Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis

Shrikant R Mulay; Jyaysi Desai; Santhosh V Kumar; Jonathan N Eberhard; Dana Thomasova; Simone Romoli; Melissa Grigorescu; Onkar P Kulkarni; Bastian Popper; Volker Vielhauer; Gabriele Zuchtriegel; Christoph Reichel; Jan Hinrich Bräsen; Paola Romagnani; Rostyslav Bilyy; Luis E Munoz; Martin Herrmann; Helen Liapis; Stefan Krautwald; Andreas Linkermann; Hans-Joachim Anders

doi:10.1038/ncomms10274

Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis

Standard

Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis. / Mulay, Shrikant R; Desai, Jyaysi; Kumar, Santhosh V; Eberhard, Jonathan N; Thomasova, Dana; Romoli, Simone; Grigorescu, Melissa; Kulkarni, Onkar P; Popper, Bastian; Vielhauer, Volker; Zuchtriegel, Gabriele; Reichel, Christoph; Bräsen, Jan Hinrich; Romagnani, Paola; Bilyy, Rostyslav; Munoz, Luis E; Herrmann, Martin; Liapis, Helen; Krautwald, Stefan; Linkermann, Andreas; Anders, Hans-Joachim.

In: NAT COMMUN, Vol. 7, 28.01.2016, p. 10274.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Mulay, SR, Desai, J, Kumar, SV, Eberhard, JN, Thomasova, D, Romoli, S, Grigorescu, M, Kulkarni, OP, Popper, B, Vielhauer, V, Zuchtriegel, G, Reichel, C, Bräsen, JH, Romagnani, P, Bilyy, R, Munoz, LE, Herrmann, M, Liapis, H, Krautwald, S, Linkermann, A & Anders, H-J 2016, 'Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis', NAT COMMUN, vol. 7, pp. 10274. https://doi.org/10.1038/ncomms10274

APA

Mulay, S. R., Desai, J., Kumar, S. V., Eberhard, J. N., Thomasova, D., Romoli, S., Grigorescu, M., Kulkarni, O. P., Popper, B., Vielhauer, V., Zuchtriegel, G., Reichel, C., Bräsen, J. H., Romagnani, P., Bilyy, R., Munoz, L. E., Herrmann, M., Liapis, H., Krautwald, S., ... Anders, H-J. (2016). Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis. NAT COMMUN, 7, 10274. https://doi.org/10.1038/ncomms10274

Vancouver

Mulay SR, Desai J, Kumar SV, Eberhard JN, Thomasova D, Romoli S et al. Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis. NAT COMMUN. 2016 Jan 28;7:10274. https://doi.org/10.1038/ncomms10274

Bibtex

@article{9548cbcb7815430d9e0a469155c366d7,

title = "Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis",

abstract = "Crystals cause injury in numerous disorders, and induce inflammation via the NLRP3 inflammasome, however, it remains unclear how crystals induce cell death. Here we report that crystals of calcium oxalate, monosodium urate, calcium pyrophosphate dihydrate and cystine trigger caspase-independent cell death in five different cell types, which is blocked by necrostatin-1. RNA interference for receptor-interacting protein kinase 3 (RIPK3) or mixed lineage kinase domain like (MLKL), two core proteins of the necroptosis pathway, blocks crystal cytotoxicity. Consistent with this, deficiency of RIPK3 or MLKL prevents oxalate crystal-induced acute kidney injury. The related tissue inflammation drives TNF-α-related necroptosis. Also in human oxalate crystal-related acute kidney injury, dying tubular cells stain positive for phosphorylated MLKL. Furthermore, necrostatin-1 and necrosulfonamide, an inhibitor for human MLKL suppress crystal-induced cell death in human renal progenitor cells. Together, TNF-α/TNFR1, RIPK1, RIPK3 and MLKL are molecular targets to limit crystal-induced cytotoxicity, tissue injury and organ failure.",

keywords = "Animals, Apoptosis, Calcium Oxalate, Calcium Pyrophosphate, Humans, Kidney Diseases, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Necrosis, Phosphorylation, Protein Kinases, Receptor-Interacting Protein Serine-Threonine Kinases, Tumor Necrosis Factor-alpha, Uric Acid, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",

