Theses and Dissertations

ORCID

https://orcid.org/0000-0002-2495-3944

Issuing Body

Mississippi State University

Advisor

Cheng, Wen-Hsing

Committee Member

Komakech, Joel

Committee Member

Wu, Tung-Lung

Committee Member

Mathews, Rahel

Committee Member

Zhang, Li

Date of Degree

12-13-2024

Original embargo terms

Visible MSU only 2 years

Document Type

Dissertation - Campus Access Only

Major

Food Science, Nutrition and Health Promotion (Functional Foods, Nutrition and Health)

Degree Name

Doctor of Philosophy (Ph.D.)

College

College of Agriculture and Life Sciences

Department

Department of Biochemistry, Nutrition and Health Promotion

Abstract

Earlier studies have shown that low-hierarchy selenoproteins such as Selenoprotein H (SELENOH) are sensitive to selenium deficiency and are suggested to confer the protection of body selenium against age-related diseases like type-2 diabetes. Further investigations into the response of tissues and selenotranscriptomes to dietary selenium deficiency, age, and sex reveal distinct tissue-specific sexual dimorphic patterns of selenium status and selenotranscriptomes. The objective of this dissertation was to understand the physiological roles of SELENOH during mouse aging. Serum, liver, muscle, brain, lungs, and kidney were collected and stored at - 80ºC for immunoblotting. The protein expression of SELENOP, GPX1, GPX3, and TXNRD1 were assessed in target tissues. AKT T-308 phosphorylation was also assessed in peripheral tissues. Perkin Elmer ELAN DRC II ICP-MS was used to determine trace mineral distribution using appropriate isotopes for each element (82Se, 57Fe, 66Zn, 63Cu, 52Cr, 60Ni, and 59Co). Our results revealed that (1) SELENOH knockout mediates the effect of dietary selenium deficiency by decreasing AKT T-308 phosphorylation in the muscle and liver of 9 months mice by 47-80% and worsened by old age to various degrees; (2) Male and female GPX1 and SELENOP protein expressions were increased by SELENOH knockout and age in the different tissues except liver, indicating the downregulation of liver GPX1 during selenium deficiency to sustain SELENOP production and transport selenium to the kidney, brain and lung to maintain GPX1 and TXNRD1 expressions; and (3) SELENOH knockout altered the ionome of trace elements, zinc, iron, copper, nickel, chromium, selenium and cobalt in the tissues of male and female mice during aging with the kidney largely affected, followed by the muscle and lung while the liver was least affected. The findings suggest that SELENOH mediates the physiological role of dietary selenium deficiency during aging. SELENOH alters the distribution of trace elements, regulates the protein expression of SELENOP, GPX1 and TXNRD1 in different organs and decreased AKT T- 308 phosphorylation, which suggests that SELENOH plays a crucial protective role against T2D- like symptoms.

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