scholarly journals Renal Proximal Tubule Cell Cannabinoid-1 Receptor Regulates Bone Remodeling and Mass via a Kidney-to-Bone Axis

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 414
Author(s):  
Saja Baraghithy ◽  
Yael Soae ◽  
Dekel Assaf ◽  
Liad Hinden ◽  
Shiran Udi ◽  
...  
Keyword(s):  
Bone Mass ◽  
Proximal Tubule ◽  
Bone Remodeling ◽  
Kidney Function ◽  
Bone Cells ◽  
Critical Role ◽  
Renal Proximal Tubule ◽  
Proximal Tubule Cell ◽  
Protective Effects ◽  
Cannabinoid 1 Receptor

The renal proximal tubule cells (RPTCs), well-known for maintaining glucose and mineral homeostasis, play a critical role in the regulation of kidney function and bone remodeling. Deterioration in RPTC function may therefore lead to the development of diabetic kidney disease (DKD) and osteoporosis. Previously, we have shown that the cannabinoid-1 receptor (CB1R) modulates both kidney function as well as bone remodeling and mass via its direct role in RPTCs and bone cells, respectively. Here we employed genetic and pharmacological approaches that target CB1R, and found that its specific nullification in RPTCs preserves bone mass and remodeling both under normo- and hyper-glycemic conditions, and that its chronic blockade prevents the development of diabetes-induced bone loss. These protective effects of negatively targeting CB1R specifically in RPTCs were associated with its ability to modulate erythropoietin (EPO) synthesis, a hormone known to affect bone mass and remodeling. Our findings highlight a novel molecular mechanism by which CB1R in RPTCs remotely regulates skeletal homeostasis via a kidney-to-bone axis that involves EPO.

Formate: A Critical Intermediate for Chloride Transport in the Proximal Tubule

Physiology ◽  
1987 ◽  
Vol 2 (5) ◽  
pp. 160-164
Author(s):  
LP Karniski ◽  
PS Aronson
Keyword(s):  
Formic Acid ◽  
Proximal Tubule ◽  
Cell Membranes ◽  
Chloride Transport ◽  
Critical Role ◽  
Renal Proximal Tubule ◽  
Proximal Tubule Cell ◽  
Tubule Cell ◽  
Active Uptake

Recent experiments unexpectedly suggest that formate plays a critical role in chloride transport across cell membranes. In particular, active uptake of chloride in the renal proximal tubule cell occurs by chloride-formate exchange. Formate recycles from lumen to cell via nonionic diffusion of uncharged formic acid. In this manner, small amounts of formate can facilitate resorption of large quantities of chloride.

scholarly journals The Development of Molecular Biology of Osteoporosis

2021 ◽  
Vol 22 (15) ◽  
pp. 8182
Author(s):  
Yongguang Gao ◽  
Suryaji Patil ◽  
Jingxian Jia
Keyword(s):  
Bone Resorption ◽  
Molecular Biology ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Remodeling ◽  
Bone Cells ◽  
Cell Activity ◽  
Bone Cell ◽  
Bone Disorders ◽  
Molecular Aspects

Osteoporosis is one of the major bone disorders that affects both women and men, and causes bone deterioration and bone strength. Bone remodeling maintains bone mass and mineral homeostasis through the balanced action of osteoblasts and osteoclasts, which are responsible for bone formation and bone resorption, respectively. The imbalance in bone remodeling is known to be the main cause of osteoporosis. The imbalance can be the result of the action of various molecules produced by one bone cell that acts on other bone cells and influence cell activity. The understanding of the effect of these molecules on bone can help identify new targets and therapeutics to prevent and treat bone disorders. In this article, we have focused on molecules that are produced by osteoblasts, osteocytes, and osteoclasts and their mechanism of action on these cells. We have also summarized the different pharmacological osteoporosis treatments that target different molecular aspects of these bone cells to minimize osteoporosis.

