Effect of tibolone pretreatment on kinases and phosphatases that regulate the expression and phosphorylation of Tau in the hippocampus of rats exposed to ozone

Rodolfo Pinto-Almazán, Julia J. Segura-Uribe, Marvin A. Soriano-Ursúa, Eunice D. Farfán-García, Juan M. Gallardo, Christian Guerra-Araiza

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Oxidative stress (OS) is a key process in the development of many neurodegenerative diseases, memory disorders, and other pathological processes related to aging. Tibolone (TIB), a synthetic hormone used as a treatment for menopausal symptoms, decreases lipoperoxidation levels, prevents memory impairment and learning disability caused by ozone (O3) exposure. However, it is not clear if TIB could prevent the increase in phosphorylation induced by oxidative stress of the microtubule-associated protein Tau. In this study, the effects of TIB at different times of administration on the phosphorylation of Tau, the activation of glycogen synthase kinase-3β (GSK3β), and the inactivation of Akt and phosphatases PP2A and PTEN induced by O3 exposure were assessed in adult male Wistar rats. Rats were divided into 10 groups: Control group (ozone-free air plus vehicle [C]), control + TIB group (ozone-free air plus TIB 1 mg/kg [C + TIB]); 7, 15, 30, and 60 days of ozone exposure groups [O3] and 7, 15, 30, and 60 days of TIB 1 mg/kg before ozone exposure groups [O3 + TIB]. The effects of O3 exposure and TIB administration were assessed by western blot analysis of total and phosphorylated Tau, GSK3β, Akt, PP2A, and PTEN proteins and oxidative stress marker nitrotyrosine, and superoxide dismutase activity and lipid peroxidation of malondialdehyde by two different spectrophotometric methods (Marklund and TBARS, respectively). We observed that O3 exposure increases Tau phosphorylation, which is correlated with decreased PP2A and PTEN protein levels, diminished Akt protein levels, and increased GSK3β protein levels in the hippocampus of adult male rats. The effects of O3 exposure were prevented by the long-term treatment (over 15 days) with TIB. Malondialdehyde and nitrotyrosine levels increased from 15 to 60 days of exposure to O3 in comparison to C group, and superoxide dismutase activity decreased. Furthermore, TIB administration limited the changes induced by O3 exposure. Our results suggest a beneficial use of hormone replacement therapy with TIB to prevent neurodegeneration caused by O3 exposure in rats.

Original languageEnglish
Pages (from-to)440-448
Number of pages9
JournalNeural Regeneration Research
Volume13
Issue number3
DOIs
StatePublished - Mar 2018

Fingerprint

tibolone
Ozone
Phosphoric Monoester Hydrolases
Hippocampus
Phosphotransferases
Phosphorylation
PTEN Phosphohydrolase
Glycogen Synthase Kinase 3
Oxidative Stress
Malondialdehyde
Superoxide Dismutase
Air

Keywords

  • GSK3
  • Hippocampus
  • Neuroprotection
  • Oxidative stress
  • Ozone exposure
  • Tau
  • Tibolone

