neuropeptide-y and Kidney-Diseases

The presence in the mammalian kidney of NPY and at least one of its receptor subtypes has been proven by several independent methodologies. Also, numerous studies using physiological and pharmacological approaches indicated that this peptide has the capacity to alter renal function. In particular, these studies suggest that NPY may exert renal vasoconstrictor and tubular actions that are species dependent, and may also influence renin secretion by the kidney. The question whether NPY plays an important role in the physiological regulation of renal hemodynamics and electrolyte excretion, remains largely unanswered at present. No major impairments in renal function have been reported in genetically models deficient in NPY or its Y1 receptor. Thus, additional studies are required to elucidate the role of NPY in the physiological and pathophysiological regulation of renal function.

Topics: Animals; Humans; Kidney; Kidney Diseases; Kidney Function Tests; Neuropeptide Y; Receptors, Neuropeptide Y

Albuminuria is an independent risk factor for the progression to end-stage kidney failure, cardiovascular morbidity, and premature death. As such, discovering signaling pathways that modulate albuminuria is desirable. Here, we studied the transcriptomes of podocytes, key cells in the prevention of albuminuria, under diabetic conditions. We found that

Topics: Albuminuria; Animals; Arginine; Benzazepines; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Disease Models, Animal; Down-Regulation; Doxorubicin; Humans; Insulin; Kidney Diseases; Kidney Glomerulus; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Neuropeptide Y; Podocytes; Proteomics; Receptors, Neuropeptide Y; Signal Transduction

Cisplatin is a platinum-based chemotherapeutic drug for treating various types of cancers. However, the use of cisplatin is limited by its negative effect on normal tissues, particularly nephrotoxicity. Various mechanisms such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and apoptosis are involved in the adverse effect induced by cisplatin treatment. Several studies have suggested that neuropeptide Y (NPY) is involved in neuroprotection as well as restoration of bone marrow dysfunction from chemotherapy induced nerve injury. However, the role of NPY in chemotherapy- induced nephrotoxicity has not been studied. Here, we show that NPY rescues renal dysfunction by reducing the expression of pro-apoptotic proteins in cisplatin induced nephrotoxicity through Y1 receptor, suggesting that NPY can protect kidney against cisplatin nephrotoxicity as a possible useful agent to prevent and treat cisplatin-induced nephrotoxicity. [BMB Reports 2016; 49(5): 288-292].

Topics: Animals; Apoptosis; Cisplatin; Down-Regulation; Female; Kidney; Kidney Diseases; Male; Mice, Inbred C57BL; Neuropeptide Y; Protective Agents; Receptors, Neuropeptide Y; Signal Transduction; Tumor Suppressor Protein p53

Neuropeptide Y (NPY) is a key modulator of the autonomic nervous system playing pivotal roles in cardiovascular and neuronal functions. In this study, we assessed the cellular localization and gene expression of NPY in rat kidneys. We also examined the relationship between NPY gene expression and renin in two rat models of hypertension (two-kidney, one-clip renal hypertension (2K1C), and deoxycorticosterone-salt-induced hypertension (DOCA-salt)) characterized by a similar blood pressure elevation. In situ hybridization and immunohistochemistry, using anti-NPY or anti-C-flanking peptide of NPY (CPON) antibodies, showed that NPY transcript and protein were colocalized in the tubules of rat kidneys. During experimental hypertension, NPY mRNA was decreased in both kidneys of the 2K1C animals, but not in the kidney of DOCA-salt rats. In 2K1C rats, renal NPY content was also decreased. The difference in NPY gene expression between 2K1C rats (a high renin model of hypertension) and DOCA-salt rats (a low renin model of hypertension) suggests that circulating angiotensin II plays a role in local renal NPY gene expression and that the elevated blood pressure per se is not the primary factor responsible for the control of NPY gene expression in the kidney.

Topics: Animals; Body Weight; Gene Expression; Gene Expression Regulation; Hemodynamics; Hypertension, Renal; Immunohistochemistry; Kidney; Kidney Diseases; Neuropeptide Y; Rats; Rats, Wistar; Renin; RNA, Messenger

We produced and characterized three anti-C-flanking peptides of neuropeptide Y (CPON) monoclonal antibodies. The Ka for these antibodies ranged from 0.4 to 0.8 x 10(8) l/mol with an IC50 for CPON(1-30) at about 20 nM as determined by ELISA. All these antibodies are IgG1 and recognize the 16-30 part of CPON. These antibodies and a specific anti-NPY monoclonal antibody were used to study the localization of CPON and NPY in the human kidney. The avidin-biotin technique was employed. NPY and CPON immunoreactivities were present in large amount in the renal tubules of the human kidney but not in the glomeruli. No labeling was found within the renal arterioles and veins, but some immunoreactivity was evidenced in the perivascular area. Because no specific receptor for CPON has been described to date, the presence of this peptide in the tubules may be due to a tubular reabsorption or perhaps to a local synthesis of pro-NPY.

Topics: Adrenal Gland Neoplasms; Antibodies, Monoclonal; Antibody Specificity; Biopsy; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Graft Rejection; Humans; Immunoglobulin G; Immunohistochemistry; Kidney; Kidney Diseases; Kidney Glomerulus; Kidney Transplantation; Kidney Tubules; Neuropeptide Y; Peptide Fragments; Pheochromocytoma; Sensitivity and Specificity

A radioimmunoassay has been developed for measuring plasma neuropeptide-Y immunoreactivity using extraction on Sep-Pak C18 cartridges. Neuropeptide-Y concentrations (mean +/- SEM) in plasma from 15 normotensive individuals were 223.6 +/- 14.7 ng/l. Plasma concentrations were raised in 10 patients with heamodialysis-dependent chronic renal failure with values of 417.6 +/- 13.6 ng/l and in 3 patients with phaeochromocytoma the concentrations were 237 ng/l, 574 ng/l and 747 ng/l. Plasma neuropeptide-Y immunoreactivity was also measured in 10 normotensive individuals in response to a, hand-in-ice, cold pressor test. Despite an immediate significant elevation in blood pressure, neuropeptide-Y immunoreactivity was not significantly raised until after the removal of the hand from the ice by which time the blood pressure had returned towards the basal levels. This dissociation in neuropeptide-Y immunoreactivity and blood pressure responses probably reflects a delay in the diffusion of synaptic neuropeptide-Y into the general circulation. This study suggests that the measurement of neuropeptide-Y immunoreactivity may be a useful index of sympathetic activation.

Topics: Adult; Blood Pressure; Cold Temperature; Female; Humans; Kidney Diseases; Male; Neuropeptide Y; Radioimmunoassay; Sympathetic Nervous System