Regulation and therapeutic strategies of 4-hydroxy-2-nonenal metabolism in heart disease.

4-Hydroxy-2-nonenal (4-HNE), a reactive aldehyde, is generated from polyunsaturated fatty acids (PUFAs) in biological membranes. Reactive oxygen species (ROS) generated during oxidative stress react with PUFAs to form aldehydes like 4-HNE, which inactivates proteins and DNA by forming hybrid covalent chemical addition compounds called adducts. The ensuing chain reaction results in cellular dysfunction and tissue damage. It includes a wide spectrum of events ranging from electron transport chain dysfunction to apoptosis. In addition, 4-HNE directly depresses contractile function, enhances ROS formation, modulates cell signaling pathways, and can contribute to many cardiovascular diseases, including atherosclerosis, myocardial ischemia-reperfusion injury, heart failure, and cardiomyopathy. Therefore, targeting 4-HNE could help reverse these pathologies. This review will focus on 4-HNE generation, the role of 4-HNE in cardiovascular diseases, cellular targets (especially mitochondria), processes and mechanisms for 4-HNE-induced toxicity, regulation of 4-HNE metabolism, and finally strategies for developing potential therapies for cardiovascular disease by attenuating 4-HNEinduced toxicity.

An Immunity (QL3) Breaking Strain of Sorghum Mosaic Potyvirus in India.

Sorghum (Sorghum bicolor) line Tx2786 is immune to strains or isolates of sorghum mosaic potyvirus (SrMV strains SCH and SCH) but susceptible to strains of maize dwarf mosaic (MDMV) and sugarcane mosaic (SCMV) potyviruses (1,2). When grown in proximity to sugarcane, Tx2786 was infected with a virus that caused mosaic and necrotic symptoms during the postrainy season of 1994 (14 to 30°C) at Parbhani (Maharashtra, India). Leaf-dip electron microscopy performed on virus-infected sorghum and sugarcane tissues revealed particles, 720 × 12 nm, typical of a potyvirus. A potyvirus isolate (designated IBS) was readily transmitted mechanically from field-infected sorghum (Tx2786) and sugarcane (Saccharum officinarum cv. Co.740) to 18 glasshouse-grown sorghum inbred lines. All sorghum lines (QL-3 from India and Tx2786), including those resistant to SrMV, SCMV, MDMV, and johnsongrass mosaic potyvirus (JGMV), were infected. IBS caused necrosis in Cargill-40, Hegari, PI-35038, RTx09, Tx2786, QL-3 from India, and Redlan lines and mosaic symptoms in RTx430, SA-394, Atlas, Martin, BTx3048, Caprock, NM-31, QL-11, SCO-175-14E, Rio, and BTx623 lines. Sorghum reactions to sorghum and sugarcane virus isolates were similar. IBS also infected maize (Zea mays cv. African Tall), johnsongrass (S. halepense cv. 81, symptomless infection), and sorghum (S. bicolor cv. CS-3541) but not prosomillet (Panicum miliaceum), fingermillet (Eleusine coracana cv. IE-2540), pearl millet (Pennisetum typhoides cv. NHB-3), or oat (Avena sativa cv. Kent) when sap transmitted. IBS also was transmitted by the corn leaf aphid (Rhopalosiphum maidis) in a nonpersistent manner from sorghum and sugarcane to all 18 sorghum lines in a glasshouse. Based on direct antigen-coating enzyme-linked immunosorbent assay (DAC-ELISA), serologically specific electron microscopy, and Western blot tests, IBS was serologically related to SrMV strains SCH and SCI (2-4) but not to MDMV strains A, D, and E; SCMV strains A, B, D, SC, and MDB; or JGMV type strain from Australia and strain O from Texas (2). IBS induced formation of cytoplasmic cylindrical inclusions consisting of pinwheels associated with long, straight, laminated aggregates (subdivision type II) in sorghum and sugarcane host cells. Purified IBS contained one major polypeptide of 40 kDa and a ribonucleic acid of 3.0 × 106 Da. Polyclonal antiserum to IBS was produced in rabbits and used in DAC-ELISA to confirm the identity of IBS in sugarcane, sorghum lines, and other test plant species. On the basis of biological and serological properties, IBS isolated from field-infected sorghum grain Tx2786 and sugarcane cv. Co.740 is identified as an immunity (QL3) breaking strain of SrMV (SrMV-IBS). References: (1) L. M. Giorda et al. Plant Dis. 70:624, 1986. (2) D. D. Shukla et al. Phytopathology 79: 223, 1989. (3) D. D. Shukla et al. 1998. AAB Description of Plant Viruses No. 359. AAB, Kew, Surrey, England. (4) Z. N. Yang and T. E. Mirkov. Phytopathology 87:932, 1997.