Cite this

@article{842f6070922d476693d06f9a3684375a,
title = "Effect of tibolone pretreatment on kinases and phosphatases that regulate the expression and phosphorylation of Tau in the hippocampus of rats exposed to ozone",
abstract = "Oxidative stress (OS) is a key process in the development of many neurodegenerative diseases, memory disorders, and other pathological processes related to aging. Tibolone (TIB), a synthetic hormone used as a treatment for menopausal symptoms, decreases lipoperoxidation levels, prevents memory impairment and learning disability caused by ozone (O3) exposure. However, it is not clear if TIB could prevent the increase in phosphorylation induced by oxidative stress of the microtubule-associated protein Tau. In this study, the effects of TIB at different times of administration on the phosphorylation of Tau, the activation of glycogen synthase kinase-3β (GSK3β), and the inactivation of Akt and phosphatases PP2A and PTEN induced by O3 exposure were assessed in adult male Wistar rats. Rats were divided into 10 groups: Control group (ozone-free air plus vehicle [C]), control + TIB group (ozone-free air plus TIB 1 mg/kg [C + TIB]); 7, 15, 30, and 60 days of ozone exposure groups [O3] and 7, 15, 30, and 60 days of TIB 1 mg/kg before ozone exposure groups [O3 + TIB]. The effects of O3 exposure and TIB administration were assessed by western blot analysis of total and phosphorylated Tau, GSK3β, Akt, PP2A, and PTEN proteins and oxidative stress marker nitrotyrosine, and superoxide dismutase activity and lipid peroxidation of malondialdehyde by two different spectrophotometric methods (Marklund and TBARS, respectively). We observed that O3 exposure increases Tau phosphorylation, which is correlated with decreased PP2A and PTEN protein levels, diminished Akt protein levels, and increased GSK3β protein levels in the hippocampus of adult male rats. The effects of O3 exposure were prevented by the long-term treatment (over 15 days) with TIB. Malondialdehyde and nitrotyrosine levels increased from 15 to 60 days of exposure to O3 in comparison to C group, and superoxide dismutase activity decreased. Furthermore, TIB administration limited the changes induced by O3 exposure. Our results suggest a beneficial use of hormone replacement therapy with TIB to prevent neurodegeneration caused by O3 exposure in rats.",
keywords = "GSK3, Hippocampus, Neuroprotection, Oxidative stress, Ozone exposure, Tau, Tibolone",
author = "Rodolfo Pinto-Almaz{\'a}n and Segura-Uribe, {Julia J.} and Soriano-Urs{\'u}a, {Marvin A.} and Farf{\'a}n-Garc{\'i}a, {Eunice D.} and Gallardo, {Juan M.} and Christian Guerra-Araiza",
year = "2018",
month = "3",
doi = "10.4103/1673-5374.228726",
language = "Ingl{\'e}s",
volume = "13",
pages = "440--448",
journal = "Neural Regeneration Research",
issn = "1673-5374",
publisher = "Wolters Kluwer Medknow Publications",
number = "3",

}

Effect of tibolone pretreatment on kinases and phosphatases that regulate the expression and phosphorylation of Tau in the hippocampus of rats exposed to ozone. / Pinto-Almazán, Rodolfo; Segura-Uribe, Julia J.; Soriano-Ursúa, Marvin A.; Farfán-García, Eunice D.; Gallardo, Juan M.; Guerra-Araiza, Christian.

In: Neural Regeneration Research, Vol. 13, No. 3, 03.2018, p. 440-448.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of tibolone pretreatment on kinases and phosphatases that regulate the expression and phosphorylation of Tau in the hippocampus of rats exposed to ozone

AU - Pinto-Almazán, Rodolfo

AU - Segura-Uribe, Julia J.

AU - Soriano-Ursúa, Marvin A.

AU - Farfán-García, Eunice D.

AU - Gallardo, Juan M.

