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ßA1-crystallin regulates glucose metabolism and mitochondrial function in mouse retinal astrocytes by modulating PTP1B activity.
Ghosh, Sayan; Liu, Haitao; Yazdankhah, Meysam; Stepicheva, Nadezda; Shang, Peng; Vaidya, Tanuja; Hose, Stacey; Gupta, Urvi; Calderon, Michael Joseph; Hu, Ming-Wen; Nair, Archana Padmanabhan; Weiss, Joseph; Fitting, Christopher S; Bhutto, Imran A; Gadde, Santosh Gopi Krishna; Naik, Naveen Kumar; Jaydev, Chaitra; Lutty, Gerard A; Handa, James T; Jayagopal, Ashwath; Qian, Jiang; Sahel, José-Alain; Rajasundaram, Dhivyaa; Sergeev, Yuri; Zigler, J Samuel; Sethu, Swaminathan; Watkins, Simon; Ghosh, Arkasubhra; Sinha, Debasish.
Afiliação
  • Ghosh S; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Liu H; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Yazdankhah M; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Stepicheva N; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Shang P; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Vaidya T; GROW Research Laboratory, Narayana Nethralaya Foundation, Bengaluru, India.
  • Hose S; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Gupta U; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Calderon MJ; Department of Cell Biology and Center for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Hu MW; Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Nair AP; GROW Research Laboratory, Narayana Nethralaya Foundation, Bengaluru, India.
  • Weiss J; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Fitting CS; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Bhutto IA; Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Gadde SGK; GROW Research Laboratory, Narayana Nethralaya Foundation, Bengaluru, India.
  • Naik NK; GROW Research Laboratory, Narayana Nethralaya Foundation, Bengaluru, India.
  • Jaydev C; GROW Research Laboratory, Narayana Nethralaya Foundation, Bengaluru, India.
  • Lutty GA; Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Handa JT; Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Jayagopal A; Kodiak Sciences, Palo Alto, CA, USA.
  • Qian J; Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Sahel JA; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Rajasundaram D; Institut de la Vision, INSERM, CNRS, Sorbonne Université, Paris, France.
  • Sergeev Y; Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Zigler JS; National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
  • Sethu S; Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Watkins S; GROW Research Laboratory, Narayana Nethralaya Foundation, Bengaluru, India.
  • Ghosh A; Department of Cell Biology and Center for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Sinha D; GROW Research Laboratory, Narayana Nethralaya Foundation, Bengaluru, India.
Commun Biol ; 4(1): 248, 2021 02 24.
Article em En | MEDLINE | ID: mdl-33627831
ABSTRACT
ßA3/A1-crystallin, a lens protein that is also expressed in astrocytes, is produced as ßA3 and ßA1-crystallin isoforms by leaky ribosomal scanning. In a previous human proteome high-throughput array, we found that ßA3/A1-crystallin interacts with protein tyrosine phosphatase 1B (PTP1B), a key regulator of glucose metabolism. This prompted us to explore possible roles of ßA3/A1-crystallin in metabolism of retinal astrocytes. We found that ßA1-crystallin acts as an uncompetitive inhibitor of PTP1B, but ßA3-crystallin does not. Loss of ßA1-crystallin in astrocytes triggers metabolic abnormalities and inflammation. In CRISPR/cas9 gene-edited ßA1-knockdown (KD) mice, but not in ßA3-knockout (KO) mice, the streptozotocin (STZ)-induced diabetic retinopathy (DR)-like phenotype is exacerbated. Here, we have identified ßA1-crystallin as a regulator of PTP1B; loss of this regulation may be a new mechanism by which astrocytes contribute to DR. Interestingly, proliferative diabetic retinopathy (PDR) patients showed reduced ßA1-crystallin and higher levels of PTP1B in the vitreous humor.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Retina / Astrócitos / Cadeia A de beta-Cristalina / Retinopatia Diabética / Metabolismo Energético / Proteína Tirosina Fosfatase não Receptora Tipo 1 / Glucose / Mitocôndrias Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Retina / Astrócitos / Cadeia A de beta-Cristalina / Retinopatia Diabética / Metabolismo Energético / Proteína Tirosina Fosfatase não Receptora Tipo 1 / Glucose / Mitocôndrias Idioma: En Ano de publicação: 2021 Tipo de documento: Article