AMP-activated protein kinase-dependent autophagy mediated the protective effect of sonic hedgehog pathway on oxygen glucose deprivation-induced injury of cardiomyocytes.

Sonic hedgehog (Shh) pathway has been reported to protect cardiomyocytes in myocardial infarction (MI), but the underlying mechanism is not clear. Here, we provide evidence that Shh pathway induces cardiomyocytes survival through AMP-activated protein kinase-dependent autophagy. Shh pathway agonist SAG increased the expression of LC3-II, and induced the formation of autophagosomes in cultured H9c2 cardiomyocytes under oxygen glucose deprivation (OGD) 1 h and 4 h. Moreover, SAG induced a profound AMP-activated protein kinase (AMPK) activation, and then directly phosphorylated and activated the downstream autophagy initiator Ulk1, independent of the autophagy suppressor mammalian target of rapamycin (mTOR) complex 1. Taken together, our results have shown that Shh activates AMPK-dependent autophagy in cardiomyocytes under OGD, suggesting a role of autophagy in Shh-induced cellular protection.

Expression and biological significance of human kallikrein 6 in gastric cancer tissues.

AIM OF THE STUDY: This study aims to investigate the expression of human kallikrein 6 (hK6) in gastric cancer, gastric ulcer and normal gastric mucosa tissues and its biological significance. MATERIAL AND METHODS: The expression of hK6 in 15 normal gastric mucosa (NGM) tissues, 15 gastric ulcer (GU) tissues and 55 gastric carcinoma (GC) tissues was respectively detected by immunohistochemistry. The correlations between the expression of hK6 and the clinical pathological parameters of gastric cancer were also analyzed. RESULTS: Human kallikrein 6 was mainly expressed in cytoplasm. The positive rate of hK6 was significantly higher in gastric cancer tissues than that in gastric ulcer or normal gastric mucosa tissues (70.9%, 40% and 20%, respectively, p < 0.01). With the increase of the invasion depth of gastric cancer cells, aggravation of TNM stage and development of lymph node metastasis, the expression of hK6 increased significantly (p < 0.05 and p < 0.01). There was no obvious correlation between the expression of hK6 and sex, age, tumor diameter, histodifferentiation degree or primary pathological location of gastric cancer (p > 0.05). CONCLUSIONS: The overexpression of hK6 is related to the depth of invasion, lymph node metastasis and clinical stage of gastric carcinoma, which suggests that hK6 may act as a new marker of gastric cancer biological behavior.