Interplay between the Notch and PI3K/Akt pathways in high glucose-induced podocyte apoptosis.
Podocyte apoptosis contributes to the pathogenesis of diabetic nephropathy (DN). However, the mechanisms that mediate high glucose (HG)-induced podocyte apoptosis remain poorly understood. Conditionally immortalized mouse podocytes were cultured in HG medium. A chemical inhibitor or a specific short-hairpin RNA (shRNA) vector was used to inhibit the activation of the Notch pathway and the PI3K/Akt pathway in HG-treated podocytes. Western blotting and real-time PCR were used to evaluate the levels of Notch, PI3K/Akt, and apoptotic pathway signaling. The apoptosis rate of HG-treated podocytes was assessed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling and annexin V/propidium iodide staining. In HG-treated podocytes, PI3K/Akt pathway activation prevented podocyte apoptosis in the early stage of HG stimulation and Notch pathway-induced podocyte apoptosis in the late stage of HG stimulation. The inhibition of the Notch pathway or the activation of the PI3K/Akt pathway prevented cell apoptosis in HG-treated podocytes. These findings suggest that the Notch and PI3K/Akt pathways may mediate HG-induced podocyte apoptosis.
Dept. of Pathology, Third Hospital, Hebei Medical Univ., No. 139 Ziqiang Rd., Shijiazhuang, Hebei, China 050051. alan846829@163.com.
Xiao-Mei
XM
Wang
Min
M
Yao
Shu-Xia
SX
Liu
Jun
J
Hao
Qing-Juan
QJ
Liu
Feng
F
Gao
D000818:Animals; D017304:Annexin A5; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005822:Genetic Vectors; D005947:Glucose / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D050199:Podocytes / Q000187:drug effects* / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051881:Receptor, Notch1 / Q000378:metabolism / Q000502:physiology; D051880:Receptors, Notch / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects
D017304:Annexin A5; D051017:Apoptosis Regulatory Proteins; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; C497762:Notch1 protein, mouse; D009842:Oligopeptides; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; D051880:Receptors, Notch; C523462:benzyloxycarbonyl-leucyl-leucyl-norleucinal; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D005947:Glucose
Notch pathway; PI3K/Akt pathway; apoptosis; high glucose; podocytes