AU - Guerra-Araiza, Christian

PY - 2018/3

Y1 - 2018/3

N2 - Oxidative stress (OS) is a key process in the development of many neurodegenerative diseases, memory disorders, and other pathological processes related to aging. Tibolone (TIB), a synthetic hormone used as a treatment for menopausal symptoms, decreases lipoperoxidation levels, prevents memory impairment and learning disability caused by ozone (O3) exposure. However, it is not clear if TIB could prevent the increase in phosphorylation induced by oxidative stress of the microtubule-associated protein Tau. In this study, the effects of TIB at different times of administration on the phosphorylation of Tau, the activation of glycogen synthase kinase-3β (GSK3β), and the inactivation of Akt and phosphatases PP2A and PTEN induced by O3 exposure were assessed in adult male Wistar rats. Rats were divided into 10 groups: Control group (ozone-free air plus vehicle [C]), control + TIB group (ozone-free air plus TIB 1 mg/kg [C + TIB]); 7, 15, 30, and 60 days of ozone exposure groups [O3] and 7, 15, 30, and 60 days of TIB 1 mg/kg before ozone exposure groups [O3 + TIB]. The effects of O3 exposure and TIB administration were assessed by western blot analysis of total and phosphorylated Tau, GSK3β, Akt, PP2A, and PTEN proteins and oxidative stress marker nitrotyrosine, and superoxide dismutase activity and lipid peroxidation of malondialdehyde by two different spectrophotometric methods (Marklund and TBARS, respectively). We observed that O3 exposure increases Tau phosphorylation, which is correlated with decreased PP2A and PTEN protein levels, diminished Akt protein levels, and increased GSK3β protein levels in the hippocampus of adult male rats. The effects of O3 exposure were prevented by the long-term treatment (over 15 days) with TIB. Malondialdehyde and nitrotyrosine levels increased from 15 to 60 days of exposure to O3 in comparison to C group, and superoxide dismutase activity decreased. Furthermore, TIB administration limited the changes induced by O3 exposure. Our results suggest a beneficial use of hormone replacement therapy with TIB to prevent neurodegeneration caused by O3 exposure in rats.

AB - Oxidative stress (OS) is a key process in the development of many neurodegenerative diseases, memory disorders, and other pathological processes related to aging. Tibolone (TIB), a synthetic hormone used as a treatment for menopausal symptoms, decreases lipoperoxidation levels, prevents memory impairment and learning disability caused by ozone (O3) exposure. However, it is not clear if TIB could prevent the increase in phosphorylation induced by oxidative stress of the microtubule-associated protein Tau. In this study, the effects of TIB at different times of administration on the phosphorylation of Tau, the activation of glycogen synthase kinase-3β (GSK3β), and the inactivation of Akt and phosphatases PP2A and PTEN induced by O3 exposure were assessed in adult male Wistar rats. Rats were divided into 10 groups: Control group (ozone-free air plus vehicle [C]), control + TIB group (ozone-free air plus TIB 1 mg/kg [C + TIB]); 7, 15, 30, and 60 days of ozone exposure groups [O3] and 7, 15, 30, and 60 days of TIB 1 mg/kg before ozone exposure groups [O3 + TIB]. The effects of O3 exposure and TIB administration were assessed by western blot analysis of total and phosphorylated Tau, GSK3β, Akt, PP2A, and PTEN proteins and oxidative stress marker nitrotyrosine, and superoxide dismutase activity and lipid peroxidation of malondialdehyde by two different spectrophotometric methods (Marklund and TBARS, respectively). We observed that O3 exposure increases Tau phosphorylation, which is correlated with decreased PP2A and PTEN protein levels, diminished Akt protein levels, and increased GSK3β protein levels in the hippocampus of adult male rats. The effects of O3 exposure were prevented by the long-term treatment (over 15 days) with TIB. Malondialdehyde and nitrotyrosine levels increased from 15 to 60 days of exposure to O3 in comparison to C group, and superoxide dismutase activity decreased. Furthermore, TIB administration limited the changes induced by O3 exposure. Our results suggest a beneficial use of hormone replacement therapy with TIB to prevent neurodegeneration caused by O3 exposure in rats.

KW - GSK3

KW - Hippocampus

KW - Neuroprotection

KW - Oxidative stress

KW - Ozone exposure

KW - Tau

KW - Tibolone

UR - http://www.scopus.com/inward/record.url?scp=85051988007&partnerID=8YFLogxK

U2 - 10.4103/1673-5374.228726

DO - 10.4103/1673-5374.228726

M3 - Artículo

C2 - 29623928

AN - SCOPUS:85051988007

VL - 13

SP - 440

EP - 448

JO - Neural Regeneration Research

JF - Neural Regeneration Research

SN - 1673-5374

IS - 3

ER -