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Expression of stress-activated kinases c-Jun N-terminal kinase (SAPK/JNK-P) and p38 kinase (p38-P), and tau hyperphosphorylation in neurites surrounding betaA plaques in APP Tg2576 mice.
Neuropathol Appl Neurobiol 2004; 30(5):491-502NA

Abstract

Hyperphosphorylated tau in neurites surrounding beta-amyloid (betaA) deposits, as revealed with phospho-specific anti-tau antibodies, are found in amyloid precursor protein (APP) Tg2576 mice. Because betaA is a source of oxidative stress and may be toxic for cultured cells, the present study examines the expression of phosphorylated (active) stress-activated kinase c-Jun N-terminal kinase (SAPK/JNK-P) and p38 kinase (p38-P), which have the capacity to phosphorylate tau at specific sites, and their specific substrates c-Jun and ATF-2, which are involved in cell death and survival in several paradigms, in Tg2576 mice. The study was planned to shed light about the involvement of these kinases in tau phosphorylation in cell processes surrounding amyloid plaques, as well as in the possible phosphorylation (activation) of c-Jun and activating transcription factor-2 (ATF-2) in relation to betaA deposition. Moderate increase in the expression of phosphorylated mitogen-activated protein kinase and extracelullar signal-regulated kinase (MAPK/ERK-P) occurs in a few amyloid plaques. However, strong expression of SAPK/JNK-P and p38-P is found in the majority of, if not all, amyloid plaques, as seen in serial consecutive sections stained for betaA and stress kinases. Moreover, confocal microscopy reveals colocalization of phospho-tau and SAPK/JNK-P, and phospho-tau and p38-P in many dystrophic neurites surrounding amyloid plaques. Increased expression levels of nonbound tau, SAPK/JNK-P and p38-P are corroborated by Western blots of total cortical homogenate supernatants in Tg2576 mice when compared with age-matched controls. No increase in phosphorylated c-JunSer63 (c-Jun-P) and ATF-2Thr71 (ATF-2-P) is found in association with betaA deposits. In addition, no expression of active (cleaved) caspase-3 (17 kDa) has been found in transgenic mice. Taken together, these observations provide a link between betaA-induced oxidative stress, activation of stress kinases SAPK/JNK and p38, and tau hyperphosphorylation in neurites surrounding amyloid plaques, but activation of these kinases is not associated with accumulation of c-Jun-P and ATF-2-P, nor with activation of active caspase-3 in the vicinity of betaA deposits.

Authors+Show Affiliations

Institut de Neuropatologia, Servei Anatomia Patològica, Hospital de Bellvitge, Hospitalet de Llobregat, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15488025

Citation

Puig, B, et al. "Expression of Stress-activated Kinases c-Jun N-terminal Kinase (SAPK/JNK-P) and P38 Kinase (p38-P), and Tau Hyperphosphorylation in Neurites Surrounding betaA Plaques in APP Tg2576 Mice." Neuropathology and Applied Neurobiology, vol. 30, no. 5, 2004, pp. 491-502.
Puig B, Gómez-Isla T, Ribé E, et al. Expression of stress-activated kinases c-Jun N-terminal kinase (SAPK/JNK-P) and p38 kinase (p38-P), and tau hyperphosphorylation in neurites surrounding betaA plaques in APP Tg2576 mice. Neuropathol Appl Neurobiol. 2004;30(5):491-502.
Puig, B., Gómez-Isla, T., Ribé, E., Cuadrado, M., Torrejón-Escribano, B., Dalfó, E., & Ferrer, I. (2004). Expression of stress-activated kinases c-Jun N-terminal kinase (SAPK/JNK-P) and p38 kinase (p38-P), and tau hyperphosphorylation in neurites surrounding betaA plaques in APP Tg2576 mice. Neuropathology and Applied Neurobiology, 30(5), pp. 491-502.
Puig B, et al. Expression of Stress-activated Kinases c-Jun N-terminal Kinase (SAPK/JNK-P) and P38 Kinase (p38-P), and Tau Hyperphosphorylation in Neurites Surrounding betaA Plaques in APP Tg2576 Mice. Neuropathol Appl Neurobiol. 2004;30(5):491-502. PubMed PMID: 15488025.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of stress-activated kinases c-Jun N-terminal kinase (SAPK/JNK-P) and p38 kinase (p38-P), and tau hyperphosphorylation in neurites surrounding betaA plaques in APP Tg2576 mice. AU - Puig,B, AU - Gómez-Isla,T, AU - Ribé,E, AU - Cuadrado,M, AU - Torrejón-Escribano,B, AU - Dalfó,E, AU - Ferrer,I, PY - 2004/10/19/pubmed PY - 2004/12/16/medline PY - 2004/10/19/entrez SP - 491 EP - 502 JF - Neuropathology and applied neurobiology JO - Neuropathol. Appl. Neurobiol. VL - 30 IS - 5 N2 - Hyperphosphorylated tau in neurites surrounding beta-amyloid (betaA) deposits, as revealed with phospho-specific anti-tau antibodies, are found in amyloid precursor protein (APP) Tg2576 mice. Because betaA is a source of oxidative stress and may be toxic for cultured cells, the present study examines the expression of phosphorylated (active) stress-activated kinase c-Jun N-terminal kinase (SAPK/JNK-P) and p38 kinase (p38-P), which have the capacity to phosphorylate tau at specific sites, and their specific substrates c-Jun and ATF-2, which are involved in cell death and survival in several paradigms, in Tg2576 mice. The study was planned to shed light about the involvement of these kinases in tau phosphorylation in cell processes surrounding amyloid plaques, as well as in the possible phosphorylation (activation) of c-Jun and activating transcription factor-2 (ATF-2) in relation to betaA deposition. Moderate increase in the expression of phosphorylated mitogen-activated protein kinase and extracelullar signal-regulated kinase (MAPK/ERK-P) occurs in a few amyloid plaques. However, strong expression of SAPK/JNK-P and p38-P is found in the majority of, if not all, amyloid plaques, as seen in serial consecutive sections stained for betaA and stress kinases. Moreover, confocal microscopy reveals colocalization of phospho-tau and SAPK/JNK-P, and phospho-tau and p38-P in many dystrophic neurites surrounding amyloid plaques. Increased expression levels of nonbound tau, SAPK/JNK-P and p38-P are corroborated by Western blots of total cortical homogenate supernatants in Tg2576 mice when compared with age-matched controls. No increase in phosphorylated c-JunSer63 (c-Jun-P) and ATF-2Thr71 (ATF-2-P) is found in association with betaA deposits. In addition, no expression of active (cleaved) caspase-3 (17 kDa) has been found in transgenic mice. Taken together, these observations provide a link between betaA-induced oxidative stress, activation of stress kinases SAPK/JNK and p38, and tau hyperphosphorylation in neurites surrounding amyloid plaques, but activation of these kinases is not associated with accumulation of c-Jun-P and ATF-2-P, nor with activation of active caspase-3 in the vicinity of betaA deposits. SN - 0305-1846 UR - https://www.unboundmedicine.com/medline/citation/15488025/Expression_of_stress_activated_kinases_c_Jun_N_terminal_kinase__SAPK/JNK_P__and_p38_kinase__p38_P__and_tau_hyperphosphorylation_in_neurites_surrounding_betaA_plaques_in_APP_Tg2576_mice_ L2 - https://doi.org/10.1111/j.1365-2990.2004.00569.x DB - PRIME DP - Unbound Medicine ER -