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The Effects of Potato's Processed Toxicant and Natural Toxin in the Presence of Antioxidants on AKT/PKB Signaling Pathway and Its Downstream Regulatory Genes in BEAS-2B Cells.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	The Effects of Potato's Processed Toxicant and Natural Toxin in the Presence of Antioxidants on AKT/PKB Signaling Pathway and Its Downstream Regulatory Genes in BEAS-2B Cells./
作者:	Eltayeb, Hoda Awad.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
面頁冊數:	150 p.
附註:	Source: Dissertations Abstracts International, Volume: 82-01, Section: B.
Contained By:	Dissertations Abstracts International82-01B.
標題:	Environmental science. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=27962845
ISBN:	9798662401228

The Effects of Potato's Processed Toxicant and Natural Toxin in the Presence of Antioxidants on AKT/PKB Signaling Pathway and Its Downstream Regulatory Genes in BEAS-2B Cells.
Eltayeb, Hoda Awad.

The Effects of Potato's Processed Toxicant and Natural Toxin in the Presence of Antioxidants on AKT/PKB Signaling Pathway and Its Downstream Regulatory Genes in BEAS-2B Cells. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 150 p.

Source: Dissertations Abstracts International, Volume: 82-01, Section: B.

Thesis (Ph.D.)--Texas Southern University, 2020.

This item must not be sold to any third party vendors.

Almost all living things are directly or indirectly exposed to different types of chemicals in their environment. When living cells are exposed to toxic chemical(s), they usually trigger cellular responses that ultimately alter the cells behavior, which the cells either endure or are detrimental to the cells. Cells exposed to toxic chemicals induce free radicals that cause oxidative stress. Normally, cells produce free radicals and antioxidants during cellular metabolism, yet free radicals cause damages to cellular materials, such as nucleic acids (DNA and RNA), proteins and lipids. Free radicals can also be removed from cells by antioxidants that are also found in consumable foods. Antioxidants inhibit oxidation, which produces free radicals; and free radicals have been implicated in several human diseases. Therefore, the specific aim of this study is to demonstrate the synergistic toxic effects of two compounds found in potato products, acrylamide (i.e. a toxicant generated when potato is cooked at higher temperature) and alpha (α)-solanine (i.e. a natural occurring toxin) in the presence of antioxidants, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) which prevent formation of free radicals. Acrylamide affects nervous systems, alters male animal’s reproduction, and causes cancer in animals. On the other hand, α-solanine causes gastrointestinal and neurological disorders.The goal of this study is to demonstrate that the potato's processed toxicant and natural toxin (xenobiotics) will synergistically alter cellular response, which will derail cell behavior and several signaling pathways. The rationale of this study is that there is no study on the synergistic toxic effects of two toxic compounds found in potato products, which are acrylamide and α-solanine. To understand synergistic toxic effects acrylamide and α-solanine in cells, three aims and hypotheses were developed.Aim 1: to demonstrate that in the presence or absence of antioxidants, the morphology of BEAS-2B cells will change when exposed synergistically to potato's processed toxicant (acrylamide) and natural toxin (α-solanine). The working hypothesis for aim 1 is as follow—treatment of BEAS-2B cells with antioxidants (BHA and BHT) for 24 h, which is followed by concurrent treatment of the cells with acrylamide and α-solanine for 48 h is not or unlikely sufficient to prevent profound morphological damages to the cells when compared to their individual treatment.Aim 2: to demonstrate that the morphological changes afflicted in the BEAS-2B cells by the synergistic effects of acrylamide and α-solanine will