Nitric oxide damages neuronal mitochondria and induces apoptosis in neurons

The cytotoxic effect of nitric oxide on primarily cultured rat cerebellar granule cells was stuatea, and the mechanisms were discussed. The results showed that nitric oxide donor S-nitroso-N-acetyl-penicillamine (SNAP; 500 (imol/L) could induce apoptosis in immature cultures of cerebellar granule cells. Flow cytometry and HPLC analyses revealed that after treatment with SNAP, the mitochondrial transmembrane potential and the cellular ATP content decreased significantly. Nitric oxide scavenger hemoglobin could effectively prevent the neuronal mitochondria from dysfunction and attenuate apoptosis. The results suggested that nitric oxide activated the apoptotic program by inhibiting the activity of mitochondrial respiratory chain and thus decreasing the cellular ATP content.

Plasma membrane calcium ATPase 4b inhibits nitric oxide generation through calcium-induced dynamic interaction with neuronal nitric oxide synthase

The activation and deactivation of Ca^(2+)- and calmodulindependent neuronal nitric oxide synthase (nNOS) in the central nervous system must be tightly controlled to prevent excessive nitric oxide (NO) generation. Considering plasma membrane calcium ATPase (PMCA) is a key deactivator of nNOS, the present investigation aims to determine the key events involved in nNOS deactivation of by PMCA in living cells to maintain its cellular context. Using time-resolved Förster resonance energy transfer (FRET), we determined the occurrence of Ca^(2+)-induced protein-protein interactions between plasma membrane calcium ATPase 4b (PMCA4b) and nNOS in living cells. PMCA activation significantly decreased the intracellular Ca 2+ concentrations ([Ca^(2+)]_(i)), which deactivates nNOS and slowdowns NO synthesis. Under the basal [Ca^(2+)]_(i) caused by PMCA activation, no protein-protein interactions were observed between PMCA4b and nNOS. Furthermore, both the PDZ domain of nNOS and the PDZ-binding motif of PMCA4b were essential for the protein-protein interaction. The involvement of lipid raft microdomains on the activity of PMCA4b and nNOS was also investigated. Unlike other PMCA isoforms, PMCA4 was relatively more concentrated in the raft fractions. Disruption of lipid rafts altered the intracellular localization of PMCA4b and affected the interaction between PMCA4b and nNOS, which suggest that the unique lipid raft distribution of PMCA4 may be responsible for its regulation of nNOS activity. In summary, lipid rafts may act as platforms for the PMCA4b regulation of nNOS activity and the transient tethering of nNOS to PMCA4b is responsible for rapid nNOS deactivation.

Lysosomal chymotrypsin induces mitochondrial fission in apoptotic cells by proteolytic activation of calcineurin

Dear Editor Apoptosis is a fundamental physiological process in mam- mals in which cells die by activating a suicide mechanism. The mitochondria are one of the major checkpoints in apoptotic regulation because they serve as sensors and amplifiers of cellular damage （Green and Kroemer, 2004）. After mitochondrial outer membrane permeabilization （MOMP）, the mitochondria release a number of factors that are critically involved in cell death signaling （Tait and Green, 2010）. Bcl-2 family members are regarded as the key reg- ulators of mitochondria-dependent apoptosis （Moldoveanu et al., 2014）; however, dynamin-related protein 1 （Drpl）, which orchestrates mitochondrial fission, also participates in apoptotic regulation by stimulating Bax oligomerization and thereby enhances MOMP （Montessuit et al., 2010）; accord- ingly, the inhibition of Drpl blocks mitochondrial fission and inhibits apoptosis （Cassidy-Stone et al., 2008）.

Identification of lipid droplets in gut bacteria

Dear Editor,The field of gut microbiota is progressing rapidly and thus,appellations like the last human organ,a separate organ,a forgotten organ,and a new organ have been applied to gut microbiota to emphasize its vital functions in our body(Chang and Kao,2019).Gut microbiota has been shown to play a central role in the regulation of human lipid metabolism and be associated with lipid metabolism disorders when aberrant,through composition and microbial metabolites.

Phorbol myristate acetate suppresses breast cancer cell growth via down-regulation of P-Rex1 expression

Dear Editor,P-Rex1 is a Rac-selective guanine nucleotide exchange factor （GEF） that is synergistically activated by G-protein coupled receptors and receptor tyrosine kinases （Welch et al., 2002）. We previously reported that aberrantly upreg- ulated P-Rex1 promotes prostate cancer metastasis by activating Racl signals （Qin et al., 2009）.