Activities of Venom Proteins and Peptides with Possible Therapeutic Applications from Bees and WASPS.

The variety of proteins and peptides isolated from honey bee venom and wasp venom includes melittin, adiapin, apamine, bradykinin, cardiopep, mast cell degranulating peptide, mastoparan, phospholipase A2 and secapin. Some of the activities they demonstrate may find therapeutic applications.

Ribosome-inactivating Proteins from Root Tubers and Seeds of Trichosan-thes kirilowii and Other Trichosanthes Species.

Ribosome-inactivating proteins have been isolated from Trichosanthes kirilowii root tubers and seeds, including trichosanthin, karasurin and T 33 from root tubers and trichosanthrip, trichokirin, alpha-kirilowin, beta-kirilowin and trichoanguin from seeds. The aforementioned proteins show structural and functional similarities. Among them trichosanthin is the best known and most intensely studied. Trichosanthin manifests anticancer activity in vitro and in tumor bearing mice against a variety of cancers/cancer cell lines. It also exhibits anti-HIV-1 and anti-HSV-1 activities. Trichosanthin has been found to be useful for treatment of cesarean scar pregnancies and ectopic pregnancy, and for preventing acute rejection of major histocompatibility complex-mismatched mouse skin allograft. Trichosanthin selectively lesions some neurons and thus can be used in neuroscience research.

Exaggerated production of nitric oxide (NO) and increases in inducible NO-synthase mRNA levels induced by the pro-inflammatory cytokine interleukin-1beta in vascular smooth muscle cells of elderly rats.

Nitric oxide (NO) is produced at high levels by inducible nitric oxide synthase (iNOS) during inflammation and other pathological conditions, contributing to development of cardiovascular diseases. The present study determined if aging affects the ability of interleukin-1beta (IL-1beta), a pro-inflammatory cytokine, to induce increased NO production (assessed by Griess reaction) and iNOS mRNA levels (assessed by RT-PCR/agarose gel electrophoresis) in vascular smooth muscle cells (VSMCs) from young (3-month-old) and elderly (20-22-month-old) rats. The VSMCs cells were used only in early passages (passages 0 and 1) to avoid phenotypic modulation. To uncover subtle differences in basal iNOS mRNA levels in VSMCs of young and elderly rats, RT-PCR products were also analyzed by a new ultrasensitive technique using capillary electrophoresis with laser-induced fluorescence detector (CE-LIF). IL-1beta (5 ng/ml) significantly (P < 0.05) increased NO production 3.7-fold in elderly female VSMCs and 6.7-fold in elderly male VSMCs, but had no detectable effect in young female and male VSMCs. Basal iNOS mRNA levels (assessed by RT-PCR/CE-LIF) were dramatically higher in VSMCs of elderly male rats compared to young ones. In general, VSMCs of elderly rats showed much greater sensitively to iNOS-inducing actions of IL-1beta. These data give new insight into effects of aging on iNOS expression in VSMCs, showing dramatic increases in both basal and stimulated iNOS mRNA levels, which may contribute to the development of vascular diseases in the elderly.

Severe impairment of CGRP-induced hypotension in vivo and vasorelaxation in vitro in elderly rats.

The aim of this study was to investigate the effects of aging on hypotension in vivo and vasorelaxation in vitro induced by calcitonin gene-related peptide (CGRP), using young (3 months old) and elderly (20 and 28 months old) Sprague-Dawley rats. Vasorelaxant responses were measured in isolated rings of rat thoracic aorta and rat caudal artery, which show endothelium-dependent and endothelium-independent responses to CGRP, respectively. The CGRP-induced vasorelaxations were significantly diminished in 28-month-old male rats in both aorta (39.3% of responses in young controls at 10 nM CGRP) and caudal artery (28.5% of responses in young controls at 10 nM CGRP). Acetylcholine caused vasorelaxations in aortic rings of young male rats, but vasocontractions in aortic rings of 28-month-old male rats. Hypotension induced by CGRP was significantly diminished in both 20-month-old male rats (47.7% of young controls) and 20-month-old female rats (34.4% of young controls). Moreover, ovariectomy, known to decrease CGRP-induced hypotension in young female rats, did not further decrease hypotension to CGRP in elderly female rats. In conclusion, vasorelaxant responses in vitro and hypotensive responses in vivo induced by the neuropeptide CGRP are severely impaired in elderly rats as compared to young rats. The data suggest that the vasodilatory responses to CGRP in both large arteries and the small resistance-sized arteries regulating arterial blood pressure are damaged or down-regulated by the aging process.