Abstract
Language | English |
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Pages | 1320-1329 |
Journal | Pancreas |
Volume | 45 |
Issue number | 9 |
DOIs | |
Publication status | Published - 1 Oct 2013 |
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Keywords
- 1.1B4 cells
- apoptosis
- beta cells
- chemicals
- oxidative stress
- toxicity
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Molecular mechanisms of toxicity and cell damage by chemicals in a human pancreatic beta cell line, 1.1B4. / Vasu, Srividya; McClenaghan, Neville; Flatt, Peter.
In: Pancreas, Vol. 45, No. 9, 01.10.2013, p. 1320-1329.Research output: Contribution to journal › Article
TY - JOUR
T1 - Molecular mechanisms of toxicity and cell damage by chemicals in a human pancreatic beta cell line, 1.1B4
AU - Vasu, Srividya
AU - McClenaghan, Neville
AU - Flatt, Peter
PY - 2013/10/1
Y1 - 2013/10/1
N2 - Objectives: Mechanisms of toxicity and cell damage were investigated in novel clonal human pancreatic beta cell line, 1.1B4, after exposure to streptozotocin, alloxan, ninhydrin, and hydrogen peroxide. Methods: Viability, DNA damage, insulin secretion/content, [Ca2+]i, andglucokinase/hexokinase, mRNA expression were measured by MTTassay, comet assay, radioimmunoassay, fluorometric imaging plate reader, enzymecoupled photometry, and real-time polymerase chain reaction, respectively. Results: Chemicals significantly reduced 1.1B4 cell viability in a time/concentration–dependent manner. Chronic 18-hour exposure decreased cellularinsulin, glucokinase, and hexokinase activities. Chemicals decreased transcription of INS, GCK, PCSK1, PCSK2, and GJA1 (involved in secretory function). Insulin release and [Ca2+]i responses to nutrients and membrane-depolarizing agents were impaired. Streptozotocin and alloxanup-regulated transcription of genes, SOD1 and SOD2 (antioxidant enzymes). Ninhydrin and hydrogen peroxide up-regulated SOD2 transcription, whereas alloxan and hydrogen peroxide increased CAT transcription. Chemicals induced DNA damage, apoptosis, and increasedcaspase 3/7 activity. Streptozotocin and alloxan decreased transcription of BCL2 while increasing transcription of BAX. Chemicals did not affect transcription of HSPA4 and HSPA5 and nitrite production. Conclusions: 1.1B4 cells represent a useful model of human beta cells. Chemicals impaired 1.1B4 cell secretory function and activated antioxidant defense and apoptotic pathways without
AB - Objectives: Mechanisms of toxicity and cell damage were investigated in novel clonal human pancreatic beta cell line, 1.1B4, after exposure to streptozotocin, alloxan, ninhydrin, and hydrogen peroxide. Methods: Viability, DNA damage, insulin secretion/content, [Ca2+]i, andglucokinase/hexokinase, mRNA expression were measured by MTTassay, comet assay, radioimmunoassay, fluorometric imaging plate reader, enzymecoupled photometry, and real-time polymerase chain reaction, respectively. Results: Chemicals significantly reduced 1.1B4 cell viability in a time/concentration–dependent manner. Chronic 18-hour exposure decreased cellularinsulin, glucokinase, and hexokinase activities. Chemicals decreased transcription of INS, GCK, PCSK1, PCSK2, and GJA1 (involved in secretory function). Insulin release and [Ca2+]i responses to nutrients and membrane-depolarizing agents were impaired. Streptozotocin and alloxanup-regulated transcription of genes, SOD1 and SOD2 (antioxidant enzymes). Ninhydrin and hydrogen peroxide up-regulated SOD2 transcription, whereas alloxan and hydrogen peroxide increased CAT transcription. Chemicals induced DNA damage, apoptosis, and increasedcaspase 3/7 activity. Streptozotocin and alloxan decreased transcription of BCL2 while increasing transcription of BAX. Chemicals did not affect transcription of HSPA4 and HSPA5 and nitrite production. Conclusions: 1.1B4 cells represent a useful model of human beta cells. Chemicals impaired 1.1B4 cell secretory function and activated antioxidant defense and apoptotic pathways without
KW - 1.1B4 cells
KW - apoptosis
KW - beta cells
KW - chemicals
KW - oxidative stress
KW - toxicity
U2 - 10.1097/MPA.0000000000000645
DO - 10.1097/MPA.0000000000000645
M3 - Article
VL - 45
SP - 1320
EP - 1329
JO - Pancreas
T2 - Pancreas
JF - Pancreas
SN - 0885-3177
IS - 9
ER -