open access publication

Article, 2021

HSPB1 influences mitochondrial respiration in ER-stressed beta cells

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, ISSN 1878-2434, 1570-9639, 1878-1454, Volume 1869, 9, Page 140680, 10.1016/j.bbapap.2021.140680

Contributors

Mule, Simon Ngao 0000-0001-6073-6341 [1] Gomes, Vinícius De Morais [1] Wailemann, Rosangela A Mansano 0000-0003-4909-9657 [1] Macedo-Da-Silva, Janaina [1] Rosa-Fernandes, Livia 0000-0003-1612-1950 [1] Larsen, Martin Røssel 0000-0001-6203-0123 [2] Labriola, Leticia (Corresponding author) [1] Palmisano, Giuseppe 0000-0003-1336-6151 (Corresponding author) [1]

Affiliations

  1. [1] Universidade de São Paulo
    2. [NORA names: Brazil; America, South];
  2. [2] University of Southern Denmark
    3. [NORA names: SDU University of Southern Denmark; University; Denmark; Europe, EU; Nordic; OECD]

Abstract

Beta-cell death and dysfunction are involved in the development of type 1 and 2 diabetes. ER-stress impairs beta-cells function resulting in pro-apoptotic stimuli that promote cell death. Hence, the identification of protective mechanisms in response to ER-stress could lead to novel therapeutic targets and insight in the pathology of these diseases. Here, we report the identification of proteins involved in dysregulated pathways upon thapsigargin treatment of MIN6 cells. Utilizing quantitative proteomics we identified upregulation of proteins involved in protein folding, unfolded protein response, redox homeostasis, proteasome processes associated with endoplasmic reticulum and downregulation of TCA cycle, cellular respiration, lipid metabolism and ribosome assembly processes associated to mitochondria and eukaryotic initiation translation factor components. Subsequently, pro-inflammatory cytokine treatment was performed to mimic pathological changes observed in beta-cells during diabetes. Cytokines induced ER stress and impaired mitochondrial function in beta-cells corroborating the results obtained with the proteomic approach. HSPB1 levels are increased by prolactin on pancreatic beta-cells and this protein is a key factor for cytoprotection although its role has not been fully elucidated. Here we show that while up-regulation of HSPB1 was able to restore the mitochondrial dysfunction induced by beta-cells' exposure to inflammatory cytokines, silencing of this chaperone abrogated the beneficial effects promoted by PRL. Taken together, our results outline the importance of HSPB1 to mitigate beta-cell dysfunction. Further studies are needed to elucidate its role in diabetes.

Keywords

ER stress, HSPB1, HSPB1 levels, MIN6 cells, PRL, TCA cycle, approach, assembly process, beneficial effects, beta cells, beta-cell death, beta-cell dysfunction, beta-cell function, beta-cells, cell death, cells, cellular respiration, changes, chaperone, components, cycle, cytokine treatment, cytokines, cytoprotection, death, development, development of type 1, diabetes, disease, downregulation, downregulation of TCA cycle, dysfunction, dysregulated pathways, effect, endoplasmic reticulum, exposure to inflammatory cytokines, factor components, factors, folding, function, homeostasis, identification, identification of protective mechanisms, identification of proteins, impaired mitochondrial function, inflammatory cytokines, levels, lipid, lipid metabolism, mechanism, metabolism, mitochondria, mitochondrial dysfunction, mitochondrial function, mitochondrial respiration, pancreatic beta-cells, pathological changes, pathology, pathway, pro-apoptotic stimuli, pro-inflammatory cytokine treatment, process, prolactin, promote cell death, proteasome, protective mechanisms, protein, protein folding, protein response, proteomic approach, proteomics, quantitative proteomics, redox, redox homeostasis, respiration, response, response to ER stress, results, reticulum, ribosome, ribosome assembly process, silencing, stimuli, stress, study, target, thapsigargin, thapsigargin treatment, therapeutic target, treatment, treatment of MIN6 cells, type 1, unfolded protein response, up-regulated, upregulation, upregulation of proteins

Funders

  • São Paulo Research Foundation
  • Coordenação de Aperfeicoamento de Pessoal de Nível Superior
  • National Council for Scientific and Technological Development

Data Provider: Digital Science

LINKS
-

Matching Records in NORA

SUBJECTS
+

METRICS
+