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Role of the PKCβII/JNK signaling pathway in acute glucose fluctuation-induced apoptosis of rat vascular endothelial cells
- Source :
- Acta Diabetologica. 54:727-736
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- The purpose of this study was to investigate the mechanism of vascular endothelial cell apoptosis induced by acute blood glucose fluctuation.Thirty rats were assigned to three groups: normal saline (SAL group), constant high glucose (CHG group) and acute blood glucose fluctuation (AFG) group. Other forty rats were assigned to SAL group, AFG group, LY group (PKCβ inhibitor LY333531 was injected intragastrically to the rats who were under acute blood glucose fluctuation) and SP group (JNK inhibitor SP600125 was injected intraperitoneally to the rats who were under acute blood glucose fluctuation). Oxidative stress and inflammatory cytokines were detected. TUNEL was performed to detect apoptosis. Pro-caspase-3, caspase-3 p17, JNK, PKC-βII and insulin signaling-related protein expression were tested by Western blotting.After administration of LY333531, AFG-induced membrane translocation of PKCβII protein was inhibited, but SP600125 failed to affect AFG-induced PKCβII membrane translocation. After administration of LY333531, the AFG-induced increase in JNK activity was significantly compromised. LY333531 inhibited AFG-induced oxidative stress. However, SP600125 only slightly inhibited AFG-induced oxidative stress reaction (P 0.05). Both LY333531 and SP600125 can reverse AFG-induced endothelial cell apoptosis increase, inflammatory cytokines levels rise and insulin signaling impairment.It is necessary to actively control blood glucose and avoid significant glucose fluctuation. PKCβII/JNK may serve as a target, and inhibitors of PKCβII/JNK may be used to help prevent cardiovascular diseases in patients with poor glucose control or significant glucose fluctuation.
- Subjects :
- Male
MAP Kinase Kinase 4
MAP Kinase Signaling System
Endocrinology, Diabetes and Metabolism
Apoptosis
030209 endocrinology & metabolism
Inflammation
030204 cardiovascular system & hematology
medicine.disease_cause
03 medical and health sciences
0302 clinical medicine
Endocrinology
Diabetes mellitus
Protein Kinase C beta
Internal Medicine
medicine
Endothelial cell apoptosis
Animals
Humans
JNK signaling pathway
Rats, Wistar
Caspase 3
Mechanism (biology)
Chemistry
Endothelial Cells
General Medicine
medicine.disease
Rats
Cell biology
Oxidative Stress
Glucose
medicine.symptom
Oxidative stress
Subjects
Details
- ISSN :
- 14325233 and 09405429
- Volume :
- 54
- Database :
- OpenAIRE
- Journal :
- Acta Diabetologica
- Accession number :
- edsair.doi.dedup.....5571786798c34835537062c6163d98fa