The Catalytic Subunit of Telomerase is Expressed in Developing Brain Neurons and Serves a Cell Survival-promoting Function

Overview

Journal J Mol Neurosci

Specialties Molecular Biology
Neurology

Date 2000 Jun 15

PMID 10854032

Citations 50

Authors

W Fu

M Killen

C Culmsee

S Dhar

T K Pandita

M P Mattson

Affiliations

Soon will be listed here.

Abstract

Telomerase, a specialized reverse transcriptase (RT) linked to cell immortalization and cancer, has been thought not to be expressed in postmitotic cells. We now report that telomerase activity and its essential catalytic subunit, telomerase reverse transcriptase (TERT), are expressed in neurons in the brains of rodents during embryonic and early postnatal development, and are subsequently downregulated. Suppression of TERT expression in cultured embryonic hippocampal neurons increases their vulnerability to apoptosis and excitotoxicity. Overexpression of TERT in PC12 cells suppresses apoptosis induced by trophic factor withdrawal. TERT exerts its anti-apoptotic action at an early stage of the cell death process prior to mitochondrial dysfunction and caspase activation. TERT may serve a neuron survival-promoting function in the developing brain, and downregulation of TERT in the adult brain may contribute to increased neuronal vulnerability in various age-related neurodegenerative disorders.

Citing Articles

TERT mediates the U-shape of glucocorticoids effects in modulation of hippocampal neural stem cells and associated brain function.

Liu M, Fan Y, Ni N, Yu T, Mao Z, Huang H CNS Neurosci Ther. 2024; 30(2):e14577.

PMID: 38421107 PMC: 10850922. DOI: 10.1111/cns.14577.

Ageing in the brain: mechanisms and rejuvenating strategies.

Gaspar-Silva F, Trigo D, Magalhaes J Cell Mol Life Sci. 2023; 80(7):190.

PMID: 37354261 PMC: 10290611. DOI: 10.1007/s00018-023-04832-6.

Multiple Actions of Telomerase Reverse Transcriptase in Cell Death Regulation.

Palamarchuk A, Kovalenko E, Streltsova M Biomedicines. 2023; 11(4).

PMID: 37189709 PMC: 10136030. DOI: 10.3390/biomedicines11041091.

The neuro-protective role of telomerase via TERT/TERF-2 in the acute phase of spinal cord injury.

Chang D, Kim J, Kim H, Kim Y, Kim S, Ha K Eur Spine J. 2023; 32(7):2431-2440.

PMID: 37165116 DOI: 10.1007/s00586-023-07561-3.

Cellular Senescence as a Brake or Accelerator for Oncogenic Transformation and Role in Lymphatic Metastasis.

Banerjee P, Gaddam N, Pandita T, Chakraborty S Int J Mol Sci. 2023; 24(3).

PMID: 36769195 PMC: 9917379. DOI: 10.3390/ijms24032877.

References

Chin L, Artandi S, Shen Q, Tam A, Lee S, Gottlieb G . p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell. 1999; 97(4):527-38. DOI: 10.1016/s0092-8674(00)80762-x. View

Wright W, Piatyszek M, Rainey W, Byrd W, Shay J . Telomerase activity in human germline and embryonic tissues and cells. Dev Genet. 1996; 18(2):173-9. DOI: 10.1002/(SICI)1520-6408(1996)18:2<173::AID-DVG10>3.0.CO;2-3. View

Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T . p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science. 1999; 283(5406):1321-5. DOI: 10.1126/science.283.5406.1321. View

Pandita T, Hall E, Hei T, Piatyszek M, Wright W, Piao C . Chromosome end-to-end associations and telomerase activity during cancer progression in human cells after treatment with alpha-particles simulating radon progeny. Oncogene. 1996; 13(7):1423-30. View

Zhu J, Wang H, Bishop J, Blackburn E . Telomerase extends the lifespan of virus-transformed human cells without net telomere lengthening. Proc Natl Acad Sci U S A. 1999; 96(7):3723-8. PMC: 22361. DOI: 10.1073/pnas.96.7.3723. View

