ABSTRACT
To explore the protective effect of naringin(Nar) on the injury of myocardium tissues induced by streptozotocin(STZ) in diabetic rats and the relationship with oxidative stress and endoplasmic reticulum stress(ERS)ï¼ the male SD rats were intraperitoneally injected with streptozotocin(STZï¼ 60 mg·kg⻹) to establish the diabetic rat model and then randomly divided into the type 1 diabetic rat group(T1DR)ï¼ the low-dose Nar group(Nar25)ï¼ the middle-dose Nar group(Nar50) and the high-dose Nar group(Nar100). The normal rats were designed as control group(Con). Nar25ï¼ Nar50ï¼ Nar100 groups were orally administered with Nar at the doses of 25.0ï¼ 50.0ï¼ 100.0 mg·kg⻹ per dayï¼ respectivelyï¼ while the normal group and the T1DR group were orally administered with saline. At the 8th week after treatmentï¼ fasting plasma glucose and heart mass index were measured. The pathological changes in myocardial tissues were observed by microscope. The cardiac malondialdehyde(MDA) level and superoxide dismutase(SOD) activities were measured. The gene and protein expressions of glucose-regulated protein 78(GRP78)ï¼ C/EBP homologous protein(CHOP)ï¼ cysteinyl aspartate-specific proteinase 12(caspase 12) were detected by qRT-PCR and Western blot. According to the resultsï¼ compared with control groupï¼ the myocardial structure was damagedï¼ the content of MDA was increasedï¼ while the activities of SOD were decreased(P<0.05) in T1DR group. GRP78ï¼ CHOP and caspase 12 mRNA and protein expressions were increased significantly in T1DR group(P<0.05ï¼ P<0.01). Compared with T1DR groupï¼ myocardial structure damage was alleviated in Nar treatment group. The content of MDA was decreasedï¼ while the activities of SOD were increased significantly. The mRNA and protein expressions of GRP78ï¼ CHOP and caspase 12 were increasedï¼ especially in middle and high-dose groups(P<0.05ï¼ P<0.01). After treatment with Nar for 8 weeksï¼ myocardial structure damage was obviously alleviated in Nar treatment groups. The content of MDA was decreasedï¼ while the activities of SOD were increased significantly in myocardial tissues. The mRNA and protein expressions of GRP78ï¼ CHOP and caspase 12 were increasedï¼ especially in middle and high-dose groups(P<0.05ï¼ P<0.01). The findings suggest that Nar may protect myocardium in diabetic rats by reducing mitochondrial oxidative stress injuries and inhibiting the ERS-mediated cell apoptosis pathway.
Subject(s)
Cardiotonic Agents/pharmacology , Diabetic Cardiomyopathies/drug therapy , Endoplasmic Reticulum Stress/drug effects , Flavanones/pharmacology , Oxidative Stress/drug effects , Animals , Apoptosis , Caspase 12/metabolism , Diabetes Mellitus, Experimental , Heat-Shock Proteins/metabolism , Male , Malondialdehyde/metabolism , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism , Transcription Factor CHOP/metabolismABSTRACT
Taxol is a precious and effective anticancer drug. Cerium and methyl jasmonate (MJ) have been shown to increase the yield of taxol in taxus cells. However, the mechanisms of cerium-mediated and MJ-mediated taxol biosynthesis remain unknown. RNA-Seq was applied to study the overall regulation mechanism of cerium and MJ on taxol biosynthesis and analyze the differences among T. mairei cells elicited by Ce3+, Ce4+ and MJ on transcriptional level . Using sequence homology, 179 unigenes were identified as taxol synthesis genes. Under the condition of 100 µM MJ, taxol synthesis genes were up-regulated. Notably, taxol synthesis genes were down-regulated expression at 1 mM Ce3+ and 1 mM Ce4+. Differential expression genes involved in some related functions were analyzed, such as MAPK signaling pathway and plant-pathogen interaction. Sequence alignment and phylogenetic analysis of nine differentially expressed WRKYs in our data were carried out.