PMID- 36100124
OWN - NLM
STAT- MEDLINE
DCOM- 20221011
LR  - 20221013
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Linking)
VI  - 557
DP  - 2022 Nov 1
TI  - Proteomic examination of Cornus officinalis stimulated 1.1B4 human pancreatic 
      cells reveals activation of autophagy and Keap1/Nrf2 pathway.
PG  - 111773
LID - S0303-7207(22)00221-0 [pii]
LID - 10.1016/j.mce.2022.111773 [doi]
AB  - Type 1 diabetes (T1D) is an autoimmune disease initiated by genetic 
      predisposition and environmental influences culminating in the immunologically 
      mediated destruction of pancreatic beta-cells with eventual loss of insulin 
      production. Although T1D can be accurately predicted via autoantibodies, 
      therapies are lacking that can intercede autoimmunity and protect pancreatic 
      beta-cells. There are no approved interventional modalities established for this 
      purpose. One such potential source for clinical agents of this use is from the 
      frequently utilized Cornus officinalis (CO) in the field of ethnopharmacology. 
      Studies by our lab and others have demonstrated that CO has robust proliferative, 
      metabolic, and cytokine protective effects on pancreatic beta-cells. To identify the 
      molecular mechanism of the biological effects of CO, we performed a proteomic and 
      phosphoproteomic analysis examining the cellular networks impacted by CO 
      application on the 1.1B4 pancreatic beta-cell line. Our label-free mass spectrometry 
      approach has demonstrated significant increased phosphorylation of the selective 
      autophagy receptor of p62 (Sequestosome-1/SQSTM1/p62) and predicted activation of 
      the antioxidant Kelch-like ECH-associated protein 1 (Keap1)/Nuclear 
      factor-erythroid factor 2-related factor 2 (Nrf2) pathway. Further validation by 
      immunoblotting and immunofluorescence revealed markers of autophagy such as 
      increased LC3-II and decreased total p62 along with nuclear localization of Nrf2. 
      Both autophagy and the Keap1/Nrf2 pathways have been shown to be impaired in 
      human and animal models of T1D and may serve as an excellent potential 
      therapeutic target stimulated by CO.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Sharp-Tawfik, Arielle
AU  - Sharp-Tawfik A
AD  - Department of Cell Biology, Microbiology and Molecular Biology, University of 
      South Florida, Tampa, FL, 33620, USA.
FAU - Fletcher, Justin D
AU  - Fletcher JD
AD  - Department of Cell Biology, Microbiology and Molecular Biology, University of 
      South Florida, Tampa, FL, 33620, USA.
FAU - Guergues, Jennifer
AU  - Guergues J
AD  - Department of Cell Biology, Microbiology and Molecular Biology, University of 
      South Florida, Tampa, FL, 33620, USA.
FAU - Marelia-Bennett, Catherine
AU  - Marelia-Bennett C
AD  - Department of Pathology & Laboratory Medicine at the Medical University of South 
      Carolina in Charleston, SC, 29425, USA.
FAU - Wolf, Tiara J
AU  - Wolf TJ
AD  - Department of Cell Biology, Microbiology and Molecular Biology, University of 
      South Florida, Tampa, FL, 33620, USA.
FAU - Coiner, Alexis M
AU  - Coiner AM
AD  - Department of Cell Biology, Microbiology and Molecular Biology, University of 
      South Florida, Tampa, FL, 33620, USA.
FAU - Zhang, Y Clare
AU  - Zhang YC
AD  - Practice of Oriental Medicine, Tucson, AZ, 85716, USA.
FAU - Stevens, Stanley M Jr
AU  - Stevens SM Jr
AD  - Department of Cell Biology, Microbiology and Molecular Biology, University of 
      South Florida, Tampa, FL, 33620, USA.
FAU - Burkhardt, Brant R
AU  - Burkhardt BR
AD  - Department of Cell Biology, Microbiology and Molecular Biology, University of 
      South Florida, Tampa, FL, 33620, USA. Electronic address: bburkhardt@usf.edu.
LA  - eng
PT  - Journal Article
DEP - 20220911
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Antioxidants)
RN  - 0 (Autoantibodies)
RN  - 0 (Cytokines)
RN  - 0 (Insulins)
RN  - 0 (KEAP1 protein, human)
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Sequestosome-1 Protein)
SB  - IM
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Autoantibodies
MH  - Autophagy/physiology
MH  - *Cornus
MH  - Cytokines/metabolism
MH  - *Diabetes Mellitus, Type 1
MH  - Humans
MH  - *Insulins/metabolism
MH  - Kelch-Like ECH-Associated Protein 1/metabolism
MH  - NF-E2-Related Factor 2/metabolism
MH  - Oxidative Stress
MH  - Proteomics
MH  - Sequestosome-1 Protein/metabolism
OTO - NOTNLM
OT  - Autophagy
OT  - Cornus officinalis
OT  - Keap1/Nrf2
OT  - Proteomics
OT  - Type 1 diabetes
OT  - p62
COIS- Declaration of competing interest Authors do not have any conflict of interest.
EDAT- 2022/09/14 06:00
MHDA- 2022/10/12 06:00
CRDT- 2022/09/13 19:24
PHST- 2022/05/12 00:00 [received]
PHST- 2022/08/19 00:00 [revised]
PHST- 2022/09/01 00:00 [accepted]
PHST- 2022/09/14 06:00 [pubmed]
PHST- 2022/10/12 06:00 [medline]
PHST- 2022/09/13 19:24 [entrez]
AID - S0303-7207(22)00221-0 [pii]
AID - 10.1016/j.mce.2022.111773 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2022 Nov 1;557:111773. doi: 10.1016/j.mce.2022.111773. Epub 
      2022 Sep 11.