The PKC/NOX/ROS and PYK2/MEK/ERK/PARP signalling pathways drive TRPM2 channel activation induced by non-cytolytic oxidative stress in microglial cells
Objectives: The study aimed to investigate the signalling mechanism for TRPM2 channel activation by non-cytolytic oxidative stress in microglia. Methods: Microglia from wild-type (WT) and TRPM2-knockout (KO) mice were exposed to 10-30 mM H2O2 for up to 24 hours. Morphological changes characteristic...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | en |
| Published: |
Taylor and Francis
2025
|
| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/123003/1/123003.pdf http://psasir.upm.edu.my/id/eprint/123003/ https://www.tandfonline.com/doi/full/10.1080/13510002.2025.2503131 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1858062462523277312 |
|---|---|
| author | Syed Mortadza, Sharifah Alawieyah Mohamad Zahir, Nur Zulaikha Wei, Chew Tze Jiang, Lin Hua |
| author_facet | Syed Mortadza, Sharifah Alawieyah Mohamad Zahir, Nur Zulaikha Wei, Chew Tze Jiang, Lin Hua |
| author_sort | Syed Mortadza, Sharifah Alawieyah |
| building | UPM Library |
| collection | Institutional Repository |
| content_provider | Universiti Putra Malaysia |
| content_source | UPM Institutional Repository |
| continent | Asia |
| country | Malaysia |
| description | Objectives: The study aimed to investigate the signalling mechanism for TRPM2 channel activation by non-cytolytic oxidative stress in microglia. Methods: Microglia from wild-type (WT) and TRPM2-knockout (KO) mice were exposed to 10-30 mM H2O2 for up to 24 hours. Morphological changes characteristic of microglial activation, [Ca2+]c, ROS generation and the effects of inhibiting particular signalling pathways were examined. Results: Exposure of WT microglia to H2O2 for 24 hours caused no cell death but induced salient morphological changes, which was prevented by TRPM2-KO. Exposure of WT microglia to H2O2 to 2 hours failed, and extension to 8 hours was required, to induce an increase in [Ca2+]c, which was abolished by TRPM2-KO. Exposure of microglia to H2O2 for 8 hours induced ROS generation, which was suppressed by inhibition of PKC and NADPH oxidases (NOX). H2O2-induced PARP activation in TRPM2-KO cells was lower than that in WT cells. Furthermore, H2O2-induced activation of PARP and TRPM2 and morphological changes were attenuated by inhibition of PCK and NOX as well as PYK2 and MEK/ERK. Conclusion: Our results support that PKC/NOX-mediated ROS generation and TRPM2-mediated Ca2+-induced activation of the PYK2/MEK/ERK pathway form a positive feedback mechanism to drive TRPM2 channel activation by non-cytolytic oxidative stress. |
| format | Article |
| id | my.upm.eprints-123003 |
| institution | Universiti Putra Malaysia |
| language | en |
| publishDate | 2025 |
| publisher | Taylor and Francis |
| record_format | eprints |
| spelling | my.upm.eprints-1230032026-02-24T06:31:00Z http://psasir.upm.edu.my/id/eprint/123003/ The PKC/NOX/ROS and PYK2/MEK/ERK/PARP signalling pathways drive TRPM2 channel activation induced by non-cytolytic oxidative stress in microglial cells Syed Mortadza, Sharifah Alawieyah Mohamad Zahir, Nur Zulaikha Wei, Chew Tze Jiang, Lin Hua Objectives: The study aimed to investigate the signalling mechanism for TRPM2 channel activation by non-cytolytic oxidative stress in microglia. Methods: Microglia from wild-type (WT) and TRPM2-knockout (KO) mice were exposed to 10-30 mM H2O2 for up to 24 hours. Morphological changes characteristic of microglial activation, [Ca2+]c, ROS generation and the effects of inhibiting particular signalling pathways were examined. Results: Exposure of WT microglia to H2O2 for 24 hours caused no cell death but induced salient morphological changes, which was prevented by TRPM2-KO. Exposure of WT microglia to H2O2 to 2 hours failed, and extension to 8 hours was required, to induce an increase in [Ca2+]c, which was abolished by TRPM2-KO. Exposure of microglia to H2O2 for 8 hours induced ROS generation, which was suppressed by inhibition of PKC and NADPH oxidases (NOX). H2O2-induced PARP activation in TRPM2-KO cells was lower than that in WT cells. Furthermore, H2O2-induced activation of PARP and TRPM2 and morphological changes were attenuated by inhibition of PCK and NOX as well as PYK2 and MEK/ERK. Conclusion: Our results support that PKC/NOX-mediated ROS generation and TRPM2-mediated Ca2+-induced activation of the PYK2/MEK/ERK pathway form a positive feedback mechanism to drive TRPM2 channel activation by non-cytolytic oxidative stress. Taylor and Francis 2025-05-15 Article PeerReviewed text en cc_by_4 http://psasir.upm.edu.my/id/eprint/123003/1/123003.pdf Syed Mortadza, Sharifah Alawieyah and Mohamad Zahir, Nur Zulaikha and Wei, Chew Tze and Jiang, Lin Hua (2025) The PKC/NOX/ROS and PYK2/MEK/ERK/PARP signalling pathways drive TRPM2 channel activation induced by non-cytolytic oxidative stress in microglial cells. Redox Report, 30 (1). art. no. 2503131. pp. 1-19. ISSN 1351-0002; eISSN: 1743-2928 https://www.tandfonline.com/doi/full/10.1080/13510002.2025.2503131 Biochemistry Physiology 10.1080/13510002.2025.2503131 |
| spellingShingle | Biochemistry Physiology Syed Mortadza, Sharifah Alawieyah Mohamad Zahir, Nur Zulaikha Wei, Chew Tze Jiang, Lin Hua The PKC/NOX/ROS and PYK2/MEK/ERK/PARP signalling pathways drive TRPM2 channel activation induced by non-cytolytic oxidative stress in microglial cells |
| title | The PKC/NOX/ROS and PYK2/MEK/ERK/PARP signalling pathways drive TRPM2 channel activation induced by non-cytolytic oxidative stress in microglial cells |
| title_full | The PKC/NOX/ROS and PYK2/MEK/ERK/PARP signalling pathways drive TRPM2 channel activation induced by non-cytolytic oxidative stress in microglial cells |
| title_fullStr | The PKC/NOX/ROS and PYK2/MEK/ERK/PARP signalling pathways drive TRPM2 channel activation induced by non-cytolytic oxidative stress in microglial cells |
| title_full_unstemmed | The PKC/NOX/ROS and PYK2/MEK/ERK/PARP signalling pathways drive TRPM2 channel activation induced by non-cytolytic oxidative stress in microglial cells |
| title_short | The PKC/NOX/ROS and PYK2/MEK/ERK/PARP signalling pathways drive TRPM2 channel activation induced by non-cytolytic oxidative stress in microglial cells |
| title_sort | pkc/nox/ros and pyk2/mek/erk/parp signalling pathways drive trpm2 channel activation induced by non-cytolytic oxidative stress in microglial cells |
| topic | Biochemistry Physiology |
| url | http://psasir.upm.edu.my/id/eprint/123003/1/123003.pdf http://psasir.upm.edu.my/id/eprint/123003/ https://www.tandfonline.com/doi/full/10.1080/13510002.2025.2503131 |
| url_provider | http://psasir.upm.edu.my/ |