Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

HCN Channel Activity Balances Quiescence and Proliferation in Neural Stem Cells and Is a Selective Target for Neuroprotection During Cancer Treatment

H. Johard, A. Omelyanenko, G. Fei, M. Zilberter, Z. Dave, R. Abu-Youssef, L. Schmidt, A. Harisankar, CT. Vincent, J. Walfridsson, S. Nelander, T. Harkany, K. Blomgren, M. Andäng

. 2020 ; 18 (10) : 1522-1533. [pub] 20200714

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc21026537

Children suffering from neurologic cancers undergoing chemotherapy and radiotherapy are at high risk of reduced neurocognitive abilities likely via damage to proliferating neural stem cells (NSC). Therefore, strategies to protect NSCs are needed. We argue that induced cell-cycle arrest/quiescence in NSCs during cancer treatment can represent such a strategy. Here, we show that hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels are dynamically expressed over the cell cycle in NSCs, depolarize the membrane potential, underlie spontaneous calcium oscillations and are required to maintain NSCs in the actively proliferating pool. Hyperpolarizing pharmacologic inhibition of HCN channels during exposure to ionizing radiation protects NSCs cells in neurogenic brain regions of young mice. In contrast, brain tumor-initiating cells, which also express HCN channels, remain proliferative during HCN inhibition. IMPLICATIONS: Our finding that NSCs can be selectively rescued while cancer cells remain sensitive to the treatment, provide a foundation for reduction of cognitive impairment in children with neurologic cancers.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc21026537
003      
CZ-PrNML
005      
20211026132824.0
007      
ta
008      
211013s2020 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1158/1541-7786.MCR-20-0292 $2 doi
035    __
$a (PubMed)32665429
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Johard, Helena $u Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden $u Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic
245    10
$a HCN Channel Activity Balances Quiescence and Proliferation in Neural Stem Cells and Is a Selective Target for Neuroprotection During Cancer Treatment / $c H. Johard, A. Omelyanenko, G. Fei, M. Zilberter, Z. Dave, R. Abu-Youssef, L. Schmidt, A. Harisankar, CT. Vincent, J. Walfridsson, S. Nelander, T. Harkany, K. Blomgren, M. Andäng
520    9_
$a Children suffering from neurologic cancers undergoing chemotherapy and radiotherapy are at high risk of reduced neurocognitive abilities likely via damage to proliferating neural stem cells (NSC). Therefore, strategies to protect NSCs are needed. We argue that induced cell-cycle arrest/quiescence in NSCs during cancer treatment can represent such a strategy. Here, we show that hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels are dynamically expressed over the cell cycle in NSCs, depolarize the membrane potential, underlie spontaneous calcium oscillations and are required to maintain NSCs in the actively proliferating pool. Hyperpolarizing pharmacologic inhibition of HCN channels during exposure to ionizing radiation protects NSCs cells in neurogenic brain regions of young mice. In contrast, brain tumor-initiating cells, which also express HCN channels, remain proliferative during HCN inhibition. IMPLICATIONS: Our finding that NSCs can be selectively rescued while cancer cells remain sensitive to the treatment, provide a foundation for reduction of cognitive impairment in children with neurologic cancers.
650    _2
$a zvířata $7 D000818
650    _2
$a proliferace buněk $7 D049109
650    _2
$a lidé $7 D006801
650    _2
$a hyperpolarizační iontové kanály řízené cyklickými nukleotidy $x metabolismus $7 D064428
650    _2
$a myši $7 D051379
650    _2
$a nádory $x farmakoterapie $7 D009369
650    _2
$a nervové kmenové buňky $x metabolismus $7 D058953
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Omelyanenko, Anna $u Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
700    1_
$a Fei, Gao $u Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden $u College of Veterinary Medicine, Jilin University, Changchun, Jilin, China
700    1_
$a Zilberter, Misha $u Gladstone Institute of Neurological Disease, San Francisco, California
700    1_
$a Dave, Zankruti $u Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden
700    1_
$a Abu-Youssef, Randa $u Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
700    1_
$a Schmidt, Linnéa $u Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden
700    1_
$a Harisankar, Aditya $u Department of Medicine, Karolinska Institutet, Huddinge, Sweden
700    1_
$a Vincent, C Theresa $u Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden $u Department of Microbiology, New York University School of Medicine, New York, New York
700    1_
$a Walfridsson, Julian $u Department of Medicine, Karolinska Institutet, Huddinge, Sweden
700    1_
$a Nelander, Sven $u Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden
700    1_
$a Harkany, Tibor $u Department of Neuroscience, Karolinska Institutet, Solna, Sweden $u Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna, Austria
700    1_
$a Blomgren, Klas $u Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden $u Pediatric Oncology, Karolinska University Hospital, Stockholm, Sweden
700    1_
$a Andäng, Michael $u Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. michael.andang@igp.uu.se $u Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic
773    0_
$w MED00007101 $t Molecular cancer research : MCR $x 1557-3125 $g Roč. 18, č. 10 (2020), s. 1522-1533
856    41
$u https://pubmed.ncbi.nlm.nih.gov/32665429 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20211013 $b ABA008
991    __
$a 20211026132830 $b ABA008
999    __
$a ok $b bmc $g 1715304 $s 1147044
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2020 $b 18 $c 10 $d 1522-1533 $e 20200714 $i 1557-3125 $m Molecular cancer research $n Mol Cancer Res $x MED00007101
LZP    __
$a Pubmed-20211013

Najít záznam

Citační ukazatele

Pouze přihlášení uživatelé

Možnosti archivace