BHK cells transfected with NCX3 are more resistant to hypoxia followed by reoxygenation than those transfected with NCX1 and NCX2: Possible relationship with mitochondrial membrane potential

Agnese Secondo, Rosaria Ilaria Staiano, Antonella Scorziello, Rossana Sirabella, Francesca Boscia, Annagrazia Adornetto, Valeria Valsecchi, Pasquale Molinaro, Lorella Maria Teresa Canzoniero, Gianfranco Di Renzo, Lucio Annunziato

Research output: Contribution to journalArticle

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Abstract

The specific role played by NCX1, NCX2, and NCX3, the three isoforms of the Na+/Ca2+ exchanger (NCX), has been explored during hypoxic conditions in BHK cells stably transfected with each of these isoforms. Six major findings emerged from the present study: (1) all the three isoforms were highly expressed on the plasma membranes of BHK cells; (2) under physiological conditions, the three NCX isoforms showed similar functional activity; (3) hypoxia plus reoxygenation induced a lower increase of [Ca2+]i in BHK-NCX3-transfected cells than in BHK-NCX1- and BHK-NCX2-transfected cells; (4) NCX3-transfected cells were more resistant to chemical hypoxia plus reoxygenation than NCX1- and NCX2-transfected cells. Interestingly, such augmented resistance was eliminated by CBDMD (10 μM), an inhibitor of NCX and by the specific silencing of the NCX3 isoform; (5) chemical hypoxia plus reoxygenation produced a loss of mitochondrial membrane potential in NCX1- and NCX2-transfected cells, but not in NCX3-transfected cells; (6) the forward mode of operation in NCX3-transfected cells was not affected by ATP depletion, as it occurred in NCX1- and NCX2-transfected cells. Altogether, these results indicate that the brain specifically expressed NCX3 isoform more significantly contributes to the maintenance of [Ca2+]i homeostasis during experimental conditions mimicking ischemia, thereby preventing mitochondrial Δψ collapses and cell death.

Original languageEnglish
Pages (from-to)521-535
Number of pages15
JournalCell Calcium
Volume42
Issue number6
DOIs
Publication statusPublished - Dec 2007

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Mitochondrial Membrane Potential
Protein Isoforms
Hypoxia
Homeostasis
Cell Death
Ischemia
Adenosine Triphosphate
Maintenance
Cell Membrane

Keywords

  • [Ca] homeostasis
  • Chemical hypoxia
  • Na-Ca exchanger
  • Neuroprotection

ASJC Scopus subject areas

  • Cell Biology
  • Endocrinology

Cite this

BHK cells transfected with NCX3 are more resistant to hypoxia followed by reoxygenation than those transfected with NCX1 and NCX2 : Possible relationship with mitochondrial membrane potential. / Secondo, Agnese; Staiano, Rosaria Ilaria; Scorziello, Antonella; Sirabella, Rossana; Boscia, Francesca; Adornetto, Annagrazia; Valsecchi, Valeria; Molinaro, Pasquale; Canzoniero, Lorella Maria Teresa; Di Renzo, Gianfranco; Annunziato, Lucio.

In: Cell Calcium, Vol. 42, No. 6, 12.2007, p. 521-535.

Research output: Contribution to journalArticle

Secondo, A, Staiano, RI, Scorziello, A, Sirabella, R, Boscia, F, Adornetto, A, Valsecchi, V, Molinaro, P, Canzoniero, LMT, Di Renzo, G & Annunziato, L 2007, 'BHK cells transfected with NCX3 are more resistant to hypoxia followed by reoxygenation than those transfected with NCX1 and NCX2: Possible relationship with mitochondrial membrane potential', Cell Calcium, vol. 42, no. 6, pp. 521-535. https://doi.org/10.1016/j.ceca.2007.01.006
Secondo, Agnese ; Staiano, Rosaria Ilaria ; Scorziello, Antonella ; Sirabella, Rossana ; Boscia, Francesca ; Adornetto, Annagrazia ; Valsecchi, Valeria ; Molinaro, Pasquale ; Canzoniero, Lorella Maria Teresa ; Di Renzo, Gianfranco ; Annunziato, Lucio. / BHK cells transfected with NCX3 are more resistant to hypoxia followed by reoxygenation than those transfected with NCX1 and NCX2 : Possible relationship with mitochondrial membrane potential. In: Cell Calcium. 2007 ; Vol. 42, No. 6. pp. 521-535.
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T1 - BHK cells transfected with NCX3 are more resistant to hypoxia followed by reoxygenation than those transfected with NCX1 and NCX2

