Amyloid beta peptide 1-40 stimulates the Na+/Ca2+ exchange activity of SNCX

Menjor Tino Unlap, Corey Williams, Darryl Morin, Brian Siroky, A. Fintha, Amanda Fuson, Layla Dodgen, Gergely Kovacs, Peter Komlosi, William Ferguson, Phillip Darwin Bell

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The Na+/Ca2+ exchangers, RNCX and SNCX, were cloned from mesangial cells of salt sensitive and salt resistant Dahl/Rapp rats, respectively, and differ at amino acid 218 (RNCXi/SNCXf) and in the exons expressed at the alternative splice site (RNCX B, D/SNCXB, D, F). These isoforms are also expressed in myocytes, neurons, and astrocytes where they maintain cytosolic calcium homeostasis. We demonstrated that cells expressing SNCX were more susceptible to oxidative stress than cells expressing RNCX. Others demonstrated that amyloid β peptide (Aβ) augments the adverse effects of oxidative stress on calcium homeostasis. Therefore, we sought to assess the effect of Aβ 1-40 on the abilities of OK-PTH cells stably expressing RNCX and SNCX and human glioma cells, SKMG1, to regulate cytosolic calcium homeostasis. Our studies showed that Aβ 1-40 (1 μM) did not affect RNCX activity, as assessed by changes in [Ca2+]i (Δ[Ca2+]i, 260 ± 10 nM to 267 ± 8 nM), while stimulating exchange activity 2.4 and 3 fold in cells expressing SNCX (100 ± 8 to 244 ± 12 nM) and in SKMG1 cells (90 ± 11 nM to 270 ± 18 nM), respectively. Our results also showed that Aβ 1-40, while not affecting the rate of Mn 2+ influx in cells expressing RNCX, stimulated the rate of Mn 2+ influx 2.8 and 2.9 fold in cells expressing SNCX and in SKMG1 cells. Thus, our studies demonstrate that Aβ-induced cytosolic calcium increase is mediated through certain isoforms of the Na+/Ca 2+ exchanger and reveals a possible mechanism by which Aβ 1-40 can alter cytosolic calcium homeostasis.

Original languageEnglish
Pages (from-to)3-12
Number of pages10
JournalCurrent Neurovascular Research
Volume2
Issue number1
DOIs
Publication statusPublished - Jan 2005

Fingerprint

Amyloid beta-Peptides
Calcium
Homeostasis
Protein Isoforms
Oxidative Stress
Sodium-Calcium Exchanger
Inbred Dahl Rats
RNA Splice Sites
Mesangial Cells
Amyloid
Glioma
Astrocytes
Muscle Cells
Exons
Salts
Neurons
Amino Acids

Keywords

  • Amyloid beta peptide
  • Cytosolic calcium
  • Na/Ca exchanger
  • Neuronal degeneration
  • Neurotoxicity

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Amyloid beta peptide 1-40 stimulates the Na+/Ca2+ exchange activity of SNCX. / Unlap, Menjor Tino; Williams, Corey; Morin, Darryl; Siroky, Brian; Fintha, A.; Fuson, Amanda; Dodgen, Layla; Kovacs, Gergely; Komlosi, Peter; Ferguson, William; Bell, Phillip Darwin.

In: Current Neurovascular Research, Vol. 2, No. 1, 01.2005, p. 3-12.

