MiRNAs participate in the regulation of apoptosis. However, it remains largely unknown as to how miRNAs are integrated into the apoptotic program. Mitochondrial fission is involved in the initiation of apoptosis. It is not yet clear whether miRNAs are able to regulate mitochondrial fission. Here we report that miR-30 family members are able to regulate apoptosis by targeting the mitochondrial fission machinery. Our data show that miR-30 family members can inhibit mitochondrial fission and the consequent apoptosis. In exploring the underlying molecular mechanism, we identified that miR-30 family members can suppress p53 expression. In response to the apoptotic stimulation, the expression levels of miR-30 family members were reduced, whereas p53 was upregulated. p53 transcriptionally activated the mitochondrial fission protein, dynamin-related protein-1 (Drp1). The latter conveyed the apoptotic signal of p53 by initiating the mitochondrial fission program. miR-30 family members inhibited mitochondrial fission through suppressing the expression of p53 and its downstream target Drp1. Our data reveal a novel model in which a miRNA can regulate apoptosis through targeting the mitochondrial fission machinery. Apoptosis is related to the pathogenesis of many diseases such as tumors and neurodegenerative and cardiovascular disorders. Apoptosis is controlled by a variety of genes, and among them a protein called “p53” has been taken as a “death star” and is involved in the initiation of apoptosis. The upstream and downstream molecules that control and convey p53 apoptotic function remain to be further identified. MicroRNAs (miRNAs) are a class of small non-coding RNAs that mediate post-transcriptional gene silencing. Mitochondrial fission participates in the initiation of apoptosis and requires the activation of a protein called dynamin-related protein-1 (Drp1). Our present work has revealed that miR-30 can target p53, thereby inhibiting p53 expression. Furthermore, our data show that p53 is able to induce mitochondrial fission by transcriptionally regulating Drp1. In addition, miR-30 controls Drp1 activity and the consequent apoptosis through p53. Our findings may warrant future studies to explore the therapeutic approaches for apoptosis-related diseases by targeting the miR-30-p53-Drp1 pathway.

MicroRNAs (miRNAs) are a class of small noncoding RNAs that mediate posttranscriptional gene silencing. Mitochondrial fission participates in the induction of apoptosis. It remains largely unknown whether miRNAs can regulate mitochondrial fission. Reactive oxygen species and doxorubicin could induce mitochondrial fission and apoptosis in cardiomyocytes. Concomitantly, mitofusin 1 (Mfn1) was downregulated, whereas miRNA 140 (miR-140) was upregulated upon apoptotic stimulation. We investigated whether Mfn1 and miR-140 play a functional role in mitochondrial fission and apoptosis. Ectopic expression of Mfn1 attenuated mitochondrial fission and apoptosis. Knockdown of miR-140 inhibited mitochondrial fission. Our results further revealed that knockdown of miR-140 was able to reduce myocardial infarct sizes in an animal model. We observed that miR-140 could suppress the expression of Mfn1, and it exerted its effect on mitochondrial fission and apoptosis through targeting Mfn1. Our data revealed that mitochondrial fission occurs in cardiomyocytes and can be counteracted by Mfn1. However, the function of Mfn1 is negatively regulated by miR-140. Our present work suggests that Mfn1 and miR-140 are integrated into the program of cardiomyocyte apoptosis.

Background— Apoptosis repressor with caspase recruitment domain (ARC) is abundantly expressed in cardiomyocytes. Protein kinase CK2 can phosphorylate ARC at threonine-149, thereby enabling ARC to antagonize apoptosis. ARC phosphorylation occurs in a constitutive manner. Nevertheless, cardiomyocytes still undergo apoptosis that is related to cardiac diseases such as myocardial infarction and heart failure. Whether the occurrence of apoptosis is related to the loss of protection by ARC under pathological conditions remains unknown. Methods and Results— ARC phosphorylation levels are decreased in cardiomyocytes treated with isoproterenol or aldosterone. We explored the molecular mechanism by which ARC phosphorylation levels are decreased. Our results reveal that either direct incubation or coexpression with calcineurin leads to a decrease in ARC phosphorylation levels. Inhibition of calcineurin can attenuate the reduction in ARC phosphorylation levels on treatment with isoproterenol or aldosterone. These data indicate that the reduction in ARC phosphorylation levels is related to its dephosphorylation by calcineurin. Our results further reveal that ARC can prevent isoproterenol- and aldosterone-induced apoptosis, but this function depends on its phosphorylation status. Isoproterenol and aldosterone upregulate Fas ligand expression, and Fas ligand and caspase-8 are required for isoproterenol and aldosterone to induce apoptosis. However, phosphorylated but not dephosphorylated ARC is able to inhibit caspase-8–mediated apoptosis. Phosphorylated ARC exerts its effects against caspase-8 by directly associating with procaspase-8 and inhibiting its interaction with Fas-associated protein with death domain. Conclusions— Our study identifies a novel cardiac apoptotic pathway in which ARC is dephosphorylated by calcineurin. This pathway could be a component in the cardiac apoptotic machinery.

A lectin designated asHericium erinaceumagglutinin (HEA) was isolated from dried fruiting bodies of the mushroomHericium erinaceumwith a chromatographic procedure which entailed DEAE-cellulose, CM-cellulose, Q-Sepharose, and FPLC Superdex 75. Its molecular mass was estimated to be 51 kDa and its N-terminal amino acid sequences was distinctly different from those of other isolated mushroom lectins. The hemagglutinating activity of HEA was inhibited at the minimum concentration of 12.5 mM by inulin. The lectin was stable at pH 1.9–12.1 and at temperatures up to C, but was inhibited by , , and ions. The lectin exhibited potent mitogenic activity toward mouse splenocytes, and demonstrated antiproliferative activity toward hepatoma (HepG2) and breast cancer (MCF7) cells with an of 56.1 M and 76.5 M, respectively. It manifested HIV-1 reverse transcriptase inhibitory activity with an of 31.7 M. The lectin exhibited potent mitogenic activity toward murine splenocytes but was devoid of antifungal activity.