Maprotiline Ameliorates High Glucose-Induced Dysfunction in Renal
                    Glomerular Endothelial Cells

Zhihong Zhou; Shangjun Liu

doi:10.1055/a-1713-7719

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2022; 130(09): 596-603
DOI: 10.1055/a-1713-7719

Article

Maprotiline Ameliorates High Glucose-Induced Dysfunction in Renal Glomerular Endothelial Cells

Zhihong Zhou^*

¹Department of Geriatrics, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou City, Hainan Province, China

,

Shangjun Liu^*

²Department of Cardiovascular Medicine, Sanya Central Hospital (Hainan Third People’s Hospital), Sanya City, Hainan Province, China

› Author Affiliations

Abstract

Maprotiline is an antidepressant that has been found to cause hypoglycemia. However, the effect of maprotiline on diabetic nephropathy (DN) has not been investigated. Here, we explored the effect of maprotiline on human renal glomerular endothelial cells (HRGECs) in response to high glucose (HG) stimulation. We found that maprotiline attenuated HG-induced oxidative stress in HRGECs with decreased reactive oxygen species production and increased superoxide dismutase activity. Maprotiline repressed the HG-induced expression of cyclooxygenases 2 at both mRNA and protein levels in HRGECs. The increased thromboxane B2 level and decreased 6-keto-prostaglandin F1α level induced by HG were significantly attenuated by maprotiline treatment. Maprotiline also prevented the HG-induced increase in the permeability of HRGECs and the decrease in the zonula occludens-1 expression and downregulated HG-induced increase in the expression of protein kinase C-α (PKC-α) in HRGECs. This protective effect of maprotiline on HG-induced HRGECs dysfunction was abolished by overexpression of PKC-α. In conclusion, maprotiline displayed a protective effect on HG-challenged HRGECs, which was mediated by the regulation of PKC-α. These findings provide further evidence for the potential use of maprotiline for the treatment of DN.

Key words

Maprotiline - diabetic nephropathy (DN) - oxidative stress - inflammation - permeability - protein kinase C (PKC)

Full Text

References

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