Research output: Contribution to journalArticle

Unlap, MT, Williams, C, Morin, D, Siroky, B, Fintha, A, Fuson, A, Dodgen, L, Kovacs, G, Komlosi, P, Ferguson, W & Bell, PD 2005, 'Amyloid beta peptide 1-40 stimulates the Na+/Ca2+ exchange activity of SNCX', Current Neurovascular Research, vol. 2, no. 1, pp. 3-12. https://doi.org/10.2174/1567202052773472
Unlap, Menjor Tino ; Williams, Corey ; Morin, Darryl ; Siroky, Brian ; Fintha, A. ; Fuson, Amanda ; Dodgen, Layla ; Kovacs, Gergely ; Komlosi, Peter ; Ferguson, William ; Bell, Phillip Darwin. / Amyloid beta peptide 1-40 stimulates the Na+/Ca2+ exchange activity of SNCX. In: Current Neurovascular Research. 2005 ; Vol. 2, No. 1. pp. 3-12.
@article{9fcd6eba0d5849aca8ef87714af11fca,
title = "Amyloid beta peptide 1-40 stimulates the Na+/Ca2+ exchange activity of SNCX",
abstract = "The Na+/Ca2+ exchangers, RNCX and SNCX, were cloned from mesangial cells of salt sensitive and salt resistant Dahl/Rapp rats, respectively, and differ at amino acid 218 (RNCXi/SNCXf) and in the exons expressed at the alternative splice site (RNCX B, D/SNCXB, D, F). These isoforms are also expressed in myocytes, neurons, and astrocytes where they maintain cytosolic calcium homeostasis. We demonstrated that cells expressing SNCX were more susceptible to oxidative stress than cells expressing RNCX. Others demonstrated that amyloid β peptide (Aβ) augments the adverse effects of oxidative stress on calcium homeostasis. Therefore, we sought to assess the effect of Aβ 1-40 on the abilities of OK-PTH cells stably expressing RNCX and SNCX and human glioma cells, SKMG1, to regulate cytosolic calcium homeostasis. Our studies showed that Aβ 1-40 (1 μM) did not affect RNCX activity, as assessed by changes in [Ca2+]i (Δ[Ca2+]i, 260 ± 10 nM to 267 ± 8 nM), while stimulating exchange activity 2.4 and 3 fold in cells expressing SNCX (100 ± 8 to 244 ± 12 nM) and in SKMG1 cells (90 ± 11 nM to 270 ± 18 nM), respectively. Our results also showed that Aβ 1-40, while not affecting the rate of Mn 2+ influx in cells expressing RNCX, stimulated the rate of Mn 2+ influx 2.8 and 2.9 fold in cells expressing SNCX and in SKMG1 cells. Thus, our studies demonstrate that Aβ-induced cytosolic calcium increase is mediated through certain isoforms of the Na+/Ca 2+ exchanger and reveals a possible mechanism by which Aβ 1-40 can alter cytosolic calcium homeostasis.",
keywords = "Amyloid beta peptide, Cytosolic calcium, Na/Ca exchanger, Neuronal degeneration, Neurotoxicity",
author = "Unlap, {Menjor Tino} and Corey Williams and Darryl Morin and Brian Siroky and A. Fintha and Amanda Fuson and Layla Dodgen and Gergely Kovacs and Peter Komlosi and William Ferguson and Bell, {Phillip Darwin}",
year = "2005",
month = "1",
doi = "10.2174/1567202052773472",
language = "English",
volume = "2",
pages = "3--12",
journal = "Current Neurovascular Research",
issn = "1567-2026",
publisher = "Bentham Science Publishers B.V.",
number = "1",

}

TY - JOUR

T1 - Amyloid beta peptide 1-40 stimulates the Na+/Ca2+ exchange activity of SNCX

AU - Unlap, Menjor Tino

AU - Williams, Corey

AU - Morin, Darryl

AU - Siroky, Brian

AU - Fintha, A.

