Histochemical and immunoelectron microscopic analysis of ganglioside GM3 in human kidney

Kaneko, Tetsuya; Tsubakihara, Yoshiharu; Fushimi, Hiroaki; Yamaguchi, Seiji; Takabatake, Yoshitsugu; Rakugi, Hiromi; Kawakami, Hayato; Isaka, Yoshitaka

doi:10.1007/s10157-014-1003-0

Cited by 12 publications

(12 citation statements)

References 35 publications

(45 reference statements)

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“…Immunohistochemical and electron microscopy analyses of human kidney specimens have confirmed the specific presence of GM3 in the foot processes of podocytes [28], comforting the functional data described in the previous paragraph [6]. This confirms the high abundance of this type of ganglioside in podocytes, and its participation in maintaining the functional integrity of the filtration barrier.…”

Section: Gm3 and Gd3supporting

confidence: 84%

Gangliosides in Podocyte Biology and Disease

Savas

Astarita

Aureli

et al. 2020

IJMS

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Gangliosides constitute a subgroup of glycosphingolipids characterized by the presence of sialic acid residues in their structure. As constituents of cellular membranes, in particular of raft microdomains, they exert multiple functions, some of them capital in cell homeostasis. Their presence in cells is tightly regulated by a balanced expression and function of the enzymes responsible for their biosynthesis, ganglioside synthases, and their degradation, glycosidases. The dysregulation of their abundance results in rare and common diseases. In this review, we make a point on the relevance of gangliosides and some of their metabolic precursors, such as ceramides, in the function of podocytes, the main cellular component of the glomerular filtration barrier, as well as their implications in podocytopathies. The results presented in this review suggest the pertinence of clinical lipidomic studies targeting these metabolites.

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Section: Gm3 and Gd3supporting

confidence: 84%

Gangliosides in Podocyte Biology and Disease

Savas

Astarita

Aureli

et al. 2020

IJMS

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“…Immunohistochemical analyses indicated that ganglioside GM3 was distributed in renal proximal tubules and glomeruli. Immunoelectron microscopy showed that ganglioside GM3 was localized in Golgi region of renal proximal tubule cells and the foot process of podocyte [65]. Ganglioside GM3 might take a part of the negative electric charge on the podocyte surface and multiple bioactivities of ganglioside GM3 played important roles for maintaining glomerular physiological function.…”

Section: Tablementioning

confidence: 99%

Activated NF-κB/Nrf2 and Wnt/β-catenin pathways are associated with lipid metabolism in CKD patients with microalbuminuria and macroalbuminuria

Feng

Chen

et al. 2019

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Early diagnosis of CKD patients at risk for microalbuminuria or macroalbuminuria could facilitate clinical outcomes and long-term survival. Considering the few and limited efficacy of current biomarkers in early detection, we aim to discover plasma lipids that effectively predict the development of CKD paitents with microalbuminuria or macroalbuminuria. A total of 380 healthy controls and 1156 patients with CKD stages 3 to 5 were stratified by urine albumin-creatinine ratio as microalbuminuria (30-300 mg/g) and macroalbuminuria (> 300 mg/g). Fasting plasma samples were determined by UPLC-HDMS based on lipidomics. Quantitative realtime polymerase chain reaction, Western blot and immunohistochemical analyses were used to validate the lipid metabolism-associated pathways. Pathway analysis demonstrated that these lipids were closely associated with PPARγ, inflammatory mediator regulation of TRP channels and RAS signaling, which were intimately involved in activated NF-κB and Nrf2 pathways. We further carried out pathway validation and demonstrated that NF-κB pathway was activated in patients with macroalbuminuria compared with CKD patients with microalbuminuria, while Nrf2-associated protein expression was downregulated, which was accompanied by the up-regulation of Wnt/β-catenin signaling pathway. Four lipids including DTA, 5,8-TDA, GGD3 and DHA that showed great potential in the discrimination of CKD patients with microalbuminuria and healthy controls were selected by logistic regression analysis. Additionally, six lipid species including CDCA, glucosylceramide, GGD2, TTA, DHA and EDA that contributed to the discrimination of CKD patients with microalbuminuria and macroalbuminuria were selected by logistic LASSO regression Gangliosides were first identified and might be promising therapeutic targets for CKD patients with the different degree of albuminuria. Collectively, this study first demonstrates the

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“…Kidney and gastric luminal epithelia, constantly exposed to low pH, are enriched in GM3 glycosphingolipid at their apical membranes [ 33 , 34 , 35 ]. Therefore, we wondered whether astrocytes in an acidified microenvironment (such as that encountered during ischaemia or cancer) could utilise GM3 as a major surface pH sensor due to its conformational receptivity and susceptibility to protonation via its sialic acid containing headgroup.…”

Section: Resultsmentioning

confidence: 99%

Neurotherapeutic implications of sense and respond strategies generated by astrocytes and astrocytic tumours to combat pH mechanical stress

K.G

Krishna

Mishra

2021

Neuropathology Appl Neurobio

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Aims Astrocytes adapt to acute acid stress. Intriguingly, cancer cells with astrocytic differentiation thrive even better in an acidic microenvironment. How changes in extracellular pH (pHe) are sensed and measured by the cell surface assemblies that first intercept the acid stress, and how this information is relayed downstream for an appropriate survival response remains largely uncharacterized. Methods In vitro cell‐based studies were combined with an in vivo animal model to delineate the machinery involved in pH microenvironment sensing and generation of mechanoadaptive responses in normal and neoplastic astrocytes. The data was further validated on patient samples from acidosis driven ischaemia and astrocytic tumour tissues. Results We demonstrate that low pHe is perceived and interpreted by cells as mechanical stress. GM3 acts as a lipid‐based pH sensor, and in low pHe, its highly protonated state generates plasma membrane deformation stress which activates the IRE1‐sXBP1‐SREBP2‐ACSS2 response axis for cholesterol biosynthesis and surface trafficking. Enhanced surface cholesterol provides mechanical tenacity and prevents acid‐mediated membrane hydrolysis, which would otherwise result in cell leakage and death. Conclusions In summary, activating these lipids or the associated downstream machinery in acidosis‐related neurodegeneration may prevent disease progression, while specifically suppressing this key mechanical ‘sense‐respond’ axis should effectively target astrocytic tumour growth.

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Histochemical and immunoelectron microscopic analysis of ganglioside GM3 in human kidney

Abstract: Ganglioside GM3 might take a part of the negative electric charge on the surface of podocyte and its multiple physiological actions may play pivotal roles for maintaining glomerular function.

Cited by 12 publications

References 35 publications

Gangliosides in Podocyte Biology and Disease

Gangliosides in Podocyte Biology and Disease

Activated NF-κB/Nrf2 and Wnt/β-catenin pathways are associated with lipid metabolism in CKD patients with microalbuminuria and macroalbuminuria

Neurotherapeutic implications of sense and respond strategies generated by astrocytes and astrocytic tumours to combat pH mechanical stress

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