The role of mitochondrial apoptotic pathway in islet amyloid-induced β-cell death

2021 ◽  
pp. 111424
Author(s):  
Helen Y. Wong ◽  
Queenie Hui ◽  
Zhenyue Hao ◽  
Garth L. Warnock ◽  
Minna Woo ◽  
...  
Keyword(s):  
Cell Death ◽  
Β Cell ◽  
Islet Amyloid ◽  
Apoptotic Pathway ◽  
Mitochondrial Apoptotic Pathway

scholarly journals Redundant role of the cytochrome c-mediated intrinsic apoptotic pathway in pancreatic β-cells

2011 ◽  
Vol 210 (3) ◽  
pp. 285-292 ◽  
Author(s):  
Diana Choi ◽  
Stephanie A Schroer ◽  
Shun Yan Lu ◽  
Erica P Cai ◽  
Zhenyue Hao ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Apoptosis ◽  
Caspase 8 ◽  
Intrinsic Apoptotic Pathway ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Apoptotic Pathway ◽  
Redundant Role

Cytochrome c is one of the central mediators of the mitochondrial or the intrinsic apoptotic pathway. Mice harboring a ‘knock-in’ mutation of cytochrome c, impairing only its apoptotic function, have permitted studies on the essential role of cytochrome c-mediated apoptosis in various tissue homeostasis. To this end, we examined the role of cytochrome c in pancreatic β-cells under homeostatic conditions and in diabetes models, including those induced by streptozotocin (STZ) and c-Myc. Previous studies have shown that both STZ- and c-Myc-induced β-cell apoptosis is mediated through caspase-3 activation; however, the precise mechanism in these modes of cell death was not characterized. The results of our study show that lack of functional cytochrome c does not affect glucose homeostasis or pancreatic β-cell mass under basal conditions. Moreover, the cytochrome c-mediated intrinsic apoptotic pathway is required for neither STZ- nor c-Myc-induced β-cell death. We also observed that the extrinsic apoptotic pathway mediated through caspase-8 was not essential in c-Myc-induced β-cell destruction. These findings suggest that cytochrome c is not required for STZ-induced β-cell apoptosis and, together with the caspase-8-mediated extrinsic pathway, plays a redundant role in c-Myc-induced β-cell apoptosis.

scholarly journals An autophagy enhancer ameliorates diabetes of human IAPP-transgenic mice through clearance of amyloidogenic oligomer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jinyoung Kim ◽  
Kihyoun Park ◽  
Min Jung Kim ◽  
Hyejin Lim ◽  
Kook Hwan Kim ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Therapeutic Modality ◽  
Protective Effects ◽  
Β Cells ◽  
Β Cell ◽  
Islet Amyloid ◽  
Amyloid Accumulation ◽  
Human Diabetes

AbstractWe have reported that autophagy is crucial for clearance of amyloidogenic human IAPP (hIAPP) oligomer, suggesting that an autophagy enhancer could be a therapeutic modality against human diabetes with amyloid accumulation. Here, we show that a recently identified autophagy enhancer (MSL-7) reduces hIAPP oligomer accumulation in human induced pluripotent stem cell-derived β-cells (hiPSC-β-cells) and diminishes oligomer-mediated apoptosis of β-cells. Protective effects of MSL-7 against hIAPP oligomer accumulation and hIAPP oligomer-mediated β-cell death are significantly reduced in cells with knockout of MiTF/TFE family members such as Tfeb or Tfe3. MSL-7 improves glucose tolerance and β-cell function of hIAPP+ mice on high-fat diet, accompanied by reduced hIAPP oligomer/amyloid accumulation and β-cell apoptosis. Protective effects of MSL-7 against hIAPP oligomer-mediated β-cell death and the development of diabetes are also significantly reduced by β-cell-specific knockout of Tfeb. These results suggest that an autophagy enhancer could have therapeutic potential against human diabetes characterized by islet amyloid accumulation.

scholarly journals Deficiency of VCP-Interacting Membrane Selenoprotein (VIMP) Leads to G1 Cell Cycle Arrest and Cell Death in MIN6 Insulinoma Cells

2018 ◽  
Vol 51 (5) ◽  
pp. 2185-2197 ◽  
Author(s):  
Lili Men ◽  
Juan Sun ◽  
Decheng Ren
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Insulin Secretion ◽  
Cell Apoptosis ◽  
Β Cells ◽  
Β Cell ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest ◽  
Insulinoma Cells