AU - Fuson, Amanda

AU - Dodgen, Layla

AU - Kovacs, Gergely

AU - Komlosi, Peter

AU - Ferguson, William

AU - Bell, Phillip Darwin

PY - 2005/1

Y1 - 2005/1

N2 - The Na+/Ca2+ exchangers, RNCX and SNCX, were cloned from mesangial cells of salt sensitive and salt resistant Dahl/Rapp rats, respectively, and differ at amino acid 218 (RNCXi/SNCXf) and in the exons expressed at the alternative splice site (RNCX B, D/SNCXB, D, F). These isoforms are also expressed in myocytes, neurons, and astrocytes where they maintain cytosolic calcium homeostasis. We demonstrated that cells expressing SNCX were more susceptible to oxidative stress than cells expressing RNCX. Others demonstrated that amyloid β peptide (Aβ) augments the adverse effects of oxidative stress on calcium homeostasis. Therefore, we sought to assess the effect of Aβ 1-40 on the abilities of OK-PTH cells stably expressing RNCX and SNCX and human glioma cells, SKMG1, to regulate cytosolic calcium homeostasis. Our studies showed that Aβ 1-40 (1 μM) did not affect RNCX activity, as assessed by changes in [Ca2+]i (Δ[Ca2+]i, 260 ± 10 nM to 267 ± 8 nM), while stimulating exchange activity 2.4 and 3 fold in cells expressing SNCX (100 ± 8 to 244 ± 12 nM) and in SKMG1 cells (90 ± 11 nM to 270 ± 18 nM), respectively. Our results also showed that Aβ 1-40, while not affecting the rate of Mn 2+ influx in cells expressing RNCX, stimulated the rate of Mn 2+ influx 2.8 and 2.9 fold in cells expressing SNCX and in SKMG1 cells. Thus, our studies demonstrate that Aβ-induced cytosolic calcium increase is mediated through certain isoforms of the Na+/Ca 2+ exchanger and reveals a possible mechanism by which Aβ 1-40 can alter cytosolic calcium homeostasis.

AB - The Na+/Ca2+ exchangers, RNCX and SNCX, were cloned from mesangial cells of salt sensitive and salt resistant Dahl/Rapp rats, respectively, and differ at amino acid 218 (RNCXi/SNCXf) and in the exons expressed at the alternative splice site (RNCX B, D/SNCXB, D, F). These isoforms are also expressed in myocytes, neurons, and astrocytes where they maintain cytosolic calcium homeostasis. We demonstrated that cells expressing SNCX were more susceptible to oxidative stress than cells expressing RNCX. Others demonstrated that amyloid β peptide (Aβ) augments the adverse effects of oxidative stress on calcium homeostasis. Therefore, we sought to assess the effect of Aβ 1-40 on the abilities of OK-PTH cells stably expressing RNCX and SNCX and human glioma cells, SKMG1, to regulate cytosolic calcium homeostasis. Our studies showed that Aβ 1-40 (1 μM) did not affect RNCX activity, as assessed by changes in [Ca2+]i (Δ[Ca2+]i, 260 ± 10 nM to 267 ± 8 nM), while stimulating exchange activity 2.4 and 3 fold in cells expressing SNCX (100 ± 8 to 244 ± 12 nM) and in SKMG1 cells (90 ± 11 nM to 270 ± 18 nM), respectively. Our results also showed that Aβ 1-40, while not affecting the rate of Mn 2+ influx in cells expressing RNCX, stimulated the rate of Mn 2+ influx 2.8 and 2.9 fold in cells expressing SNCX and in SKMG1 cells. Thus, our studies demonstrate that Aβ-induced cytosolic calcium increase is mediated through certain isoforms of the Na+/Ca 2+ exchanger and reveals a possible mechanism by which Aβ 1-40 can alter cytosolic calcium homeostasis.

KW - Amyloid beta peptide

KW - Cytosolic calcium

KW - Na/Ca exchanger

KW - Neuronal degeneration

KW - Neurotoxicity

UR - http://www.scopus.com/inward/record.url?scp=26444538582&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=26444538582&partnerID=8YFLogxK

U2 - 10.2174/1567202052773472

DO - 10.2174/1567202052773472

M3 - Article

C2 - 16181095

AN - SCOPUS:26444538582

VL - 2

SP - 3

EP - 12

JO - Current Neurovascular Research

JF - Current Neurovascular Research

SN - 1567-2026

IS - 1

ER -