author_facet Miller, R. Lance
Sandoval, Pablo C.
Pisitkun, Trairak
Knepper, Mark A.
Hoffert, Jason D.
Miller, R. Lance
Sandoval, Pablo C.
Pisitkun, Trairak
Knepper, Mark A.
Hoffert, Jason D.
author Miller, R. Lance
Sandoval, Pablo C.
Pisitkun, Trairak
Knepper, Mark A.
Hoffert, Jason D.
spellingShingle Miller, R. Lance
Sandoval, Pablo C.
Pisitkun, Trairak
Knepper, Mark A.
Hoffert, Jason D.
American Journal of Physiology-Renal Physiology
Vasopressin inhibits apoptosis in renal collecting duct cells
Physiology
author_sort miller, r. lance
spelling Miller, R. Lance Sandoval, Pablo C. Pisitkun, Trairak Knepper, Mark A. Hoffert, Jason D. 1931-857X 1522-1466 American Physiological Society Physiology http://dx.doi.org/10.1152/ajprenal.00431.2012 <jats:p>The peptide hormone arginine vasopressin (AVP) plays a critical role in regulating salt and water transport in the mammalian kidney. Recent studies have also demonstrated that AVP can promote cell survival in neuronal cells through V1 receptors. The current study addresses whether AVP can inhibit apoptosis in kidney collecting duct cells via V2 receptors and also explores the downstream signaling pathways regulating this phenomenon. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling analysis and caspase cleavage assays demonstrated that 1-desamino-8-d-arginine vasopressin (dDAVP) inhibited apoptosis induced by various agents (staurosporine, actinomycin D, and cycloheximide) in cultured mouse cortical collecting duct cells (mpkCCD). Incubation with dDAVP also inhibited apoptosis induced by the phosphatidylinositol 3-kinase (PI3K) pathway inhibitor LY294002, suggesting that the antiapoptotic effects of dDAVP are largely independent of PI3K signaling. The V2 receptor antagonist SR121463 completely abolished the antiapoptotic effects of dDAVP. In addition, incubation with 8-cpt-cAMP, a cell-permeable analog of cAMP, reproduced the antiapoptotic effects of dDAVP. Both dDAVP and 8-cpt-cAMP increased phosphorylation of proapoptotic Bcl-2 family members Bad and Bok. Bad phosphorylation at Ser-112 and Ser-155 is known to inhibit its proapoptotic activity. Preincubation with H89 blocked dDAVP-induced phosphorylation of both Bad and Bok, suggesting dependence on protein kinase A (PKA). This study provides evidence that AVP can inhibit apoptosis through the V2 receptor and downstream cAMP-mediated pathways in mammalian kidney. The antiapoptotic action of AVP may be relevant to a number of physiological and pathophysiological conditions including osmotic tolerance in the inner medulla, escape from AVP-induced antidiuresis, and polycystic kidney disease.</jats:p> Vasopressin inhibits apoptosis in renal collecting duct cells American Journal of Physiology-Renal Physiology
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title Vasopressin inhibits apoptosis in renal collecting duct cells
title_unstemmed Vasopressin inhibits apoptosis in renal collecting duct cells
title_full Vasopressin inhibits apoptosis in renal collecting duct cells
title_fullStr Vasopressin inhibits apoptosis in renal collecting duct cells
title_full_unstemmed Vasopressin inhibits apoptosis in renal collecting duct cells
title_short Vasopressin inhibits apoptosis in renal collecting duct cells
title_sort vasopressin inhibits apoptosis in renal collecting duct cells
topic Physiology
url http://dx.doi.org/10.1152/ajprenal.00431.2012
publishDate 2013
physical F177-F188
description <jats:p>The peptide hormone arginine vasopressin (AVP) plays a critical role in regulating salt and water transport in the mammalian kidney. Recent studies have also demonstrated that AVP can promote cell survival in neuronal cells through V1 receptors. The current study addresses whether AVP can inhibit apoptosis in kidney collecting duct cells via V2 receptors and also explores the downstream signaling pathways regulating this phenomenon. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling analysis and caspase cleavage assays demonstrated that 1-desamino-8-d-arginine vasopressin (dDAVP) inhibited apoptosis induced by various agents (staurosporine, actinomycin D, and cycloheximide) in cultured mouse cortical collecting duct cells (mpkCCD). Incubation with dDAVP also inhibited apoptosis induced by the phosphatidylinositol 3-kinase (PI3K) pathway inhibitor LY294002, suggesting that the antiapoptotic effects of dDAVP are largely independent of PI3K signaling. The V2 receptor antagonist SR121463 completely abolished the antiapoptotic effects of dDAVP. In addition, incubation with 8-cpt-cAMP, a cell-permeable analog of cAMP, reproduced the antiapoptotic effects of dDAVP. Both dDAVP and 8-cpt-cAMP increased phosphorylation of proapoptotic Bcl-2 family members Bad and Bok. Bad phosphorylation at Ser-112 and Ser-155 is known to inhibit its proapoptotic activity. Preincubation with H89 blocked dDAVP-induced phosphorylation of both Bad and Bok, suggesting dependence on protein kinase A (PKA). This study provides evidence that AVP can inhibit apoptosis through the V2 receptor and downstream cAMP-mediated pathways in mammalian kidney. The antiapoptotic action of AVP may be relevant to a number of physiological and pathophysiological conditions including osmotic tolerance in the inner medulla, escape from AVP-induced antidiuresis, and polycystic kidney disease.</jats:p>
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author Miller, R. Lance, Sandoval, Pablo C., Pisitkun, Trairak, Knepper, Mark A., Hoffert, Jason D.
author_facet Miller, R. Lance, Sandoval, Pablo C., Pisitkun, Trairak, Knepper, Mark A., Hoffert, Jason D., Miller, R. Lance, Sandoval, Pablo C., Pisitkun, Trairak, Knepper, Mark A., Hoffert, Jason D.
