ABSTRACT
Interleukin (IL)-32 is induced by pro-inflammatory cytokines and promotes the release of inflammatory cytokines. Therefore, it can promote inflammatory responses. The present review article summarized the role of the receptors required for IL-32 action, the biological function of IL-32 and its mechanism of action in tumors. Moreover, it assessed the significance of aberrant IL-32 expression in associated diseases and analyzed the effects of IL-32 on four key types of cancer: Colorectal, gastric, breast and lung. However, the mechanism of action of IL-32 needs to be further demonstrated by assessing the role of this cytokine in cancer to elucidate novel and reliable targets for future cancer treatments.
ABSTRACT
The histone demethylase JMJD family is involved in various physiological and pathological functions. However, the roles of JMJD1A in the cardiovascular system remain unknown. Here, we studied the function of JMJD1A in cardiac hypertrophy. The mRNA and protein levels of JMJD1A were significantly downregulated in the hearts of human patients with hypertrophic cardiomyopathy and the hearts of C57BL/6 mice underwent cardiac hypertrophy induced by transverse aortic constriction (TAC) surgery or isoproterenol (ISO) infusion. In neonatal rat cardiomyocytes (NRCMs), siRNA-mediated JMJD1A knockdown facilitated ISO or angiotensin II-induced increase in cardiomyocyte size, protein synthesis, and expression of hypertrophic fetal genes, including atrial natriuretic peptide (Anp), brain natriuretic peptide (Bnp), and Myh7. By contrast, overexpression of JMJD1A with adenovirus repressed the development of ISO-induced cardiomyocyte hypertrophy. We observed that JMJD1A reduced the production of total cellular and mitochondrial levels of reactive oxygen species (ROS), which was critically involved in the effects of JMJD1A because either N-acetylcysteine or MitoTEMPO treatment blocked the effects of JMJD1A deficiency on cardiomyocyte hypertrophy. Mechanism study demonstrated that JMJD1A promoted the expression and activity of Catalase under basal condition or oxidative stress. siRNA-mediated loss of Catalase blocked the protection of JMJD1A overexpression against ISO-induced cardiomyocyte hypertrophy. These findings demonstrated that JMJD1A loss promoted cardiomyocyte hypertrophy in a Catalase and ROS-dependent manner.
Subject(s)
Cardiomegaly , Catalase/metabolism , Jumonji Domain-Containing Histone Demethylases/metabolism , Myocytes, Cardiac , Animals , Cardiomegaly/metabolism , Cardiomegaly/pathology , Catalase/genetics , Cells, Cultured , Jumonji Domain-Containing Histone Demethylases/genetics , Mice , Mice, Inbred C57BL , Myocardium/cytology , Myocardium/metabolism , Myocardium/pathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Reactive Oxygen Species/metabolismABSTRACT
MicroRNA plays an important role in gastric cancer (GC) development, while the function of miR-497-5p in this disease remains unknown. In the present study, we demonstrated miR-497-5p as a tumor suppressive microRNA in GC. miR-497-5p was down-regulated in GC tissues and its expression was associated with the disease stage. Inhibition of miR-497-5p promoted GC cell proliferation and growth. By contrast, miR-497-5p ectopic expression suppressed the proliferation and growth of GC cells. In addition, miR-497-5p inhibited DNA synthesis and enhanced apoptosis in GC cells. The cell cycle progression was suppressed by miR-497-5p. Mechanistically, miR-497-5p directly targeted and suppressed the expression of pyruvate dehydrogenase kinase 3 (PDK3), which is highly expressed in GC tissues. Over-expression of PDK3 promoted the proliferation of GC cells. Our study revealed that miR-497-5p inhibited GC cell proliferation and growth via targeting PDK3.
Subject(s)
MicroRNAs/genetics , Pyruvate Dehydrogenase Acetyl-Transferring Kinase/genetics , Stomach Neoplasms/pathology , Aged , Apoptosis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Disease Progression , Gene Expression Regulation, Neoplastic , Genes, Tumor Suppressor , Humans , Middle Aged , RNA Interference , RNA, Small Interfering/genetics , Signal Transduction , Stomach Neoplasms/geneticsABSTRACT
Betulinic acid (BA) is a naturally occurring pentacyclic lupane group triterpenoid, has reported to protect cerebral ischemia. Present study evaluates the protective effect of betulinic acid on the isoflurane-induced neuronal damage in neonatal mice. All the mice of 7days age were exposed to isoflurane (2%; 2h) for the duration of 3day. At the end of protocol cognitive function was evaluated by Morris water maze (MWM) test. However count of apoptotic cells were estimated by TUNEL staining. Concentration of oxidative stress parameters [superoxide dismutase (SOD); catalase (CAT) and reduced glutathione (GSH)], cytokines [tumor necrosis factor (TNF-α); interlukin-6 (IL-6) and IL-1ß] and expressions of caspase 3, FAS and FASL were estimated in the neuronal cells. Result of the study suggested that treatment with betulinic acid significantly reduces the escape latency and enhances platform crossing time than negative control group. Count of apoptotic cells were also found to be reduced in BA treated group of mice than negative control group. Moreover treatment with BA significantly attenuates the concentration of inflammatory cytokines and oxidative stress in isoflurane induced neonatal mice. However expressions of caspase-3, FAS/FASL was found to be significantly reduced in BA treated group of mice than negative control group. Present study concludes the neuroprotective effect of betulinic acid in isoflurane-induced brain damage in developing brain by attenuating the apoptosis through Fas/FASL pathway inhibition.
