Nicotine Alters Estrogen Receptor-Beta-Regulated Inflammasome Activity and Exacerbates Ischemic Brain Damage in Female Rats

d’Adesky, Nathan; Vaccari, Juan Pablo de Rivero; Bhattacharya, Pallab; Schatz, Marc; Pérez-Pinzón, Miguel A.; Bramlett, Helen M.; Raval, Ami P.

doi:10.3390/ijms19051330

Cited by 25 publications

(23 citation statements)

References 54 publications

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“…However, in this study it remained to be identified which subcellular location is responsible for ER-β’s inhibitory effect on inflammasomes [ 68 , 73 – 75 ]. Since nicotine reduces membrane-bound and mitochondrial ER-β availability and increases inflammasome activation and exacerbates post-ischemic damage in the brain of female rats, ER-β located at these two subcellular sites may be playing a role in regulation of inflammasome activation [ 35 ]. It is also likely that ER-β is translocated to cytoplasm following nicotine treatment, thus reducing the presence of ER-β at these subcellular locations and resulting in increased inflammasome activation.…”

Section: Menopausal Transition and Medical Comorbiditiesmentioning

confidence: 99%

“…Ultimately repeated or sustained activation of innate and adaptive immune responses can create the chronic low-grade inflammation typical of aging. The presence of the inflammasome complex in the cerebrospinal fluid of post-menopausal women suggests that the decline in estrogens induces a pro-inflammatory state [ 35 ]. Inflammasomes could be an important indicator of the effect of menopause on the immune system.…”

Section: Introductionmentioning

confidence: 99%

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The peri-menopause in a woman’s life: a systemic inflammatory phase that enables later neurodegenerative disease

McCarthy

Raval

2020

J Neuroinflammation

111

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The peri-menopause or menopausal transition—the time period that surrounds the final years of a woman’s reproductive life—is associated with profound reproductive and hormonal changes in a woman’s body and exponentially increases a woman’s risk of cerebral ischemia and Alzheimer’s disease. Although our understanding of the exact timeline or definition of peri-menopause is limited, it is clear that there are two stages to the peri-menopause. These are the early menopausal transition, where menstrual cycles are mostly regular, with relatively few interruptions, and the late transition, where amenorrhea becomes more prolonged and lasts for at least 60 days, up to the final menstrual period. Emerging evidence is showing that peri-menopause is pro-inflammatory and disrupts estrogen-regulated neurological systems. Estrogen is a master regulator that functions through a network of estrogen receptors subtypes alpha (ER-α) and beta (ER-β). Estrogen receptor-beta has been shown to regulate a key component of the innate immune response known as the inflammasome, and it also is involved in regulation of neuronal mitochondrial function. This review will present an overview of the menopausal transition as an inflammatory event, with associated systemic and central nervous system inflammation, plus regulation of the innate immune response by ER-β-mediated mechanisms.

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Section: Menopausal Transition and Medical Comorbiditiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The peri-menopause in a woman’s life: a systemic inflammatory phase that enables later neurodegenerative disease

McCarthy

Raval

2020

J Neuroinflammation

111

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“…In addition, ER-positive tumor tissues had preferentially higher α9-nAChR mRNA expression in comparison to ER-negative tumor tissues. Chronic nicotine treatment reduced the ERβ protein expression in brain hippocampus and cortical cells in female rats (d'Adesky et al, 2018;Raval et al, 2012). Further, intact ovaries or E2 supplementation increases the nicotine intake, thus promoting the rewarding effects of nicotine in female rats (Flores, Pipkin, Uribe, Perez, & O'Dell, 2016).…”

Section: Discussionmentioning

confidence: 92%

Structural binding perspectives of a major tobacco alkaloid, nicotine, and its metabolite cotinine with sex‐steroid nuclear receptors

Rehan

Ahmad²,

Beg

2020

J of Applied Toxicology

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Globally, more than a billion people smoke tobacco making it one of the biggest public health problems and a leading risk factor for global deaths. Nicotine, the main alkaloid in tobacco, has been shown to be associated with fertility problems in men and women. The adverse effects of tobacco/nicotine on reproduction have been attributed to deleterious effects on gametes, steroidogenic imbalance, and competitive inhibition of steroid receptors. The present study reports the sex‐steroid receptor disrupting potential of nicotine and its major metabolite cotinine against the estrogen receptor‐α (ERα), ERβ, androgen receptor (AR), and progesterone receptor (PR). Both ligands bound in the ligand‐binding pockets of ERα, ERβ, AR and PR and formed important hydrophobic interactions with different amino‐acid residues of receptors. Most of the residues of ERα, ERβ, AR and PR interacting with nicotine and cotinine were common with those of native/bound ligands of the receptors. Interacting amino acids most important for binding of nicotine and cotinine with each receptor were identified by loss in accessible surface area. Amino acids Leucine‐346, Leucine‐384 and Phenylalanine‐404 for ERα; Methionine‐336, Phenylalanine‐356 and Leucine‐298 for ERβ; and Leucine‐704 and Leucine‐718, respectively for AR and PR, were the most important residues for binding with nicotine and cotinine. Among the four receptors, based on the number of interactions, nicotine and cotinine had greater potential to interfere in the signaling of ERβ. In conclusion, the results suggested that nicotine and cotinine bind and interact with sex‐steroid nuclear receptors and have potential to interfere in the steroid hormone signaling resulting in reproductive dysfunction.

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“…From a primary culture approach, Kranc et al [ 14 ] analyze the expression profile of genes regulating steroid biosynthesis and metabolism in human ovarian granulosa cells. An in vivo study conducted by d’Adesky et al [ 15 ] indicates that nicotine modifies ER-β-regulated inflammasome activity and aggravates ischemic brain damage in female rats. The study conducted by Casanova-Nakayama et al [ 16 ] examines the immune-specific expression and estrogenic regulation of the four ER isoforms in female rainbow trout.…”

mentioning

confidence: 99%

Molecular Pathways of Estrogen Receptor Action

Pakdel

2018

IJMS

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Nicotine Alters Estrogen Receptor-Beta-Regulated Inflammasome Activity and Exacerbates Ischemic Brain Damage in Female Rats

Cited by 25 publications

References 54 publications

The peri-menopause in a woman’s life: a systemic inflammatory phase that enables later neurodegenerative disease

The peri-menopause in a woman’s life: a systemic inflammatory phase that enables later neurodegenerative disease

Structural binding perspectives of a major tobacco alkaloid, nicotine, and its metabolite cotinine with sex‐steroid nuclear receptors

Molecular Pathways of Estrogen Receptor Action

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