change genomic materials activities, which will also change cellular functions and lead to cell death. The working hypothesis for aim 2 is as follow—any changes in the cell’s morphology will likely inhibit the functions of the genetic materials and the cellular responses in the BEAS-2B cells, which eventually will cause the cells to undergo untimely cell death or crenation.Aim 3: to demonstrate that the changes caused in the genomic materials (i.e. including the cellular functions) by the synergistic effects of acrylamide and α-solanine will disrupt either the survival or the apoptosis pathways that are controlled by AKT/PKB and its downstream regulators. The working hypothesis for aim 3 is as follow—any changes in the genomic material’s activities in the BEAS-2B cells will inhibit cellular functions, which will derail the AKT/PKB signaling pathway and other downstream AKT/PKB controlled pathways afterward causing the cells to become helpless and undergo untimely cell death.Findings from this study showed that the presence of antioxidants (BHA and BHT) is not sufficient to prevent the synergistic toxic effects of acrylamide (3.5 mM) and α-solanine (0.044 M) in BEAS-2B cells. Synergistically acrylamide and α-solanine altered the morphology of BEAS-2B cells when compared to half concentration of acrylamide (3.5 mM) and α-solanine (0.044 M), which caused moderate change in the morphology of BEAS-2B cells. Individually acrylamide at (3.5 mM) and α-solanine (0.044 M) concentration caused highly moderate and/or minimum changes in the morphology of BEAS-2B cells, which suggests the individual toxic effects of each chemical is less deleterious than the synergistic effects of acrylamide and α-solanine at their individual (3.5 mM) and (0.044 M) concentration. Polymerase chain reaction (PCR) was used to determine DNA activities—synergistically acrylamide (3.5 mM) and α-solanine (0.044 M) showed reduced RNA than the individual chemical alone and/or synergistic acrylamide (3.5 mM) and α-solanine (0.044 M) at their individual reduced dose. The RNA was not broken, since the cDNA did amplify by PCR. The DNA phosphadiester bond breakage was not observed with the synergistic treatment of acrylamide (3.5 mM) and α-solanine (0.044 M) and/or acrylamide (3.5 mM) in BEAS-2B cells, suggesting the toxicant and the toxin do not have a direct effect on DNA or RNA. Furthermore, Western blot analysis was used to determine cellular responses—protein expression of AKT/PKB, as well as few-selected AKT/PKB downstream controlled genes, and DNA damage regulators were completely inhibited by the synergetic effects of acrylamide (3.5 mM) and α-solanine (0.044 M) and/or acrylamide (3.5 mM) in BEAS-2B cells. Synergetic effects of reduced dose of acrylamide (3.5 mM) and α-solanine (0.044 M) and/or α-solanine (0.044 M) alone showed minimal inhibitory effects on all the proteins analyzed in this study, which suggest that they have a less deleterious effect(s) in BEAS-2B cells. There were three control cells: a 24 h untreated control, which showed no changes in cell morphology and showed very low protein expression; and a 48 h untreated control and a 48 h mock control (i.e. treated with BHA and BHT for 24 h, which was followed by treatment of the cells with phosphate buffer saline (PBS) for 48 h functions.Conclusion from this study showed that antioxidants exert their protection only when the toxicity is at a reduced dose of acrylamide (3.5 mM) and α-solanine (0.044 M), which suggest that the cells are capable of recovering from the synergistic effect(s) of acrylamide (3.5 mM) and α-solanine (0.044 M). Alpha-solanine alone at (0.044 M) dose in the presence of antioxidants has less effect on the cells, but acrylamide alone at (3.5 mM) dose in the presence of antioxidants is also toxic to the cells. Finally, the overall findings of this study suggest that the reduced expression of selected genes in the AKT, NFKB and TP53 pathways is most likely due to crenation and necrosis, but not DNA damage.

