Heme oxygenase-1 enhances autophagy in podocytes as a protective mechanism against High glucose-induced apoptosis.

Heme oxygenase-1 enhances autophagy in podocytes as a protective mechanism against High glucose-induced apoptosis. Exp Cell Res. 2015 Apr 13; Authors: Dong C, Zheng H, Huang S, You N, Xu J, Ye X, Zhu Q, Feng Y, You Q, Miao H, Ding D, Lu Y Abstract Injury and loss of podocytes play vital roles in diabetic nephropathy progression. Emerging evidence suggests autophagy, which is induced by multiple stressors including hyperglycemia, plays a protective role. Meanwhile, heme oxygenase-1 (HO-1) possesses powerful anti-apoptotic properties. Therefore, we investigated the impact of autophagy on podocyte apoptosis under diabetic conditions and its association with HO-1. Mouse podocytes were cultured in vitro; apoptosis was detected by flow cytometry. Transmission electron microscopy and biochemical autophagic flux assays were used to measure the autophagy markers microtubule-associated protein 1 light chain 3-II (LC3-II) and beclin-1. LC3-II and beclin-1 expression peaked 12-24h after exposing podocytes to high glucose. Inhibition of autophagy with 3-methyladenine or Beclin-1 siRNAs or Atg 5 siRNAs sensitized cells to apoptosis, suggesting autophagy is a survival mechanism. HO-1 inactivation inhibited autophagy, which aggravated podocyte injury in vitro. Hemin-induced autophagy also protected podocytes from hyperglycemia in vitro and was abrogated by HO-1 siRNA. Adenosine monophosphate-activated protein kinase phosphorylation was higher in hem...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research