Electron Beam-Induced Sterility and Inhibition of Ovarian Development in the Sakhalin Pine Longicorn, Monochamus saltuarius (Coleoptera: Cerambycidae).

The Sakhalin pine longicorn, Monochamus saltuarius (Gebler; Coleoptera: Cerambycidae), is an insect vector of the pine wilt nematode (PWN), Bursaphelenchus xylophilus (Steiner et Buhrer) Nickle, and is widely distributed in central Korea. M. saltuarius is a forest pest that seriously damages Pinus densiflora (Siebold et Zucc, Pinales: Pinaceae) and Pinus koraiensis (Siebold & Zucc, Pinales: Pinaceae) forests. We examined the effect of electron beam irradiation on the mating, DNA damage and ovarian development of M. saltuarius adults and sought to identify the optimal dose for sterilizing insects. When the adults were irradiated with electron beams, both females and males were completely sterile at 200 Gy. In a reciprocal crossing experiment between unirradiated and irradiated adults, the reproductive ability of wild adults was recovered by crossing with wild adults even after crossing previously with sterile adults. When a pair of unirradiated adults (♀- × â™‚-) and 10 or 20 irradiated adults (♀+ or ♂+) were kept together, the control effect was as high as 80~90%. After electron beam irradiation at 200 Gy, the DNA of M. saltuarius adults was damaged, the ovarian development of female adults was inhibited, and the level of vitellogenin was significantly decreased compared with that in unirradiated female adults. These results suggest that pine wilt disease can be effectively controlled if a large number of sterilized M. saltuarius male adults are released into the field.

B7-H4 downregulation induces mitochondrial dysfunction and enhances doxorubicin sensitivity via the cAMP/CREB/PGC1-α signaling pathway in HeLa cells.

B7-H4 is a B7 family coregulatory protein that inhibits T cell-mediated immunity. B7-H4 is overexpressed in various cancers; however, the functional role of B7-H4 in cancer metabolism is poorly understood. Because mitochondria play pivotal roles in development, proliferation, and death of cancer cells, we investigated molecular and functional alterations of mitochondria in B7-H4-depleted HeLa cells. In a human study, overexpression of B7-H4 was confirmed in the cervices of adenocarcinoma patients (n = 3) compared to noncancer patients (n = 3). In the cell line model, B7-H4 depletion was performed by transfection with small interfering RNA (siRNA). B7-H4 depletion suppressed oxygen consumption rate, ATP production, and mitochondrial membrane potential and mass and increased reactive oxygen species production. In particular, electron transport complex III activity was significantly impaired in siB7-H4-treated cells. Coincidently, depletion of B7-H4 suppressed major mitochondrial regulators (peroxisome proliferator-activated receptor gamma coactivator 1-alpha [PGC1-α] and mitochondrial transcription factor A), a component of oxidative phosphorylation (ubiquinol-cytochrome c reductase core protein 1), and an antiapoptosis protein (Bcl-XL). Mitochondrial dysfunction in siRNA-treated cells significantly augmented oxidative stress, which strongly activated the JNK/P38/caspase axis in the presence of doxorubicin, resulting in increased apoptotic cell death. Investigating the mechanism of B7-H4-mediated mitochondrial modulation, we found that B7-H4 depletion significantly downregulated the cAMP/cAMP response element-binding protein/PGC1-α signaling pathway. Based on these findings, we conclude that B7-H4 has a role in the regulation of mitochondrial function, which is closely related to cancer cell physiology and drug sensitivity.