Skip to Main Content
 

Global Search Box

 
 
 

ETD Abstract Container

Abstract Header

TISSUE SPECIFIC PROTEIN SULFHYDRATION PROFILING UNDER DIETARY RESTRICTION, AGING, AND NEUROONCOLOGICAL DISEASE

Bithi, Nazmin
http://orcid.org/0000-0002-2843-034X
http://rave.ohiolink.edu/etdc/view?acc_num=csu1621512938809143

Abstract Details

2021, Doctor of Philosophy in Clinical-Bioanalytical Chemistry, Cleveland State University, College of Sciences and Health Professions.
Aging and aging associated disorders like cardiovascular disease, glioblastoma multiform (GBM), neurodegeneration, and diabetes currently and increasingly continue to be medical challenges as the 21st century progresses. Better insights into the molecular underpinnings of aging related declines will enable effective treatments that target not just the symptoms of these diseases but aging as a whole. Dietary restriction (DR) without malnutrition is one of the most effective interventions to delay the onset of aging and extend lifespan in model organisms. DR induces endogenous hydrogen sulfide (H2S) what is known as a cytoprotective redox-active metabolite serves as both an essential nutrient and selective pressure, resulting in cellular pathways for its production, utilization, and detoxification. Endogenously produced H2S stimulates metabolic, stress resistance, and longevity associated pathways. One potential mechanism of action for endogenous H2S is through posttranslational-sulfhydryl modifications of protein thiols, termed sulfhydration also known as persulfidation. Sulfhydration, similar to other posttranslational modifications, changes the activity, stability, and/or cellular localization of proteins. Despite the known importance of persulfidation, tissue-specific sulfhydrome profiles and their associated functions are not well characterized, specifically with respect to conditions and interventions known to modulate H2S production. We hypothesized that dietary restriction (DR), which increases lifespan and can boost H2S production, expands tissue-specific sulfhydromes. Here, we found protein persulfidation enriched in liver, kidney, muscle, and brain but decreased in heart of young and aged male mice under two forms of DR, with DR promoting persulfidation in numerous metabolic and aging-related pathways. Mice lacking cystathionine γ-lyase (CGL) had overall decreased tissue protein persulfidation numbers and failed to functionally augment sulfhydromes in response to DR, predominantly in kidney, muscle, and brain. Overall, we defined tissue- and CGL-dependent sulfhydromes and how diet transforms their makeup, underscoring the breadth for DR and H2S to impact biological processes and organismal health. We also observed that inhibition of H2S synthesis resulted in increased tumor cell proliferation and chemotherapy resistance while treatment with H2S donors led to cytotoxicity and death of cultured mouse and human Glioblastoma multiforme (GBM) cells. These findings suggest that H2S signaling serves to suppress GBM by restricting metabolic adaptability.
Christopher Hine, Dr. (Committee Co-Chair)
David Anderson, Dr. (Committee Co-Chair)
Analytical Chemistry; Chemistry

Recommended Citations

Citations

  • Bithi, N. (2021). TISSUE SPECIFIC PROTEIN SULFHYDRATION PROFILING UNDER DIETARY RESTRICTION, AGING, AND NEUROONCOLOGICAL DISEASE [Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1621512938809143

    APA Style (7th edition)

  • Bithi, Nazmin. TISSUE SPECIFIC PROTEIN SULFHYDRATION PROFILING UNDER DIETARY RESTRICTION, AGING, AND NEUROONCOLOGICAL DISEASE. 2021. Cleveland State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1621512938809143.

    MLA Style (8th edition)

  • Bithi, Nazmin. "TISSUE SPECIFIC PROTEIN SULFHYDRATION PROFILING UNDER DIETARY RESTRICTION, AGING, AND NEUROONCOLOGICAL DISEASE." Doctoral dissertation, Cleveland State University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=csu1621512938809143

    Chicago Manual of Style (17th edition)

csu1621512938809143
42
© , all rights reserved.
This open access ETD is published by Cleveland State University and OhioLINK.