Background/Aims: VCP-interacting membrane selenoprotein (VIMP), an ER resident selenoprotein, is highly expressed in β-cells, however, the role of VIMP in β-cells has not been characterized. In this study, we studied the relationship between VIMP deficiency and β-cell survival in MIN6 insulinoma cells. Methods: To determine the role of VIMP in β-cells, lentiviral VIMP shRNAs were used to knock down (KD) expression of VIMP in MIN6 cells. Cell death was quantified by propidium iodide (PI) staining followed by flow cytometric analyses using a FACS Caliber and FlowJo software. Cell apoptosis and proliferation were determined by TUNEL assay and Ki67 staining, respectively. Cell cycle was analyzed after PI staining. Results: The results show that 1) VIMP suppression induces β-cell apoptosis, which is associated with a decrease in Bcl-xL, and the β-cell apoptosis induced by VIMP suppression can be inhibited by overexpression of Bcl-xL; 2) VIMP knockdown (KD) decreases cell proliferation and G1 cell cycle arrest by accumulating p27 and decreasing E2F1; 3) VIMP KD suppresses unfolded protein response (UPR) activation by regulating the IRE1α and PERK pathways; 4) VIMP KD increases insulin secretion. Conclusion: These results suggest that VIMP may function as a novel regulator to modulate β-cell survival, proliferation, cell cycle, UPR and insulin secretion in MIN6 cells.

Helicobacter hepaticusCytolethal Distending Toxin Causes Cell Death in Intestinal Epithelial Cells via Mitochondrial Apoptotic Pathway

Helicobacter ◽  
2010 ◽  
Vol 15 (2) ◽  
pp. 98-107 ◽  
Author(s):  
Namal P. M. Liyanage ◽  
Karoline C. Manthey ◽  
Rohana P. Dassanayake ◽  
Charles A. Kuszynski ◽  
Gregory G. Oakley ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Apoptotic Pathway ◽  
Mitochondrial Apoptotic Pathway

The role of FAS/FASLig and apoptosis in β-cell death in animal models: relevance for human IDDM

1998 ◽  
Vol 14 (2) ◽  
pp. 194-195 ◽  
Author(s):  
Carla Giordano ◽  
Pierina Richiusa ◽  
Maria Stella Sbriglia ◽  
Giuseppe Pizzolanti
Keyword(s):  
Cell Death ◽  
Animal Models ◽  
Β Cell

scholarly journals Mitochondria-Ros Crosstalk in the Control of Cell Death and Aging

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Saverio Marchi ◽  
Carlotta Giorgi ◽  
Jan M. Suski ◽  
Chiara Agnoletto ◽  
Angela Bononi ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Redox State ◽  
Balance Of Power ◽  
Molecular Pathways ◽  
Oxygen Species ◽  
Intrinsic Apoptotic Pathway ◽  
Apoptotic Pathway ◽  
Induce Cell Death

Reactive oxygen species (ROS) are highly reactive molecules, mainly generated inside mitochondria that can oxidize DNA, proteins, and lipids. At physiological levels, ROS function as “redox messengers” in intracellular signalling and regulation, whereas excess ROS induce cell death by promoting the intrinsic apoptotic pathway. Recent work has pointed to a further role of ROS in activation of autophagy and their importance in the regulation of aging. This review will focus on mitochondria as producers and targets of ROS and will summarize different proteins that modulate the redox state of the cell. Moreover, the involvement of ROS and mitochondria in different molecular pathways controlling lifespan will be reported, pointing out the role of ROS as a “balance of power,” directing the cell towards life or death.

The role of FOXO1 in palmitate-induced β-cell death

2015 ◽  
Vol 10 (S 01) ◽  
Author(s):  
M Panse ◽  
F Gerst ◽  
G Kaiser ◽  
HU Häring ◽  
S Ullrich
Keyword(s):  
Cell Death ◽  
Β Cell

The role of lysosomes in BDE 47-mediated activation of mitochondrial apoptotic pathway in HepG2 cells

Chemosphere ◽  
2015 ◽  
Vol 124 ◽  
pp. 10-21 ◽  
Author(s):  
Xiaohui Liu ◽  
Jian Wang ◽  
Chengquan Lu ◽  
Chunyan Zhu ◽  
Bo Qian ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Apoptotic Pathway ◽  
Mitochondrial Apoptotic Pathway
Sign in / Sign up

Export Citation Format

Share Document