Foot processes

BisHov s J, MASUOKA Y and KAPSALis J G (1977) Antioxidant effect of spices, herbs and protein Hydrolyzates in freeze-dried model systems Synergistic action with synthetic phenolic antioxidants, J Foot/ Processing Preservation, 1, 153-66. 

Fig. 15.2 Diagram showing a transverse cross-section of a cerebral capillary. The endothelial cells, responsible for the main barrier properties of the blood-brain barrier are separated from the astrocyte foot processes, pericytes and occasional neurons by the basement membrane. All these components make up the blood-brain barrier.

Pericytes lie periendothelially on the abluminal side of the microvessels (Figure 15.3). A layer of basement membrane separates the pericytes from the endothelial cells and the astrocyte foot processes. Pericytes send out cell processes which penetrate the basement membrane and cover around 20-30% of the micro-vascular circumference [18]. Pericyte cytoplasmic projections encircling the endothelial cells provide both a vasodynamic capacity and structural support to the microvasculature. They bear receptors for vasoactive mediators such as catecholamines, endothelin-1, VIP, vasopressin and angiotensin II. Pericytes become mark-... 

Fig. 15.3 D iagram showing a longitudinal cross-section of the blood-brain barrier, with the brain capillary endothelial cells sealed by the tight junctions and surrounded by pericytes and astrocyte foot processes. These cellular components of the BBB are separated by a basement membrane.

Golden PL, Pardridge WM. P-glycopro-tein on astrocyte foot processes of unfixed isolated human brain capillaries. Brain Res 1999 819 143-146. 

Conventional electron microscopy (Devine et al 1972) and freeze-etch (Somlyo Franzini-Armstrong 1985) of VSMCs reveals that the jSR is separated from overlying PL by a 12—15nm cytosolic space that is traversed by electron-dense structures. These structures appear similar to the foot processes of cardiac and skeletal muscle (Franzini-Armstrong et al 1998). Indeed, there is striking structural similarity between these PL—jSR regions in VSMC and the diads and triads of cardiac and skeletal muscle (Franzini-Armstrong et al 1998). Moreover,... 

Figure 17.1 Schematic cross section of a brain capillary formed by endothelial cells which are surrounded by pericytes and foot processes of astrocytes. Endothelial cells express various ABC-transport proteins at their luminal surface which significantly contribute to the barrier function.

The blood-brain barrier is markedly different from peripheral capillaries Peripheral capillaries are fenestrated with openings up to 50 nm wide. In contrast, cerebral endothelial cells are closely connected by tight junctions and zonulae occludentes, resulting in extremely high transendothelial resistances of up to 1500-2000 12 cm2 [16] (Figure 17.1). The capillaries are surrounded by a basal membrane enclosing intermittently pericytes, which have been postulated to be involved in host defense. The outer surface of the basement membrane is covered by astrocytic foot processes. Most likely, secretion of soluble growth factors by astrocytes plays an important role in endothelial cell differentiation. 

T-system membrane results in an interaction between the T-tubules and the SR at specialised junctions, known as excitation-contraction coupling units. Here the two membranes are finked by a foot process consisting of two Ca ion channels that function in concert. 

Smoyer, W. E., Mundel, P., Gupta, A., and Welsh, M. J. (1997). Podocyte alpha-actinin induction precedes foot process effacement in experimental nephrotic syndrome. Am.J. Physiol. 273, F150-157. 

The glomerular capillary wall has a very high hydraulic permeability and the glomerular basement membrane and the slit diaphragm probably contribute approximately 50% each to the total hydraulic resistance of the capillary wall (D8). Foot process effacement found both in experimental models of nephrotic syndrome and in human glomerulopathies dramatically reduces the hydraulic permeability of the glomerular capillary wall (Gil). 

Podocytes are polarized cells, so one can differentiate between luminal and abluminal (basal) membrane domains (the basal domain corresponds to the sole plates of the foot processes, which are embedded in the basement membrane). The slit diaphragm forms the border between the luminal and the abluminal membranes. 

Contractile elements of the podocyte foot processes, which may influence the hydraulic permeability of the glomerular capillary wall, may be regulated via vasoactive hormones. Receptors for some vasoactive hormones, for example, en-dothelin (R4), atrial natriuretic peptide (S9), nitric oxide (K22), and angiotensin n (Yl), have been described on the podocyte surface. 

Vasoactive hormones can influence the contractility and the structure of podocyte foot processes. An increase of intracellular calcium and cAMP in podocytes leads to contraction of foot processes and a decrease of Kf, whereas an increase of cGMP can act in the opposite direction (S9). Vasoactive hormones can also change the charge on the podocyte surface and so facilitate proteinuria (P2). 

The cytoplasmic part of nephrin interacts also with ZO-1 protein and actin (K10). Interaction of the antibody or toxin with the extracellular part of nephrin could thus also result in intracellular signaling (phophorylation of tyrosine residues in the cytoplasmic part of nephrin), change of the actin cytoskeleton, and foot process fusion. Indeed, increased levels of phosphotyrosine were demonstrated in renal biopsies of patients with minimal change disease and membranous nephropathy (B2). 

Congenital nephrotic syndrome of the Finnish type is clinically characterized by heavy proteinuria present already in utero, which leads without nephrectomy and renal replacement therapy to the death of the affected children usually before the second year of life. Electronoptically, the glomerular basement membrane seems to be intact with the fusion of the podocyte foot processes. The chemical composition of the glomerular basement membrane is normal in patients with congenital nephrotic syndrome and all genes of the main proteins of the glomerular... 

Minimal change disease is the most common cause of nephrotic syndrome in children, presenting typically with rapid onset of mostly steroid-sensitive nephrotic syndrome, usually with selective proteinuria (albuminuria). Light-microscopic morphology of the kidney is normal and immunofluorescence is negative. Foot process effacement on electron microscopy is the only observed pathology. 

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