Family with sequence similarity 134 member B-mediated reticulophagy ameliorates hepatocyte apoptosis induced by dithiothreitol

BACKGROUND Endoplasmic reticulum(ER)stress-related hepatocyte apoptosis is responsible for multiple hepatic diseases.Previous studies have revealed that endoplasmic reticulophagy(ER-phagy)promotes the selective clearance of damaged ER fragments during ER stress,playing a crucial role in maintaining ER homeostasis and inhibiting apoptosis.Family with sequence similarity 134 member B(FAM134B)is a receptor involved in ER-phagy that can form a complex with calnexin(CNX)and microtubule-associated protein 1 light chain 3(LC3).The complex can mediate the selective isolation of ER fragments to attenuate hepatocyte apoptosis.However,the precise regulatory mechanisms remain unclear.AIM To elucidate the effect of FAM134B-mediated ER-phagy on ER stress-induced apoptosis in buffalo rat liver 3A(BRL-3A)rat hepatocytes and the potential regulatory mechanisms.METHODS ER stress-related hepatocyte apoptosis was induced using dithiothreitol(DTT).Proteins related to ER stress and autophagy were measured with western blotting.Protein complex interactions with FAM134B were isolated by co-immunoprecipitation.ER-phagy was evaluated in immunofluorescence experiments.Cell cycle distribution and apoptosis were measured by flow cytometry.Mitochondrial Ca^(2+) levels were evaluated by the co-localization of intracellular Ca^(2+)-tracker and Mitotracker.The small interfering RNA against FAM134B was used to knockdown FAM134B in BRL-3A cells.RESULTS ER stress-related and autophagy-related proteins in BRL-3A cells were elevated by both short and long-term DTT treatment.Furthermore,co-immunoprecipitation confirmed an interaction between FAM134B,CNX,FAM134B,and LC3 in BRL-3A cells.Immunofluorescence assays revealed that autolysosomes significantly decreased following short-term DTT treatment,but increased after long-term treatment.Mitochondrial Ca2+levels and apoptotic rates were dramatically elevated,and more cells were arrested in the G1 stage after short-term DTT treatment;however,these decreased 48 h later.Moreover,FAM134B downregulation accelerated mitochondrial apoptotic pathway activation and aggravated hepatocyte apoptosis under ER stress.CONCLUSION FAM134B-mediated ER-phagy attenuates hepatocyte apoptosis by suppressing the mitochondrial apoptotic pathway.Our findings provide new evidence highlighting the importance of FAM134Bmediated ER-phagy in attenuating hepatocyte apoptosis.

A LARGE CLASS OF BINARY ZCZ SEQUENCE FAMILIES CONSTRUCTED BY PERIOD DOUBLING

In an Approximately Synchronized Code Division Multiple Access (AS-CDMA) commu-nication system,a family with large number of Zero Correlation Zone (ZCZ) sequences is desired,which can satisfy the rapid increase of users. This paper presents a method to generate a (2L ,2M ,Zc' z )-ZCZsequence family from an original (L ,M ,Z cz)-ZCZsequence family,where Z c' z =Zcz if Z czis even and Z c' z = Zcz 1if Z czis odd. This method can also recursively act on a ZCZ sequence family to construct a series of ZCZ sequence families with large sequence number and zero correlation zone length identical to or one less than that of original ZCZ sequences.

Systems Approaches to Biology and Disease Enable Translational Systems Medicine

The development and application of systems strategies to biology and disease are transforming medical research and clinical practice in an unprecedented rate. In the foreseeable future, clinicians, medical researchers, and ultimately the consumers and patients will be increasingly equipped with a deluge of personal health information, e.g., whole genome sequences, molecular profiling of diseased tissues, and periodic multi-analyte blood testing of biomarker panels for disease and wellness. The convergence of these practices will enable accurate prediction of disease susceptibility and early diagnosis for actionable preventive schema and personalized treatment regimes tailored to each individual. It will also entail proactive participation from all major stakeholders in the health care system. We are at the dawn of predictive, preventive, personalized, and participatory （P4） medicine, the fully implementation of which requires marrying basic and clinical researches through advanced systems thinking and the employment of high-throughput technologies in genomics, pro- teomics, nanofluidics, single-cell analysis, and computation strategies in a highly-orchestrated discipline we termed translational systems medicine.