Mitochondrial aquaporin-8 in renal proximal tubule cells: evidence for a role in the response to metabolic acidosis

2012 ◽  
Vol 303 (3) ◽  
pp. F458-F466 ◽  
Author(s):  
Sara M. Molinas ◽  
Laura Trumper ◽  
Raúl A. Marinelli
Keyword(s):  
Metabolic Acidosis ◽  
Protein Expression ◽  
Proximal Tubule ◽  
Ammonia Excretion ◽  
Renal Proximal Tubule ◽  
In Vivo Studies ◽  
Proximal Tubule Cell ◽  
Inner Mitochondrial Membrane ◽  
Ammonia Transport ◽  
In Cells

Mitochondrial ammonia synthesis in proximal tubules and its urinary excretion are key components of the renal response to maintain acid-base balance during metabolic acidosis. Since aquaporin-8 (AQP8) facilitates transport of ammonia and is localized in inner mitochondrial membrane (IMM) of renal proximal cells, we hypothesized that AQP8-facilitated mitochondrial ammonia transport in these cells plays a role in the response to acidosis. We evaluated whether mitochondrial AQP8 (mtAQP8) knockdown by RNA interference is able to impair ammonia excretion in the human renal proximal tubule cell line, HK-2. By RT-PCR and immunoblotting, we found that AQP8 is expressed in these cells and is localized in IMM. HK-2 cells were transfected with short-interfering RNA targeting human AQP8. After 48 h, the levels of mtAQP8 protein decreased by 53% ( P < 0.05). mtAQP8 knockdown decreased the rate of ammonia released into culture medium in cells grown at pH 7.4 (−31%, P < 0.05) as well as in cells exposed to acid (−90%, P < 0.05). We also evaluated mtAQP8 protein expression in HK-2 cells exposed to acidic medium. After 48 h, upregulation of mtAQP8 (+74%, P < 0.05) was observed, together with higher ammonia excretion rate (+73%, P < 0.05). In vivo studies in NH4Cl-loaded rats showed that mtAQP8 protein expression was also upregulated after 7 days of acidosis in renal cortex (+51%, P < 0.05). These data suggest that mtAQP8 plays an important role in the adaptive response of proximal tubule to acidosis possibly facilitating mitochondrial ammonia transport.

Expression of xenobiotic transporters in the human renal proximal tubule cell line RPTEC/TERT1

2015 ◽  
Vol 30 (1) ◽  
pp. 95-105 ◽  
Author(s):  
Lydia Aschauer ◽  
Giada Carta ◽  
Nadine Vogelsang ◽  
Eberhard Schlatter ◽  
Paul Jennings
Keyword(s):  
Proximal Tubule ◽  
Cell Line ◽  
Renal Proximal Tubule ◽  
Proximal Tubule Cell ◽  
Tubule Cell

ER stress contributes to renal proximal tubule injury by increasing SREBP-2-mediated lipid accumulation and apoptotic cell death

2012 ◽  
Vol 303 (2) ◽  
pp. F266-F278 ◽  
Author(s):  
Šárka Lhoták ◽  
Sudesh Sood ◽  
Elise Brimble ◽  
Rachel E. Carlisle ◽  
Stephen M. Colgan ◽  
...  
Keyword(s):  
Er Stress ◽  
Proximal Tubule ◽  
Lipid Accumulation ◽  
Cell Injury ◽  
Apoptotic Cell ◽  
Renal Proximal Tubule ◽  
Proximal Tubule Cell ◽  
Tubule Cell ◽  
Proximal Tubule Cells ◽  
Tubule Cells

