Puromycin Aminonucleoside Induces Glomerular Epithelial Cell Apoptosis

Sanwal, Vibha; Pandya, Manish; Bhaskaran, Madhu; Franki, Nicholas; Reddy, Krishna; Ding, Guohua; Kapasi, Aditi A.; Valderrama, Elsa; Singhal, Pravin C.

doi:10.1006/exmp.2000.2345

Cited by 44 publications

(41 citation statements)

References 29 publications

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“…Other mediators of podocyte apoptosis have been shown. For example, puromycin induces podocyte apoptosis in culture, which is mediated through reactive oxygen species (122). Taken together, these studies show that apoptosis increases in podocytes under certain circumstances and contributes to the loss of cell number.…”

Section: Apoptosismentioning

confidence: 71%

Podocyte Biology and Response to Injury

Mündel¹,

Shankland²

2002

Journal of the American Society of Nephrology

595

541

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The visceral glomerular epithelial cell, also called podocyte, is a terminally differentiated cell that lines the outer aspect of the glomerular basement membrane (GBM). It therefore forms the final barrier to protein loss, which explains why podocyte injury is typically associated with marked proteinuria. Indeed, all forms of nephrotic syndrome are characterized by abnormalities in the podocyte. In this review, we will provide an update of the known functions of recent podocyte-specific proteins and focus on the slit diaphragm (SD) and the mechanisms underlying foot process (FP) flattening and how the podocyte responds to injury. Molecular Anatomy of the Podocyte FP CytoskeletonPodocyte FP are not static, but rather contain a contractile system similar to that seen in pericytes. This contractile apparatus is composed of actin, myosin-II, ␣-actinin-4, talin, and vinculin (1). The actin filament bundles form arches between adjacent FP of the same podocyte (2). Figure 1 is a schema of our current understanding of the molecular composition of the cytoskeleton in podocyte FP. Importantly, the actin filaments are connected to the underlying GBM at focal contacts via an ␣3␤1 integrin complex (3,4). The bends of the actin filament arches appear to be connected directly to the microtubules of the major processes (own unpublished results). FP are anchored to the GBM via ␣3␤1 integrin (5) and dystroglycans (6,7). Neighboring FP are connected by a cell-cell junction, the glomerular SD, which represents the main size selective filter barrier in the kidney (8 -10). The SD is thought to be a modified adherens junction (11) that is composed of a growing number of proteins, including nephrin (12-14), P-cadherin, CD2AP (15-18), , FAT (20), podocin (16,21), and possibly Neph1 (see reference 22 and below). In addition to the contractile proteins described above, we have reported the association of synaptopodin with the actin filaments in FP (23). Synaptopodin is the first member of a novel class of prolinerich proteins (24) and, like ␣-actinin-4, interacts with the tight junction protein MAGI-1 (25) that is also expressed in podocytes (26). Four Major Causes of FP EffacementThe basolateral portion of the foot processes represents the center of podocyte function and is defined by three membrane domains: the apical membrane domain, the SD protein complex, and the basal membrane domain or sole plate (27). The submembranous regions of all compartments are connected to the FP actin cytoskeleton, e.g., on the apical membrane domain, podocalyxin associates with the actin cytoskeleton through interactions with ezrin and the actin cytoskeleton via Na ϩ /H ϩ -exchanger regulatory factor 2 (NHERF2), a scaffold protein containing two PDZ (PSD-95/Dlg/ZO-1) domains and an ERM-binding region (28,29). The FP actin cytoskeleton is highly dynamic and ultimately determines the structural maintenance of the filtration slits as demonstrated in the acute PS/heparin model by several groups (30 -32). Interference with one of the three domains eventually ...

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Section: Apoptosismentioning

confidence: 71%

Podocyte Biology and Response to Injury

Mündel¹,

Shankland²

2002

Journal of the American Society of Nephrology

595

541

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“…[5][6][7][8] CD2AP, the key proteins of podocyte slit diaphragm (SD), together form a signal transduction complex by interacting with other SD molecules and also play an important role in maintaining SD structural and functional integrity. [9][10][11] Data suggest that podocyte injury or SD structural damage will inevitably result in proteinuria. Proteinuria is a hallmark of loss of the glomerulus' permselectivity.…”

Section: Discussionmentioning

confidence: 99%

Role of CD2-associated protein in podocyte apoptosis and proteinuria induced by angiotensin II

Huang

You

2014

Renal Failure

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Podocytes are highly differentiated epithelial cells that form interdigitating foot processes with bridging slit diaphragms (SDs) that regulate renal ultrafiltration. Proteinuria is the most common clinical manifestation of glomerular diseases. Losartan is the traditional reninangiotensin system (RAS). However; the precise mechanisms underlying the beneficial effects of Losartan on podocytes are still unknown. This study tested the hypothesis that podocytes were exposed to Angiotensin II (Ang II) to induce apoptosis and Proteinuria. Losartan directly reduces the rate of apoptotic podocytes induced by Ang II. Our results showed that apoptotic podocytes may be related to the decrease of CD2AP mRNA and protein expressions, Losartan reduced the apoptosis and Proteinuria by stabilizing the CD2AP mRNA and protein expressions. In this study, we explored the role of CD2-associated protein in podocyte apoptosis and Proteinuria induced by Ang II. Our findings provide some possible clues for further exploring the pharmacological targets to the proteinuria.

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“…Therefore, it is of major interest to investigate the mechanisms that lead to podocyte depletion. In PAN, apoptosis in podocytes can be partially inhibited by ROS scavengers and by actinomycin D. In addition, necrosis of podocytes was found when high concentrations of puromycin aminonucleoside (PA) were used (118,390). During PAN-induced FSGS, apoptosis of podocytes was accompanied by an increase of Bcl-2 expression.…”

Section: B Puromycin Aminonucleoside-induced Nephrosismentioning

confidence: 99%

Cell Biology of the Glomerular Podocyte

Pavenstädt

Kriz

Kretzler

2003

Physiological Reviews

1,309

1,278

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Glomerular podocytes are highly specialized cells with a complex cytoarchitecture. Their most prominent features are interdigitated foot processes with filtration slits in between. These are bridged by the slit diaphragm, which plays a major role in establishing the selective permeability of the glomerular filtration barrier. Injury to podocytes leads to proteinuria, a hallmark of most glomerular diseases. New technical approaches have led to a considerable increase in our understanding of podocyte biology including protein inventory, composition and arrangement of the cytoskeleton, receptor equipment, and signaling pathways involved in the control of ultrafiltration. Moreover, disturbances of podocyte architecture resulting in the retraction of foot processes and proteinuria appear to be a common theme in the progression of acquired glomerular disease. In hereditary nephrotic syndromes identified over the last 2 years, all mutated gene products were localized in podocytes. This review integrates our recent physiological and molecular understanding of the role of podocytes during the maintenance and failure of the glomerular filtration barrier.

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Puromycin Aminonucleoside Induces Glomerular Epithelial Cell Apoptosis

Cited by 44 publications

References 29 publications

Podocyte Biology and Response to Injury

Podocyte Biology and Response to Injury

Role of CD2-associated protein in podocyte apoptosis and proteinuria induced by angiotensin II

Cell Biology of the Glomerular Podocyte

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