Gestational zinc deficiency impairs brain astrogliogenesis in rats through multistep alterations of the JAK/STAT3 signaling pathway
| Autor: | Adelaide C. Hellmers, Suangsuda Supasai, Patricia Andrea Mathieu, Regina C. Marino, Ana M. Adamo, Eleonora Cremonini, Patricia I. Oteiza |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Medicine (General) Clinical Biochemistry Reproductive health and childbirth Medical Biochemistry and Metabolomics Biochemistry Stat3 Signaling Pathway Rats Sprague-Dawley STAT3 0302 clinical medicine Ubiquitin Tubulin Biology (General) Pediatric biology Kinase Chemistry Tubulin oxidation Brain Pharmacology and Pharmaceutical Sciences Brain development Zinc medicine.anatomical_structure Neurological Research Paper Signal Transduction Astrocyte medicine.medical_specialty QH301-705.5 Offspring 1.1 Normal biological development and functioning Phosphatase 03 medical and health sciences R5-920 Underpinning research Internal medicine medicine Animals Nutrition Organic Chemistry Neurosciences medicine.disease Rats 030104 developmental biology Endocrinology Astrocytes biology.protein Zinc deficiency Sprague-Dawley Biochemistry and Cell Biology Astrogliogenesis 030217 neurology & neurosurgery |
| Zdroj: | Redox Biology, Vol 44, Iss, Pp 102017-(2021) Redox Biology |
| ISSN: | 2213-2317 |
| Popis: | We previously showed that zinc (Zn) deficiency affects the STAT3 signaling pathway in part through redox-regulated mechanisms. Given that STAT3 is central to the process of astrogliogenesis, this study investigated the consequences of maternal marginal Zn deficiency on the developmental timing and key mechanisms of STAT3 activation, and its consequences on astrogliogenesis in the offspring. This work characterized the temporal profile of cortical STAT3 activation from the mid embryonic stage up to young adulthood in the offspring from dams fed a marginal Zn deficient diet (MZD) throughout gestation and until postnatal day (P) 2. All rats were fed a Zn sufficient diet (control) from P2 until P56. Maternal zinc deficiency disrupted cortical STAT3 activation at E19 and P2. This was accompanied by altered activation of JAK2 kinase due to changes in PTP1B phosphatase activity. The underlying mechanisms mediating the adverse impact of a decreased Zn availability on STAT3 activation in the offspring brain include: (i) impaired PTP1B degradation via the ubiquitin/proteasome pathway; (ii) tubulin oxidation, associated decreased interactions with STAT3 and consequent impaired nuclear translocation; and (iii) decreased nuclear STAT3 acetylation. Zn deficiency-associated decreased STAT3 activation adversely impacted astrogliogenesis, leading to a lower astrocyte number in the early postnatal and adult brain cortex. Thus, a decreased availability of Zn during early development can have a major and irreversible adverse effect on astrogliogenesis, in part via multistep alterations in the STAT3 pathway. Graphical abstract Image 1 Highlights • Maternal zinc deficiency disrupts offspring's brain cortical STAT3 activation. • Impaired PTP1B proteasomal degradation inhibits JAK/STAT3 activation. • Tubulin oxidation and decreased interactions with STAT3 can affect STAT3's nuclear localization. • Zinc deficiency impairs STAT3 acetylation. • Altered STAT3 activation leads to astrogliogenesis disruption which extends into adulthood. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|