author = "Mulay, {Shrikant R} and Jyaysi Desai and Kumar, {Santhosh V} and Eberhard, {Jonathan N} and Dana Thomasova and Simone Romoli and Melissa Grigorescu and Kulkarni, {Onkar P} and Bastian Popper and Volker Vielhauer and Gabriele Zuchtriegel and Christoph Reichel and Br{\"a}sen, {Jan Hinrich} and Paola Romagnani and Rostyslav Bilyy and Munoz, {Luis E} and Martin Herrmann and Helen Liapis and Stefan Krautwald and Andreas Linkermann and Hans-Joachim Anders",

year = "2016",

month = jan,

day = "28",

doi = "10.1038/ncomms10274",

language = "English",

volume = "7",

pages = "10274",

journal = "NAT COMMUN",

issn = "2041-1723",

publisher = "NATURE PUBLISHING GROUP",

}

RIS

TY - JOUR

T1 - Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis

AU - Mulay, Shrikant R

AU - Desai, Jyaysi

AU - Kumar, Santhosh V

AU - Eberhard, Jonathan N

AU - Thomasova, Dana

AU - Romoli, Simone

AU - Grigorescu, Melissa

AU - Kulkarni, Onkar P

AU - Popper, Bastian

AU - Vielhauer, Volker

AU - Zuchtriegel, Gabriele

AU - Reichel, Christoph

AU - Bräsen, Jan Hinrich

AU - Romagnani, Paola

AU - Bilyy, Rostyslav

AU - Munoz, Luis E

AU - Herrmann, Martin

AU - Liapis, Helen

AU - Krautwald, Stefan

AU - Linkermann, Andreas

AU - Anders, Hans-Joachim

PY - 2016/1/28

Y1 - 2016/1/28

N2 - Crystals cause injury in numerous disorders, and induce inflammation via the NLRP3 inflammasome, however, it remains unclear how crystals induce cell death. Here we report that crystals of calcium oxalate, monosodium urate, calcium pyrophosphate dihydrate and cystine trigger caspase-independent cell death in five different cell types, which is blocked by necrostatin-1. RNA interference for receptor-interacting protein kinase 3 (RIPK3) or mixed lineage kinase domain like (MLKL), two core proteins of the necroptosis pathway, blocks crystal cytotoxicity. Consistent with this, deficiency of RIPK3 or MLKL prevents oxalate crystal-induced acute kidney injury. The related tissue inflammation drives TNF-α-related necroptosis. Also in human oxalate crystal-related acute kidney injury, dying tubular cells stain positive for phosphorylated MLKL. Furthermore, necrostatin-1 and necrosulfonamide, an inhibitor for human MLKL suppress crystal-induced cell death in human renal progenitor cells. Together, TNF-α/TNFR1, RIPK1, RIPK3 and MLKL are molecular targets to limit crystal-induced cytotoxicity, tissue injury and organ failure.

AB - Crystals cause injury in numerous disorders, and induce inflammation via the NLRP3 inflammasome, however, it remains unclear how crystals induce cell death. Here we report that crystals of calcium oxalate, monosodium urate, calcium pyrophosphate dihydrate and cystine trigger caspase-independent cell death in five different cell types, which is blocked by necrostatin-1. RNA interference for receptor-interacting protein kinase 3 (RIPK3) or mixed lineage kinase domain like (MLKL), two core proteins of the necroptosis pathway, blocks crystal cytotoxicity. Consistent with this, deficiency of RIPK3 or MLKL prevents oxalate crystal-induced acute kidney injury. The related tissue inflammation drives TNF-α-related necroptosis. Also in human oxalate crystal-related acute kidney injury, dying tubular cells stain positive for phosphorylated MLKL. Furthermore, necrostatin-1 and necrosulfonamide, an inhibitor for human MLKL suppress crystal-induced cell death in human renal progenitor cells. Together, TNF-α/TNFR1, RIPK1, RIPK3 and MLKL are molecular targets to limit crystal-induced cytotoxicity, tissue injury and organ failure.

KW - Animals

KW - Apoptosis

KW - Calcium Oxalate

KW - Calcium Pyrophosphate

KW - Humans

KW - Kidney Diseases

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Necrosis

KW - Phosphorylation

KW - Protein Kinases

KW - Receptor-Interacting Protein Serine-Threonine Kinases

KW - Tumor Necrosis Factor-alpha

KW - Uric Acid

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/ncomms10274

DO - 10.1038/ncomms10274

M3 - SCORING: Journal article

C2 - 26817517

VL - 7

SP - 10274

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

ER -