Exp Clin Endocrinol Diabetes 2021; 129(06): 420-428
DOI: 10.1055/a-0919-4489
Article

Dimethyloxalylglycine (DMOG) and the Caspase Inhibitor “Ac-LETD-CHO” Protect Neuronal ND7/23 Cells of Gluocotoxicity

Debasmita Mukhopadhyay
1   Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates
,
Mohammad Hammami
1   Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates
,
Amani Khalouf
1   Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates
,
Yazan Al Shaikh
1   Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates
,
Abdul Khader Mohammed
1   Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates
,
Mawieh Hamad
1   Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates
,
Albert Salehi
2   Department of Clinical Science, Division of Islet Cell Physiology, Lund University, Malmö, Sweden
,
Jalal Taneera
1   Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates
› Author Affiliations

Abstract

It well known that long-lasting hyperglycaemia disrupts neuronal function and leads to neuropathy and other neurodegenerative diseases. The α-ketoglutarate analogue (DMOG) and the caspase-inhibitor “Ac-LETD-CHO are potential neuroprotective molecules. Whether their protections may also extend glucotoxicity-induced neuropathy is not known. Herein, we evaluated the possible cell-protective effects of DMOG and Ac-LETD-CHO against hyperglycaemia-induced reactive oxygen species and apoptosis in ND7/23 neuronal cells. The impact of glucotoxicity on the expression of HIF-1α and a panel of micro-RNAs of significance in hyperglycaemia and apoptosis was also investigated.

ND7/23 cells cultured under hyperglycaemic conditions showed decreased cell viability and elevated levels of ROS production in a dose- and time-dependent manner. However, presence DMOG (500 µM) and/or Ac-LETD-CHO (50 µM) counteracted this effect and increase cell viability concomitant with reduction in ROS production, DNA damage and apoptosis. AcLETD-CHO suppressed hyperglycaemia-induced caspase 3 activation in ND7/23 cells. Both DMOG and Ac-LETD-CHO increased HIF-1α expression paralleled with the suppression of miR-126–5p, miR-128–3p and miR-181 expression and upregulation of miR-26b, 106a-5p, 106b-5p, 135a-5p, 135b-5p, 138–5p, 199a-5p, 200a-3p and 200c-3p expression.

We demonstrate a mechanistic link for the DMOG and Ac-LETD-CHO protection against hyperglycaemia-induced neuronal dysfunction, DNA damage and apoptosis and thereby propose that pharmacological agents mimicking these effects may represent a promising novel therapy for the hyperglycaemia-induced neuropathy.



Publication History

Received: 30 January 2019
Received: 28 March 2019

Accepted: 14 May 2019

Article published online:
11 June 2019

© 2019. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
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