دورية أكاديمية
Sex-Specific Differences in Autophagic Responses to Experimental Ischemic Stroke.
العنوان: | Sex-Specific Differences in Autophagic Responses to Experimental Ischemic Stroke. |
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المؤلفون: | Patrizz AN; Department of Neurology, McGovern Medical School at the University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA., Moruno-Manchon JF; Department of Neurology, McGovern Medical School at the University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA., O'Keefe LM; Department of Neurology, Beth Israel Deaconess Hospital, 330 Brookline Avenue, Boston, MA 02215, USA., Doran SJ; Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA., Patel AR; Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA., Venna VR; Department of Neurology, McGovern Medical School at the University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA., Tsvetkov AS; Department of Neurology, McGovern Medical School at the University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA., Li J; Department of Neurology, McGovern Medical School at the University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA., McCullough LD; Department of Neurology, McGovern Medical School at the University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA. |
المصدر: | Cells [Cells] 2021 Jul 20; Vol. 10 (7). Date of Electronic Publication: 2021 Jul 20. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI |
مواضيع طبية MeSH: | Autophagy/*genetics , Beclin-1/*genetics , Brain Ischemia/*genetics , Ischemic Stroke/*genetics , Microtubule-Associated Proteins/*genetics , Neurons/*metabolism, Adenine/analogs & derivatives ; Adenine/pharmacology ; Animals ; Autophagy/drug effects ; Autophagy-Related Protein 7/genetics ; Autophagy-Related Protein 7/metabolism ; Autophagy-Related Protein-1 Homolog/genetics ; Autophagy-Related Protein-1 Homolog/metabolism ; Beclin-1/metabolism ; Brain Ischemia/metabolism ; Brain Ischemia/pathology ; Cell Hypoxia/genetics ; Cell Survival ; Female ; Gene Expression Regulation ; Glucose/deficiency ; Infarction, Middle Cerebral Artery/surgery ; Ischemic Stroke/metabolism ; Ischemic Stroke/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Microtubule-Associated Proteins/metabolism ; Neurons/pathology ; Ovariectomy/methods ; Sequestosome-1 Protein/genetics ; Sequestosome-1 Protein/metabolism ; Severity of Illness Index ; Sex Factors ; Signal Transduction |
مستخلص: | Ischemic stroke triggers a series of complex pathophysiological processes including autophagy. Differential activation of autophagy occurs in neurons derived from males versus females after stressors such as nutrient deprivation. Whether autophagy displays sexual dimorphism after ischemic stroke is unknown. We used a cerebral ischemia mouse model (middle cerebral artery occlusion, MCAO) to evaluate the effects of inhibiting autophagy in ischemic brain pathology. We observed that inhibiting autophagy reduced infarct volume in males and ovariectomized females. However, autophagy inhibition enhanced infarct size in females and in ovariectomized females supplemented with estrogen compared to control mice. We also observed that males had increased levels of Beclin1 and LC3 and decreased levels of pULK1 and p62 at 24 h, while females had decreased levels of Beclin1 and increased levels of ATG7. Furthermore, the levels of autophagy markers were increased under basal conditions and after oxygen and glucose deprivation in male neurons compared with female neurons in vitro. E2 supplementation significantly inhibited autophagy only in male neurons, and was beneficial for cell survival only in female neurons. This study shows that autophagy in the ischemic brain differs between the sexes, and that autophagy regulators have different effects in a sex-dependent manner in neurons. |
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معلومات مُعتمدة: | R01 NS103592 United States NS NINDS NIH HHS; R01 NS108779 United States NS NINDS NIH HHS; R01 NS055215 United States NS NINDS NIH HHS; TL1 TR000369 United States TR NCATS NIH HHS; R01 NS078446 United States NS NINDS NIH HHS |
فهرسة مساهمة: | Keywords: 3-methyladenine; autophagy; ischemic stroke; middle cerebral artery occlusion; neuroprotection; sex differences |
المشرفين على المادة: | 0 (Atg7 protein, mouse) 0 (Beclin-1) 0 (Becn1 protein, mouse) 0 (Map1lc3b protein, mouse) 0 (Microtubule-Associated Proteins) 0 (Sequestosome-1 Protein) 0 (Sqstm1 protein, mouse) 5142-23-4 (3-methyladenine) EC 2.7.11.1 (Autophagy-Related Protein-1 Homolog) EC 2.7.11.1 (Ulk1 protein, mouse) EC 6.2.1.45 (Autophagy-Related Protein 7) IY9XDZ35W2 (Glucose) JAC85A2161 (Adenine) |
تواريخ الأحداث: | Date Created: 20210807 Date Completed: 20211027 Latest Revision: 20220216 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC8304137 |
DOI: | 10.3390/cells10071825 |
PMID: | 34359998 |
قاعدة البيانات: | MEDLINE |
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