Blasco M, Funk W, Villeponteau B, Greider C . Functional characterization and developmental regulation of mouse telomerase RNA. Science. 1995; 269(5228):1267-70. DOI: 10.1126/science.7544492. View

Dirnagl U, Iadecola C, Moskowitz M . Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 1999; 22(9):391-7. DOI: 10.1016/s0166-2236(99)01401-0. View

Kondo S, Tanaka Y, Kondo Y, Hitomi M, Barnett G, Ishizaka Y . Antisense telomerase treatment: induction of two distinct pathways, apoptosis and differentiation. FASEB J. 1998; 12(10):801-11. DOI: 10.1096/fasebj.12.10.801. View

Mattson M, Dou P, Kater S . Outgrowth-regulating actions of glutamate in isolated hippocampal pyramidal neurons. J Neurosci. 1988; 8(6):2087-100. PMC: 6569320. View

10.

Greenberg R, Allsopp R, Chin L, Morin G, DePinho R . Expression of mouse telomerase reverse transcriptase during development, differentiation and proliferation. Oncogene. 1998; 16(13):1723-30. DOI: 10.1038/sj.onc.1201933. View

11.

Vaziri H, Benchimol S . Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span. Curr Biol. 1998; 8(5):279-82. DOI: 10.1016/s0960-9822(98)70109-5. View

12.

Pandita T, Benvenuto J, Shay J, Pandita R, Rakovitch E, Geard C . Effect of penclomedine (NSC-338720) on telomere fusions, chromatin blebbing, and cell viability with and without telomerase activity and abrogated p53 function. Biochem Pharmacol. 1997; 53(3):409-15. DOI: 10.1016/s0006-2952(96)00766-6. View

13.

Kim N, Piatyszek M, Prowse K, Harley C, WEST M, Ho P . Specific association of human telomerase activity with immortal cells and cancer. Science. 1994; 266(5193):2011-5. DOI: 10.1126/science.7605428. View

14.

Sharma H, Sokoloski J, Perez J, Maltese J, Sartorelli A, Stein C . Differentiation of immortal cells inhibits telomerase activity. Proc Natl Acad Sci U S A. 1995; 92(26):12343-6. PMC: 40353. DOI: 10.1073/pnas.92.26.12343. View

15.

Fu W, Begley J, Killen M, Mattson M . Anti-apoptotic role of telomerase in pheochromocytoma cells. J Biol Chem. 1999; 274(11):7264-71. DOI: 10.1074/jbc.274.11.7264. View

16.

Vaziri H, Squire J, Pandita T, Bradley G, Kuba R, Zhang H . Analysis of genomic integrity and p53-dependent G1 checkpoint in telomerase-induced extended-life-span human fibroblasts. Mol Cell Biol. 1999; 19(3):2373-9. PMC: 84029. DOI: 10.1128/MCB.19.3.2373. View

17.

Furukawa K, Fu W, Li Y, Witke W, Kwiatkowski D, Mattson M . The actin-severing protein gelsolin modulates calcium channel and NMDA receptor activities and vulnerability to excitotoxicity in hippocampal neurons. J Neurosci. 1997; 17(21):8178-86. PMC: 6573728. View

18.

Cotman C . Apoptosis decision cascades and neuronal degeneration in Alzheimer's disease. Neurobiol Aging. 1998; 19(1 Suppl):S29-32. DOI: 10.1016/s0197-4580(98)00042-6. View

19.

Mattson M, Keller J, Begley J . Evidence for synaptic apoptosis. Exp Neurol. 1998; 153(1):35-48. DOI: 10.1006/exnr.1998.6863. View

20.

Guo Q, Fu W, Xie J, Luo H, Sells S, Geddes J . Par-4 is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer disease. Nat Med. 1998; 4(8):957-62. DOI: 10.1038/nm0898-957. View