated that the autophagosome marker ATG8a interacts with AtRGS1 and its shorter form with truncation of the seven transmembrane and RGS1 domains in planta. Altogether, our data indicated the correlation of autophagosome formation with degradation and endocytosis of AtRGS1 through ATG8a.
Dahl salt-sensitive (Dahl S) rats are prone to salt-dependent hypertension with severe organ damage, including stroke, cardiac failure and renal insufficiency. The mechanism for this susceptibility to kidney injury has not been elucidated. The present study proposed that an upregulation of intracellular signaling of angiotensin II (Ang-II) is responsible for the susceptibility to hypertensive kidney injury in Dahl S rats. Spontaneously hypertensive rats exhibited higher systolic blood pressure (SBP) and lower kidney damage than Dahl S rats fed a high-salt diet for 2 weeks. Ang-II infusion for 4 weeks significantly increased SBP in Dahl S and Dahl salt-resistant (Dahl R) rats fed a low-salt diet. The increase in SBP in Dahl S rats was associated with significant kidney injury with greater glomerular sclerosis (P<0.001). The expression of regulatory protein of Gαq signaling-2 (RGS2) mRNA in the aortic walls in response to Ang-II infusion was lower in Dahl S than Dahl R rats (P<0.05). Ang-II significantly increased RGS2 mRNA in the aorta in Dahl R rats, but the response was apparently blunted in Dahl S rats. These results suggest that Dahl S rats exhibit a blunted RGS2 response to Ang-II, and this blunted response may be partially responsible for the susceptibility to renal injury in Dahl S rats.
- MeSH
- angiotensin II farmakologie MeSH
- hypertenze komplikace metabolismus patofyziologie MeSH
- krevní tlak účinky léků fyziologie MeSH
- krysa rodu rattus MeSH
- ledviny účinky léků metabolismus patofyziologie MeSH
- nemoci ledvin etiologie metabolismus patofyziologie MeSH
- potkani inbrední Dahl MeSH
- proteiny RGS genetika metabolismus MeSH
- sodík dietní MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Alzheimer's disease (AD) is the most frequent cause of dementia. Misfolded protein pathological hallmarks of AD are brain deposits of amyloid-β (Aβ) plaques and phosphorylated tau neurofibrillary tangles. However, doubts about the role of Aβ in AD pathology have been raised as Aβ is a common component of extracellular brain deposits found, also by in vivo imaging, in non-demented aged individuals. It has been suggested that some individuals are more prone to Aβ neurotoxicity and hence more likely to develop AD when aging brains start accumulating Aβ plaques. Here, we applied genome-wide transcriptomic profiling of lymphoblastoid cells lines (LCLs) from healthy individuals and AD patients for identifying genes that predict sensitivity to Aβ. Real-time PCR validation identified 3.78-fold lower expression of RGS2 (regulator of G-protein signaling 2; P=0.0085) in LCLs from healthy individuals exhibiting high vs low Aβ sensitivity. Furthermore, RGS2 showed 3.3-fold lower expression (P=0.0008) in AD LCLs compared with controls. Notably, RGS2 expression in AD LCLs correlated with the patients' cognitive function. Lower RGS2 expression levels were also discovered in published expression data sets from postmortem AD brain tissues as well as in mild cognitive impairment and AD blood samples compared with controls. In conclusion, Aβ sensitivity phenotyping followed by transcriptomic profiling and published patient data mining identified reduced peripheral and brain expression levels of RGS2, a key regulator of G-protein-coupled receptor signaling and neuronal plasticity. RGS2 is suggested as a novel AD biomarker (alongside other genes) toward early AD detection and future disease modifying therapeutics.
- MeSH
- Alzheimerova nemoc diagnóza genetika patologie MeSH
- amyloidní beta-protein genetika MeSH
- amyloidní plaky genetika patologie MeSH
- buněčné linie MeSH
- časná diagnóza MeSH
- celogenomová asociační studie * MeSH
- data mining * MeSH
- exprese genu genetika MeSH
- fenotyp MeSH
- genetické asociační studie MeSH
- genetické markery genetika MeSH
- lidé MeSH
- mozek patologie MeSH
- neurofibrilární klubka genetika patologie MeSH
- proteiny RGS genetika MeSH
- senioři MeSH
- stanovení celkové genové exprese * MeSH
- výpočetní biologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: The regulator of G-protein signaling (RGS) molecules represent a class of proteins that modulate the signaling activity of G-protein coupled receptors. Regulator of G-protein signaling 4 (RGS4) is of particular interest in schizophrenia due to reported downregulation of RGS4 transcripts in schizophrenia as well as a connection between RGS4 and a number of receptors implicated in schizophrenia. The mechanism of RGS4 involvement in the pathophysiology of this illness is not clear. METHODS: To elucidate thise role of RGS4 in pathophysiology of schizophrenia, we silenced RGS4 using siRNAs in human neuroblastoma cell lines and we studied the effects of differential RGS4 expression by microarray. RESULTS AND CONCLUSION: The cell lines with downregulated expression of RGS4 showed 67 genes with changed expression (30 underexpressed and 37 overexpressed). We have detected three subgroups of genes which might be implicated in schizophrenia pathophysiology: histone genes, which suggest epigenetic mechanisms of the disease; genes for transcription factors associated with other genes relevant to schizophrenia pathology (BDNF and DISCI1) and a heterogeneous group containing genes for G-proteins (GPR50 and GPR64) and calcium binding proteins.
- MeSH
- buněčné linie MeSH
- down regulace MeSH
- genetická transkripce MeSH
- genom lidský genetika MeSH
- histony genetika MeSH
- kultivované buňky MeSH
- lidé MeSH
- malá interferující RNA farmakologie MeSH
- mikročipová analýza MeSH
- mozkový neurotrofický faktor genetika MeSH
- neurony účinky léků metabolismus MeSH
- proteiny nervové tkáně genetika MeSH
- proteiny RGS genetika MeSH
- receptory spřažené s G-proteiny genetika MeSH
- schizofrenie genetika MeSH
- stanovení celkové genové exprese MeSH
- umlčování genů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
