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Pyruvate Kinase 2, an Energy Metabolism Related Enzyme, May Have a Neuroprotective Function in Retinal Degeneration

Zhou, Jiaming LU and Ekström, Per LU (2023) In ASN Neuro 15.
Abstract

Retinitis pigmentosa (RP) is an inherited disorder that results in vision impairment but general and mutation-independent therapeutic strategies are not available. However, it is widely regarded that the cGMP system, including cGMP and its interactor cGMP-dependent protein kinase (PKG), acts as a crucial effector during retinal degeneration. We have previously identified a list of cGMP-PKG-dependent genes in the context of RP, and in this study, we further validated one of these, namely pyruvate kinase 2 (PKM2), and investigated the potential role of PKM2 for the photoreceptors’ well-being during RP. With the aid of organotypic retinal explant cultures, we pharmacologically manipulated the PKM2 activities in two different RP mouse... (More)

Retinitis pigmentosa (RP) is an inherited disorder that results in vision impairment but general and mutation-independent therapeutic strategies are not available. However, it is widely regarded that the cGMP system, including cGMP and its interactor cGMP-dependent protein kinase (PKG), acts as a crucial effector during retinal degeneration. We have previously identified a list of cGMP-PKG-dependent genes in the context of RP, and in this study, we further validated one of these, namely pyruvate kinase 2 (PKM2), and investigated the potential role of PKM2 for the photoreceptors’ well-being during RP. With the aid of organotypic retinal explant cultures, we pharmacologically manipulated the PKM2 activities in two different RP mouse models (rd2 and rd10) via the addition of TEPP-46 (a PKM2 activator) and found that activation of PKM2 alleviates the progress of photoreceptor death in the rd10 mouse model. We also noted that the expression of both PKM2 and one of its targets, glucose transporter-1 (Glut1), showed alterations depending on the degeneration state. The observations provide supportive evidence that PKM2 may serve as a novel potential molecular target in RP.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cell death, organotypic retinal explant culture, PKM2, retinal degeneration, TUNEL
in
ASN Neuro
volume
15
publisher
Portland Press
external identifiers
  • scopus:85148264493
  • pmid:36799552
ISSN
1759-0914
DOI
10.1177/17590914231151534
language
English
LU publication?
yes
id
c70496ac-9d0e-4856-a958-3c2acb5f9b6f
date added to LUP
2023-03-08 09:41:38
date last changed
2024-06-13 12:57:16
@article{c70496ac-9d0e-4856-a958-3c2acb5f9b6f,
  abstract     = {{<p>Retinitis pigmentosa (RP) is an inherited disorder that results in vision impairment but general and mutation-independent therapeutic strategies are not available. However, it is widely regarded that the cGMP system, including cGMP and its interactor cGMP-dependent protein kinase (PKG), acts as a crucial effector during retinal degeneration. We have previously identified a list of cGMP-PKG-dependent genes in the context of RP, and in this study, we further validated one of these, namely pyruvate kinase 2 (PKM2), and investigated the potential role of PKM2 for the photoreceptors’ well-being during RP. With the aid of organotypic retinal explant cultures, we pharmacologically manipulated the PKM2 activities in two different RP mouse models (rd2 and rd10) via the addition of TEPP-46 (a PKM2 activator) and found that activation of PKM2 alleviates the progress of photoreceptor death in the rd10 mouse model. We also noted that the expression of both PKM2 and one of its targets, glucose transporter-1 (Glut1), showed alterations depending on the degeneration state. The observations provide supportive evidence that PKM2 may serve as a novel potential molecular target in RP.</p>}},
  author       = {{Zhou, Jiaming and Ekström, Per}},
  issn         = {{1759-0914}},
  keywords     = {{cell death; organotypic retinal explant culture; PKM2; retinal degeneration; TUNEL}},
  language     = {{eng}},
  publisher    = {{Portland Press}},
  series       = {{ASN Neuro}},
  title        = {{Pyruvate Kinase 2, an Energy Metabolism Related Enzyme, May Have a Neuroprotective Function in Retinal Degeneration}},
  url          = {{http://dx.doi.org/10.1177/17590914231151534}},
  doi          = {{10.1177/17590914231151534}},
  volume       = {{15}},
  year         = {{2023}},
}