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description <jats:p>The peptide hormone arginine vasopressin (AVP) plays a critical role in regulating salt and water transport in the mammalian kidney. Recent studies have also demonstrated that AVP can promote cell survival in neuronal cells through V1 receptors. The current study addresses whether AVP can inhibit apoptosis in kidney collecting duct cells via V2 receptors and also explores the downstream signaling pathways regulating this phenomenon. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling analysis and caspase cleavage assays demonstrated that 1-desamino-8-d-arginine vasopressin (dDAVP) inhibited apoptosis induced by various agents (staurosporine, actinomycin D, and cycloheximide) in cultured mouse cortical collecting duct cells (mpkCCD). Incubation with dDAVP also inhibited apoptosis induced by the phosphatidylinositol 3-kinase (PI3K) pathway inhibitor LY294002, suggesting that the antiapoptotic effects of dDAVP are largely independent of PI3K signaling. The V2 receptor antagonist SR121463 completely abolished the antiapoptotic effects of dDAVP. In addition, incubation with 8-cpt-cAMP, a cell-permeable analog of cAMP, reproduced the antiapoptotic effects of dDAVP. Both dDAVP and 8-cpt-cAMP increased phosphorylation of proapoptotic Bcl-2 family members Bad and Bok. Bad phosphorylation at Ser-112 and Ser-155 is known to inhibit its proapoptotic activity. Preincubation with H89 blocked dDAVP-induced phosphorylation of both Bad and Bok, suggesting dependence on protein kinase A (PKA). This study provides evidence that AVP can inhibit apoptosis through the V2 receptor and downstream cAMP-mediated pathways in mammalian kidney. The antiapoptotic action of AVP may be relevant to a number of physiological and pathophysiological conditions including osmotic tolerance in the inner medulla, escape from AVP-induced antidiuresis, and polycystic kidney disease.</jats:p>
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spelling Miller, R. Lance Sandoval, Pablo C. Pisitkun, Trairak Knepper, Mark A. Hoffert, Jason D. 1931-857X 1522-1466 American Physiological Society Physiology http://dx.doi.org/10.1152/ajprenal.00431.2012 <jats:p>The peptide hormone arginine vasopressin (AVP) plays a critical role in regulating salt and water transport in the mammalian kidney. Recent studies have also demonstrated that AVP can promote cell survival in neuronal cells through V1 receptors. The current study addresses whether AVP can inhibit apoptosis in kidney collecting duct cells via V2 receptors and also explores the downstream signaling pathways regulating this phenomenon. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling analysis and caspase cleavage assays demonstrated that 1-desamino-8-d-arginine vasopressin (dDAVP) inhibited apoptosis induced by various agents (staurosporine, actinomycin D, and cycloheximide) in cultured mouse cortical collecting duct cells (mpkCCD). Incubation with dDAVP also inhibited apoptosis induced by the phosphatidylinositol 3-kinase (PI3K) pathway inhibitor LY294002, suggesting that the antiapoptotic effects of dDAVP are largely independent of PI3K signaling. The V2 receptor antagonist SR121463 completely abolished the antiapoptotic effects of dDAVP. In addition, incubation with 8-cpt-cAMP, a cell-permeable analog of cAMP, reproduced the antiapoptotic effects of dDAVP. Both dDAVP and 8-cpt-cAMP increased phosphorylation of proapoptotic Bcl-2 family members Bad and Bok. Bad phosphorylation at Ser-112 and Ser-155 is known to inhibit its proapoptotic activity. Preincubation with H89 blocked dDAVP-induced phosphorylation of both Bad and Bok, suggesting dependence on protein kinase A (PKA). This study provides evidence that AVP can inhibit apoptosis through the V2 receptor and downstream cAMP-mediated pathways in mammalian kidney. The antiapoptotic action of AVP may be relevant to a number of physiological and pathophysiological conditions including osmotic tolerance in the inner medulla, escape from AVP-induced antidiuresis, and polycystic kidney disease.</jats:p> Vasopressin inhibits apoptosis in renal collecting duct cells American Journal of Physiology-Renal Physiology
spellingShingle Miller, R. Lance, Sandoval, Pablo C., Pisitkun, Trairak, Knepper, Mark A., Hoffert, Jason D., American Journal of Physiology-Renal Physiology, Vasopressin inhibits apoptosis in renal collecting duct cells, Physiology
title Vasopressin inhibits apoptosis in renal collecting duct cells
title_full Vasopressin inhibits apoptosis in renal collecting duct cells
title_fullStr Vasopressin inhibits apoptosis in renal collecting duct cells
title_full_unstemmed Vasopressin inhibits apoptosis in renal collecting duct cells
title_short Vasopressin inhibits apoptosis in renal collecting duct cells
title_sort vasopressin inhibits apoptosis in renal collecting duct cells
title_unstemmed Vasopressin inhibits apoptosis in renal collecting duct cells
topic Physiology
url http://dx.doi.org/10.1152/ajprenal.00431.2012