T2 - Possible relationship with mitochondrial membrane potential

AU - Secondo, Agnese

AU - Staiano, Rosaria Ilaria

AU - Scorziello, Antonella

AU - Sirabella, Rossana

AU - Boscia, Francesca

AU - Adornetto, Annagrazia

AU - Valsecchi, Valeria

AU - Molinaro, Pasquale

AU - Canzoniero, Lorella Maria Teresa

AU - Di Renzo, Gianfranco

AU - Annunziato, Lucio

PY - 2007/12

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N2 - The specific role played by NCX1, NCX2, and NCX3, the three isoforms of the Na+/Ca2+ exchanger (NCX), has been explored during hypoxic conditions in BHK cells stably transfected with each of these isoforms. Six major findings emerged from the present study: (1) all the three isoforms were highly expressed on the plasma membranes of BHK cells; (2) under physiological conditions, the three NCX isoforms showed similar functional activity; (3) hypoxia plus reoxygenation induced a lower increase of [Ca2+]i in BHK-NCX3-transfected cells than in BHK-NCX1- and BHK-NCX2-transfected cells; (4) NCX3-transfected cells were more resistant to chemical hypoxia plus reoxygenation than NCX1- and NCX2-transfected cells. Interestingly, such augmented resistance was eliminated by CBDMD (10 μM), an inhibitor of NCX and by the specific silencing of the NCX3 isoform; (5) chemical hypoxia plus reoxygenation produced a loss of mitochondrial membrane potential in NCX1- and NCX2-transfected cells, but not in NCX3-transfected cells; (6) the forward mode of operation in NCX3-transfected cells was not affected by ATP depletion, as it occurred in NCX1- and NCX2-transfected cells. Altogether, these results indicate that the brain specifically expressed NCX3 isoform more significantly contributes to the maintenance of [Ca2+]i homeostasis during experimental conditions mimicking ischemia, thereby preventing mitochondrial Δψ collapses and cell death.

AB - The specific role played by NCX1, NCX2, and NCX3, the three isoforms of the Na+/Ca2+ exchanger (NCX), has been explored during hypoxic conditions in BHK cells stably transfected with each of these isoforms. Six major findings emerged from the present study: (1) all the three isoforms were highly expressed on the plasma membranes of BHK cells; (2) under physiological conditions, the three NCX isoforms showed similar functional activity; (3) hypoxia plus reoxygenation induced a lower increase of [Ca2+]i in BHK-NCX3-transfected cells than in BHK-NCX1- and BHK-NCX2-transfected cells; (4) NCX3-transfected cells were more resistant to chemical hypoxia plus reoxygenation than NCX1- and NCX2-transfected cells. Interestingly, such augmented resistance was eliminated by CBDMD (10 μM), an inhibitor of NCX and by the specific silencing of the NCX3 isoform; (5) chemical hypoxia plus reoxygenation produced a loss of mitochondrial membrane potential in NCX1- and NCX2-transfected cells, but not in NCX3-transfected cells; (6) the forward mode of operation in NCX3-transfected cells was not affected by ATP depletion, as it occurred in NCX1- and NCX2-transfected cells. Altogether, these results indicate that the brain specifically expressed NCX3 isoform more significantly contributes to the maintenance of [Ca2+]i homeostasis during experimental conditions mimicking ischemia, thereby preventing mitochondrial Δψ collapses and cell death.

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KW - Chemical hypoxia

KW - Na-Ca exchanger

KW - Neuroprotection

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