ISBN: 9798662401228Subjects--Topical Terms:

1179128
Environmental science.
Subjects--Index Terms:

Acrylamide

The Effects of Potato's Processed Toxicant and Natural Toxin in the Presence of Antioxidants on AKT/PKB Signaling Pathway and Its Downstream Regulatory Genes in BEAS-2B Cells.
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506 $a This item must not be sold to any third party vendors.
520 $a Almost all living things are directly or indirectly exposed to different types of chemicals in their environment. When living cells are exposed to toxic chemical(s), they usually trigger cellular responses that ultimately alter the cells behavior, which the cells either endure or are detrimental to the cells. Cells exposed to toxic chemicals induce free radicals that cause oxidative stress. Normally, cells produce free radicals and antioxidants during cellular metabolism, yet free radicals cause damages to cellular materials, such as nucleic acids (DNA and RNA), proteins and lipids. Free radicals can also be removed from cells by antioxidants that are also found in consumable foods. Antioxidants inhibit oxidation, which produces free radicals; and free radicals have been implicated in several human diseases. Therefore, the specific aim of this study is to demonstrate the synergistic toxic effects of two compounds found in potato products, acrylamide (i.e. a toxicant generated when potato is cooked at higher temperature) and alpha (α)-solanine (i.e. a natural occurring toxin) in the presence of antioxidants, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) which prevent formation of free radicals. Acrylamide affects nervous systems, alters male animal’s reproduction, and causes cancer in animals. On the other hand, α-solanine causes gastrointestinal and neurological disorders.The goal of this study is to demonstrate that the potato's processed toxicant and natural toxin (xenobiotics) will synergistically alter cellular response, which will derail cell behavior and several signaling pathways. The rationale of this study is that there is no study on the synergistic toxic effects of two toxic compounds found in potato products, which are acrylamide and α-solanine. To understand synergistic toxic effects acrylamide and α-solanine in cells, three aims and hypotheses were developed.Aim 1: to demonstrate that in the presence or absence of antioxidants, the morphology of BEAS-2B cells will change when exposed synergistically to potato's processed toxicant (acrylamide) and natural toxin (α-solanine). The working hypothesis for aim 1 is as follow—treatment of BEAS-2B cells with antioxidants (BHA and BHT) for 24 h, which is followed by concurrent treatment of the cells with acrylamide and α-solanine for 48 h is not or unlikely sufficient to prevent profound morphological damages to the cells when compared to their individual treatment.Aim 2: to demonstrate that the morphological changes afflicted in the BEAS-2B cells by the synergistic effects of acrylamide and α-solanine will change genomic materials activities, which will also change cellular functions and lead to cell death. The working hypothesis for aim 2 is as follow—any changes in the cell’s morphology will likely inhibit the functions of the genetic materials and the cellular responses in the BEAS-2B cells, which eventually will cause the cells to undergo untimely cell death or crenation.Aim 3: to demonstrate that the changes caused in the genomic materials (i.e. including the cellular functions) by the synergistic effects of acrylamide and α-solanine will disrupt either the survival or the apoptosis pathways that are controlled by AKT/PKB and its downstream regulators. The working hypothesis for aim 3 is as follow—any changes in the genomic material’s activities in the BEAS-2B cells will inhibit cellular functions, which will derail the AKT/PKB signaling pathway and other downstream AKT/PKB controlled pathways afterward causing the cells to become helpless and undergo untimely cell death.Findings from this study showed that the presence of antioxidants (BHA and BHT) is not sufficient to prevent the synergistic toxic effects of acrylamide (3.5 mM) and α-solanine (0.044 M) in BEAS-2B cells. Synergistically acrylamide and α-solanine altered the morphology of BEAS-2B cells when compared to half concentration of acrylamide (3.5 mM) and α-solanine (0.044 M), which caused moderate change in the morphology of BEAS-2B cells. Individually acrylamide at (3.5 mM) and α-solanine (0.044 M) concentration caused highly moderate and/or minimum changes in the morphology of BEAS-2B cells, which suggests the individual toxic effects of each chemical is less deleterious than the synergistic effects of acrylamide and α-solanine at their individual (3.5 mM) and (0.044 M) concentration. Polymerase chain reaction (PCR) was used to determine DNA activities—synergistically acrylamide (3.5 mM) and α-solanine (0.044 M) showed reduced RNA than the individual chemical alone and/or synergistic acrylamide (3.5 mM) and α-solanine (0.044 M) at their individual reduced dose. The RNA was not broken, since the cDNA did amplify by PCR. The DNA phosphadiester bond breakage was not observed with the synergistic treatment of acrylamide (3.5 mM) and α-solanine (0.044 M) and/or acrylamide (3.5 mM) in BEAS-2B cells, suggesting the toxicant and the toxin do not have a direct effect on DNA or RNA. Furthermore, Western blot analysis was used to determine cellular responses—protein expression of AKT/PKB, as well as few-selected AKT/PKB downstream controlled genes, and DNA damage regulators were completely inhibited by the synergetic effects of acrylamide (3.5 mM) and α-solanine (0.044 M) and/or acrylamide (3.5 mM) in BEAS-2B cells. Synergetic effects of reduced dose of acrylamide (3.5 mM) and α-solanine (0.044 M) and/or α-solanine (0.044 M) alone showed minimal inhibitory effects on all the proteins analyzed in this study, which suggest that they have a less deleterious effect(s) in BEAS-2B cells. There were three control cells: a 24 h untreated control, which showed no changes in cell morphology and showed very low protein expression; and a 48 h untreated control and a 48 h mock control (i.e. treated with BHA and BHT for 24 h, which was followed by treatment of the cells with phosphate buffer saline (PBS) for 48 h functions.Conclusion from this study showed that antioxidants exert their protection only when the toxicity is at a reduced dose of acrylamide (3.5 mM) and α-solanine (0.044 M), which suggest that the cells are capable of recovering from the synergistic effect(s) of acrylamide (3.5 mM) and α-solanine (0.044 M). Alpha-solanine alone at (0.044 M) dose in the presence of antioxidants has less effect on the cells, but acrylamide alone at (3.5 mM) dose in the presence of antioxidants is also toxic to the cells. Finally, the overall findings of this study suggest that the reduced expression of selected genes in the AKT, NFKB and TP53 pathways is most likely due to crenation and necrosis, but not DNA damage.
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