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The Role of Oxidative Stress in Remodeling the Cardiac Microtubule Cytoskeleton- [electronic resource]
The Role of Oxidative Stress in Remodeling the Cardiac Microtubule Cytoskeleton- [electronic resource]
상세정보
- 자료유형
- 학위논문파일 국외
- 최종처리일시
- 20240214095841
- ISBN
- 9798379942663
- DDC
- 574.191
- 서명/저자
- The Role of Oxidative Stress in Remodeling the Cardiac Microtubule Cytoskeleton - [electronic resource]
- 발행사항
- [S.l.]: : University of Minnesota., 2021
- 발행사항
- Ann Arbor : : ProQuest Dissertations & Theses,, 2021
- 형태사항
- 1 online resource(147 p.)
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-01, Section: B.
- 주기사항
- Advisor: Gardner, Melissa.
- 학위논문주기
- Thesis (Ph.D.)--University of Minnesota, 2021.
- 사용제한주기
- This item must not be sold to any third party vendors.
- 초록/해제
- 요약Microtubules are cylindrical cytoskeletal polymers composed of α/β-tubulin heterodimers that make up an ordered tubulin lattice. In cells, microtubules form a network that is a key component of the cellular cytoskeleton. Under pathological conditions of oxidative stress, we and others have found that cardiomyocytes, the contractile cells in the heart, display a denser microtubule cytoskeleton, which may lead to the progressive structural and functional cellular changes associated with myocardial ischemia and systolic dysfunction. This reorganization of the microtubule network occurs despite only small increases in tubulin expression, suggesting that alterations to microtubule length regulation and stability are involved. Using biophysical reconstitution experiments and live-cell imaging, we found that oxidative stress may synergistically increase the density of microtubules inside of cells by simultaneously increasing the length of dynamic, short-lived microtubules, while fostering the longevity of stable, long-lived microtubules. We found that microtubules subjected to oxidative stress undergo cysteine oxidation, and our electron and fluorescence microscopy experiments revealed that the locations of oxidized tubulin subunits within the microtubule had structural damage within the cylindrical tubulin lattice, consisting of holes and lattice openings. For dynamic microtubules, incorporation of stabilizing GTP-tubulin into these damaged lattice regions led to an increased frequency of rescue events (the transition from shortening to growth), and thus longer microtubules. For long-lived microtubules, these same structural defects facilitate entry of the enzyme αTAT1 into the microtubule lumen, where it catalyzes the acetylation of α-tubulin. This intraluminal acetylation has been shown to increase the lifetime of stable microtubules by conferring mechanical stability to the microtubule lattice. In this way, oxidative stress triggers a dramatic, pathogenic shift from a sparse microtubule network into a dense, longitudinally aligned microtubule network inside of cardiac myocytes, likely contributing to increased cellular stiffness and contractile dysfunction. Our results provide insight into myocardial changes in ischemic heart disease by describing a mechanism for the dramatic remodeling of the microtubule cytoskeletal network within cardiac myocytes subjected to oxidative stress.
- 일반주제명
- Biophysics.
- 일반주제명
- Biochemistry.
- 일반주제명
- Cellular biology.
- 키워드
- Acetylation
- 키워드
- Cardiac myocytes
- 키워드
- Microtubules
- 키워드
- Oxidative stress
- 키워드
- Tubulin
- 기타저자
- University of Minnesota Biochemistry Molecular Bio and Biophysics
- 기본자료저록
- Dissertations Abstracts International. 85-01B.
- 기본자료저록
- Dissertation Abstract International
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520240214095841
■006m o d
■007cr#unu||||||||
■020 ▼a9798379942663
■035 ▼a(MiAaPQ)AAI28540193
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574.191
■1001 ▼aGoldblum, Rebecca R.
■24510▼aThe Role of Oxidative Stress in Remodeling the Cardiac Microtubule Cytoskeleton▼h[electronic resource]
■260 ▼a[S.l.]:▼bUniversity of Minnesota. ▼c2021
■260 1▼aAnn Arbor :▼bProQuest Dissertations & Theses, ▼c2021
■300 ▼a1 online resource(147 p.)
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-01, Section: B.
■500 ▼aAdvisor: Gardner, Melissa.
■5021 ▼aThesis (Ph.D.)--University of Minnesota, 2021.
■506 ▼aThis item must not be sold to any third party vendors.
■520 ▼aMicrotubules are cylindrical cytoskeletal polymers composed of α/β-tubulin heterodimers that make up an ordered tubulin lattice. In cells, microtubules form a network that is a key component of the cellular cytoskeleton. Under pathological conditions of oxidative stress, we and others have found that cardiomyocytes, the contractile cells in the heart, display a denser microtubule cytoskeleton, which may lead to the progressive structural and functional cellular changes associated with myocardial ischemia and systolic dysfunction. This reorganization of the microtubule network occurs despite only small increases in tubulin expression, suggesting that alterations to microtubule length regulation and stability are involved. Using biophysical reconstitution experiments and live-cell imaging, we found that oxidative stress may synergistically increase the density of microtubules inside of cells by simultaneously increasing the length of dynamic, short-lived microtubules, while fostering the longevity of stable, long-lived microtubules. We found that microtubules subjected to oxidative stress undergo cysteine oxidation, and our electron and fluorescence microscopy experiments revealed that the locations of oxidized tubulin subunits within the microtubule had structural damage within the cylindrical tubulin lattice, consisting of holes and lattice openings. For dynamic microtubules, incorporation of stabilizing GTP-tubulin into these damaged lattice regions led to an increased frequency of rescue events (the transition from shortening to growth), and thus longer microtubules. For long-lived microtubules, these same structural defects facilitate entry of the enzyme αTAT1 into the microtubule lumen, where it catalyzes the acetylation of α-tubulin. This intraluminal acetylation has been shown to increase the lifetime of stable microtubules by conferring mechanical stability to the microtubule lattice. In this way, oxidative stress triggers a dramatic, pathogenic shift from a sparse microtubule network into a dense, longitudinally aligned microtubule network inside of cardiac myocytes, likely contributing to increased cellular stiffness and contractile dysfunction. Our results provide insight into myocardial changes in ischemic heart disease by describing a mechanism for the dramatic remodeling of the microtubule cytoskeletal network within cardiac myocytes subjected to oxidative stress.
■590 ▼aSchool code: 0130.
■650 4▼aBiophysics.
■650 4▼aBiochemistry.
■650 4▼aCellular biology.
■653 ▼aAcetylation
■653 ▼aCardiac myocytes
■653 ▼aMicrotubules
■653 ▼aOxidative stress
■653 ▼aTubulin
■653 ▼aMicrotubule cytoskeleton
■690 ▼a0786
■690 ▼a0487
■690 ▼a0379
■71020▼aUniversity of Minnesota▼bBiochemistry, Molecular Bio, and Biophysics.
■7730 ▼tDissertations Abstracts International▼g85-01B.
■773 ▼tDissertation Abstract International
■790 ▼a0130
■791 ▼aPh.D.
■792 ▼a2021
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T16930948▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
■980 ▼a202402▼f2024
