Characterization of renin-angiotensin system enzyme activities in cultured mouse podocytes

Bland, Alison M.; Arthur, John M.; Raymond, John R.; Janech, Michael G.

doi:10.1152/ajprenal.00050.2007

Cited by 82 publications

(98 citation statements)

References 55 publications

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“…Malpighian tubules were collected from at least 10 female mosquitoes and snap frozen as described above. The lysates were prepared by homogenizing the tubules in either 40 l of a 1ϫ Laemmli sample buffer or 30 l of a high-urea buffer containing the following: 4 M urea, 0.1% Triton X-100, 0.1% SDS, 150 mM NaCl, and 10 mM Tris · HCl, pH 7.4 (43,82). The high-urea lysates were then supplemented with an appropriate volume of a 5ϫ Laemmli sample buffer.…”

Section: Western Blotting Of Malpighian Tubulesmentioning

confidence: 99%

A SLC4-like anion exchanger from renal tubules of the mosquito (Aedes aegypti): evidence for a novel role of stellate cells in diuretic fluid secretion

Piermarini

Grogan

Lau

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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WITH THEIR ENRICHED EXPRESSION and activity of an apical vacuolar (V-type) H ϩ -ATPase (2, 52, 86), the principal cells of renal (Malpighian) tubules in the mosquito (Aedes aegypti) are similar to acid-secreting cells of the mammalian renal collecting tubule (85), mammalian male reproductive tract (10), turtle and amphibian urinary bladders (9), amphibian skin (17), and mammalian bone (76). In these acid-secreting cells, the apical V-type H ϩ -ATPase is often opposed by a basolateral Cl/HCO 3 anion exchanger of the solute-linked carrier 4 (SLC4) superfamily of bicarbonate transporters. The anion exchanger mediates the basolateral extrusion of intracellular HCO 3 Ϫ , thereby removing the intracellular HCO 3 Ϫ that was generated during the ionization of carbonic acid (H 2 CO 3 ).Disulfonic stilbene derivates, such as SITS and DIDS, are potent inhibitors of almost all SLC4 transporters (61). These negatively charged compounds are thought to interact with positively charged lysine residues on the external surface of SLC4 proteins (47, 83), perhaps blocking a conduit for anion translocation. Pharmacological studies using stilbene derivatives suggest the presence of Cl/HCO 3 exchangers in Malpighian tubules of some insects. For example, the addition of SITS to the peritubular bath of isolated Aedes Malpighian tubules lowers the unstimulated rates of fluid secretion (25), and both peritubular SITS and DIDS inhibit the serotoninstimulated rates of fluid secretion in isolated Malpighian tubules of Rhodnius prolixus (23,29). In isolated Malpighian tubules of the cricket (Teleogryllus oceanicus), SITS inhibits unstimulated rates of fluid secretion in the distal and main segments (89); DIDS also inhibits secretion in the distal segment, but it paradoxically stimulates secretion in the main segment (89). Finally, X-ray microanalysis on larval Drosophila Malpighian tubules indicate that DIDS decreases the intracellular Cl Ϫ concentration ([Cl Ϫ ]) in the basal cytoplasm of principal cells, which is consistent with the presence of a Cl/HCO 3 exchanger (88).To date, only one SLC4-like transporter has been cloned and characterized from any insect, i.e., the Na ϩ

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Section: Western Blotting Of Malpighian Tubulesmentioning

confidence: 99%

A SLC4-like anion exchanger from renal tubules of the mosquito (Aedes aegypti): evidence for a novel role of stellate cells in diuretic fluid secretion

Piermarini

Grogan

Lau

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…[25][26][27][28] Mesangial expression of Aogen and ACE has also been documented in renal tissue sections. 19,23 Mesangial cells synthesize Ang II 22,24 and aldosterone, the latter apparently through an Ang II-dependent mechanism.…”

Section: Intrarenal Raasmentioning

confidence: 99%

“…83 Thus, in vivo exposure of podocytes to aliskiren is predicted. As podocytes express a functional RAAS, [25][26][27][28] renin inhibition in these cells by aliskiren may Effect of aliskiren and enalapril on blood pressure (a) and albumin excretion (b) in mRen-2 rats. mRen-2 rats were treated with aliskiren or enalapril by subcutaneous osmotic minipumps.…”

Section: Testing Aliskiren In Animal Modelsmentioning

confidence: 99%

New insights into the renoprotective actions of the renin inhibitor aliskiren in experimental renal disease