Renal proximal tubule injury is induced by agents/conditions known to cause endoplasmic reticulum (ER) stress, including cyclosporine A (CsA), an immunosuppressant drug with nephrotoxic effects. However, the underlying mechanism by which ER stress contributes to proximal tubule cell injury is not well understood. In this study, we report lipid accumulation, sterol regulatory element-binding protein-2 (SREBP-2) expression, and ER stress in proximal tubules of kidneys from mice treated with the classic ER stressor tunicamycin (Tm) or in human renal biopsy specimens showing CsA-induced nephrotoxicity. Colocalization of ER stress markers [78-kDa glucose regulated protein (GRP78), CHOP] with SREBP-2 expression and lipid accumulation was prominent within the proximal tubule cells exposed to Tm or CsA. Prolonged ER stress resulted in increased apoptotic cell death of lipid-enriched proximal tubule cells with colocalization of GRP78, SREBP-2, and Ca2+-independent phospholipase A2 (iPLA2β), an SREBP-2 inducible gene with proapoptotic characteristics. In cultured HK-2 human proximal tubule cells, CsA- and Tm-induced ER stress caused lipid accumulation and SREBP-2 activation. Furthermore, overexpression of SREBP-2 or activation of endogenous SREBP-2 in HK-2 cells stimulated apoptosis. Inhibition of SREBP-2 activation with the site-1-serine protease inhibitor AEBSF prevented ER stress-induced lipid accumulation and apoptosis. Overexpression of the ER-resident chaperone GRP78 attenuated ER stress and inhibited CsA-induced SREBP-2 expression and lipid accumulation. In summary, our findings suggest that ER stress-induced SREBP-2 activation contributes to renal proximal tubule cell injury by dysregulating lipid homeostasis.

Phosphate uptake by primary renal proximal tubule cell cultures grown in hormonally defined medium

1985 ◽  
Vol 124 (3) ◽  
pp. 411-423 ◽  
Author(s):  
M. Anwar Waqar ◽  
Janny Seto ◽  
Soon Dong Chung ◽  
Sue Hiller-Grohol ◽  
Mary Taub
Keyword(s):  
Proximal Tubule ◽  
Cell Cultures ◽  
Phosphate Uptake ◽  
Defined Medium ◽  
Renal Proximal Tubule ◽  
Proximal Tubule Cell ◽  
Tubule Cell ◽  
Hormonally Defined Medium

scholarly journals Congener-Specific Polychlorinated Biphenyl–Induced Cell Death in Human Kidney Cells In Vitro: Potential Role of Caspase

2006 ◽  
Vol 25 (5) ◽  
pp. 341-347 ◽  
Author(s):  
Y. Q. Chen ◽  
S. De ◽  
S. Ghosh ◽  
S. K. Dutta
Keyword(s):  
Cell Death ◽  
Proximal Tubule ◽  
Human Kidney ◽  
Renal Proximal Tubule ◽  
Proximal Tubule Cell ◽  
Kidney Cells ◽  
Dependent Manner ◽  
Caspase Inhibitor ◽  
Pcb Congeners

Polychlorinated biphenyls (PCBs) are among the most widespread and persistent pollutants in the global environment. Coplanar and noncoplanar PCBs have been shown to cause congener-specific apoptosis mediated neurotoxicity in rats. Very few, if any, such studies have been reported on human renal cell toxicity. The authors report here caspase-dependent or caspase-independent renal toxicity, as measured by apoptotic death induced by PCBs, depending on the planarity of congeners PCB-77 (coplanar) and PCB-153 (noncoplanar) in human kidney cells (HK2) in vitro. The authors have combined morphological and biological techniques to discover the relevance of apoptosis in renal proximal tubule cell death induced by these two PCB congeners. Treatment with both PCB congeners caused accelerated apoptosis in a time-and concentration-dependent manner. Based on our findings using human kidney (HK2) cells, there was more apoptosis-mediated loss of cell viability by non– ortho-substituted PCB-77 when compared to PCB-153. A significant increase of caspase-3 expression through immunoblot studies showed the involvement of apoptosis by PCB-77 compared to none by PCB-153. The broad-spectrum caspase inhibitor z-VAD-fmk showed increased cell death when treated by PCB-153, but not by PCB-77, confirming that caspase inhibitor induced a switch in the mode of cell death. It is reasonable to assume that apoptotic cell death in the renal proximal tubule cells treated by PCBs may have both caspase-dependent and caspase-independent pathways.

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