Estrogen attenuates ischemic oxidative damage via an estrogen receptor α-mediated inhibition of NADPH oxidase activation
Quanguang Zhang,Limor Raz,Ruimin Wang,Dong Han,Liesl De Sevilla,Fang Yang,Ratna K. Vadlamudi,Darrell W. Brann +7 more
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TLDR
In this paper, the authors reveal a novel extranuclear receptor-mediated antioxidant mechanism for E(2) during stroke, as well as a hypersensitivity of the CA3/CA4 region to ischemic injury after prolonged hypoestrogenicity.Abstract:
The goal of this study was to elucidate the mechanisms of 17beta-estradiol (E(2)) antioxidant and neuroprotective actions in stroke The results reveal a novel extranuclear receptor-mediated antioxidant mechanism for E(2) during stroke, as well as a hypersensitivity of the CA3/CA4 region to ischemic injury after prolonged hypoestrogenicity E(2) neuroprotection was shown to involve a profound attenuation of NADPH oxidase activation and superoxide production in hippocampal CA1 pyramidal neurons after stroke, an effect mediated by extranuclear estrogen receptor alpha (ERalpha)-mediated nongenomic signaling, involving Akt activation and subsequent phosphorylation/inactivation of Rac1, a factor critical for activation of NOX2 NADPH oxidase Intriguingly, E(2) nongenomic signaling, antioxidant action, and neuroprotection in the CA1 region were lost after long-term E(2) deprivation, and this loss was tissue specific because the uterus remained responsive to E(2) Correspondingly, a remarkable loss of ERalpha, but not ERbeta, was observed in the CA1 after long-term E(2) deprivation, with no change observed in the uterus As a whole, the study reveals a novel, membrane-mediated antioxidant mechanism in neurons by E(2) provides support and mechanistic insights for a "critical period" of E(2) replacement in the hippocampus and demonstrates a heretofore unknown hypersensitivity of the CA3/CA4 to ischemic injury after prolonged hypoestrogenicityread more
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Nox family NADPH oxidases: Molecular mechanisms of activation
TL;DR: It is concluded that the activity control of Nox enzymes is much more complex than anticipated and the development of "intelligent" Nox inhibitors plausible, which selectively attenuate disease-related Nox-mediated ROS formation without altering physiological signaling ROS is plausible.
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Evolution of NADPH Oxidase Inhibitors: Selectivity and Mechanisms for Target Engagement
Sebastian Altenhöfer,Kim A. Radermacher,Pamela W. M. Kleikers,Kirstin Wingler,Harald H.H.W. Schmidt +4 more
TL;DR: Whether novel NOX inhibitors enable reliable validation of NOX isoforms' pathological roles and whether this knowledge supports translation into pharmacological applications is discussed.
Journal ArticleDOI
The neuroprotective actions of oestradiol and oestrogen receptors
TL;DR: Recent discoveries have shown that oestradiol is not only a reproductive hormone but also a brain-derived neuroprotective factor in males and females and that ERs coordinate multiple signalling mechanisms that protect the brain from neurodegenerative diseases, affective disorders and cognitive decline.
Journal ArticleDOI
NADPH oxidase in brain injury and neurodegenerative disorders.
Merry W. Ma,Merry W. Ma,Jing Wang,Jing Wang,Quanguang Zhang,Quanguang Zhang,Ruimin Wang,Ruimin Wang,Krishnan M. Dhandapani,Krishnan M. Dhandapani,Ratna K. Vadlamudi,Darrell W. Brann,Darrell W. Brann +12 more
TL;DR: Evidence supporting the role of NADPH oxidase in the pathology of neurodegenerative disorders is summarized, pharmacological strategies of targeting this major oxidative stress pathway are explored, and obstacles that need to be overcome are outlined for successful translation of these therapies to the clinic.
Journal ArticleDOI
Estrogen, hormonal replacement therapy and cardiovascular disease.
TL;DR: HRT has become one of the most controversial topics related to women's health and future studies are necessary if to understand the divergent published findings regarding HRT and develop new therapeutic strategies to improve the quality of life for women.
References
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Journal ArticleDOI
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Karen Bedard,Karl-Heinz Krause +1 more
TL;DR: This review summarizes the current state of knowledge of the functions of NOX enzymes in physiology and pathology.
Journal ArticleDOI
Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial
Garnet L. Anderson,Marian C. Limacher,Annlouise R. Assaf,Tamsen Bassford,Shirley A.A. Beresford,Henry R. Black,Denise E. Bonds,Robert L. Brunner,Robert G. Brzyski,Bette J. Caan,Rowan T. Chlebowski,J. David Curb,Margery Gass,Jennifer Hays,Gerardo Heiss,Susan L. Hendrix,Barbara V. Howard,Judith Hsia,F. Allan Hubbell,Rebecca D. Jackson,Karen C. Johnson,Howard L. Judd,Jane Morley Kotchen,Lewis H. Kuller,Andrea Z. LaCroix,Dorothy S. Lane,Robert Langer,Norman L. Lasser,Cora E. Lewis,JoAnn E. Manson,Karen L. Margolis,Judith K. Ockene,Mary Jo O'Sullivan,Lawrence S. Phillips,Ross L. Prentice,Cheryl Ritenbaugh,John A Robbins,Jacques E. Rossouw,Gloria E. Sarto,Marcia L. Stefanick,Linda Van Horn,Jean Wactawski-Wende,Robert B. Wallace,Sylvia Wassertheil-Smoller +43 more
TL;DR: The use of conjugated equine estrogen (CEE) increases the risk of stroke, decreases therisk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years, indicating no overall benefit.
Journal ArticleDOI
A new model of bilateral hemispheric ischemia in the unanesthetized rat.
W A Pulsinelli,J B Brierley +1 more
TL;DR: A new model of transient, bilateral hemispheric ischemia in the unanesthetized rat is described, with the ease of preparation of large numbers of animals, a high rate of predictable ischemic neuronal damage, a low incidence of seizures and the absence of anesthesia.
Journal ArticleDOI
Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.
Sally A. Shumaker,Claudine Legault,Stephen R. Rapp,Leon J. Thal,Robert B. Wallace,Judith K. Ockene,Susan L. Hendrix,Beverly N. Jones,Annlouise R. Assaf,Rebecca D. Jackson,Jane Morley Kotchen,Sylvia Wassertheil-Smoller,Jean Wactawski-Wende +12 more
TL;DR: Estrogen plus progestin therapy increased the risk for probable dementia in postmenopausal women aged 65 years or older and did not prevent mild cognitive impairment in these women, supporting the conclusion that the risks of estrogen plus progESTin outweigh the benefits.
Journal ArticleDOI
Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase
Tommaso Simoncini,Ali Hafezi-Moghadam,Derek P. Brazil,Klaus Ley,William W. Chin,James K. Liao +5 more
TL;DR: It is shown that the ER isoform, ERα, binds in a ligand-dependent manner to the p85α regulatory subunit of phosphatidylinositol-3-OH kinase (PI(3)K).
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