Feldman

2010

Hypertens Res

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The renin-angiotensin-aldosterone system (RAAS) has a central function in the regulation of blood pressure. Aliskiren, the first direct renin inhibitor to be approved for the treatment of hypertension, blocks the RAAS at its point of activation. As renin inhibition acts at the top of the RAAS cascade, this mechanism has been proposed to offer advantages over existing modes of RAAS blockade. The RAAS is also considered to be a major factor in the pathogenesis of many renal diseases, especially diabetic nephropathy (DN), the main cause of end-stage renal disease. Existing therapies to block the RAAS slow the progression of DN, but they do not halt the disease. Therefore, more effective modes of interventions are needed. Studies to determine the efficacy of aliskiren in human renal disease are in progress. This review summarizes in vivo studies in which the efficacy of aliskiren was tested in experimental models of renal disease, and presents in vitro studies that provide insights into the possible mechanisms by which aliskiren confers renoprotection in animals. These works are discussed in the framework of the intrarenal RAAS and suggest that aliskiren may act by unique renoprotective mechanisms. Keywords: aliskiren; kidney; mechanism; nephropathy; renin INTRODUCTIONThe renin-angiotensin-aldosterone system (RAAS) is an ancient pathway 1 that has evolved into a central mechanism by which mammalian blood pressure (BP) and fluid homeostasis are regulated. Research in this field started with the discovery in 1898 by Tigerstedt and Berman 2 that a renal extract when injected into rabbits induced a rapid increase in systemic BP. Subsequent work over many years established the RAAS as a pivotal contributor to cardiorenal diseases. Hence, inhibitors of the middle and distal portions of the RAAS pathway, angiotensin-converting enzyme (ACE) inhibitors (ACEI) and AT 1 receptor blockers, respectively, have become mainstay therapies for treating hypertension. In 2007, aliskiren, the first direct renin inhibitor (DRI), was approved for the treatment of hypertension. This heralded the therapeutic control of BP by inhibiting the RAAS at its first and rate-limiting step. However, RAAS blockade is also effective for treating renal disease 3-6 and the efficacy of aliskiren for this purpose is currently being investigated. Accordingly, the subject of this review is to summarize the preclinical evidence for renoprotection by aliskiren, and to discuss recently published information on the possible mechanism(s) for these benefits. As it is well recognized that there is a tissue as well as circulating RAAS, 7 the preclinical actions of aliskiren will be discussed in the context of the intrarenal RAAS and the potential for its inhibition by aliskiren.

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“…In SHRs administered captopril (20 mg/kg body weight, positive control), the SBP significantly decreased by 16.4±3.9 mmHg (p<0.01) at 4h after administration. The mean SBP of the SHRs administered the 40% CH 3 CN fraction (250 mg/kg body weight) significantly decreased by 11.7±4.7 mmHg (p<0.05) and 5.0±5.2 mmHg (p<0.01) at 4 and 8 h after adused as an external standard for mass number (Velez et al, 2007).…”

Section: Methodsmentioning

confidence: 93%

Chemical Nature of a New Antihypertensive Peptide Derived from Jellyfish

Morinaga

Iwai

Tomita

et al. 2010

FSTR

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A high-concentration (20%) antihypertensive peptide solution with angiotensin I-converting enzyme (ACE) inhibitory activity was prepared from the powder of the jellyfish Stomolophus nomurai, a plague of which had recently hit Japan's fishing industry, using the drum dryer method. Three active fractions, Fr. 3-1, Fr. 3-3, and Fr. 3-6, were isolated from the peptide mixture by step-wise elution by Sep-Pak Vac C 18 and further fractionated by high-performance liquid chromatography twice. The sequences of Fr. 3-1, Fr. 3-3, and Fr. 3-6 were determined as IGDEPLANYL, FGGIDDINQIGQSD, and YYAPFE, respectively. The most active peptide was identified with the synthetic peptide YYAPFE by sequence analysis, MALDI-TOF MS, and NMR spectra. Further, YYAPFQ, designed and synthesized on the basis of YYAPFE, showed the highest ACE inhibitory activity in vitro among YYAPFE, YYAPF, YYAP, YYA, and YY; however, its effect on systolic blood pressure showed a similar tendency to that of YYAPFE in spontaneously hypertensive rats.

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Characterization of renin-angiotensin system enzyme activities in cultured mouse podocytes

Cited by 82 publications

References 55 publications

A SLC4-like anion exchanger from renal tubules of the mosquito (Aedes aegypti): evidence for a novel role of stellate cells in diuretic fluid secretion

A SLC4-like anion exchanger from renal tubules of the mosquito (Aedes aegypti): evidence for a novel role of stellate cells in diuretic fluid secretion

New insights into the renoprotective actions of the renin inhibitor aliskiren in experimental renal disease

Chemical Nature of a New Antihypertensive Peptide Derived from Jellyfish

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