Isoforms of the smooth muscle myosin phosphatase targeting subunit 1 (MYPT1) are generated by cassette-type alternative splicing of exons. Tissue-specific expression of these isoforms is thought to determine smooth muscle-relaxant properties and unique responses to signaling pathways. We used mini-gene deletion/mutation constructs to identify cis regulators of splicing of the chicken MYPT1 central alternative exon. Comparisons of alternative exon splicing were made between smooth muscle cells of the fast-phasic contractile phenotype (gizzard), in which the central alternative exon is skipped, and slow tonic contractile phenotype (aorta), in which the alternative exon is included. We demonstrate that splicing of the alternative exon requires a cis-enhancer complex in the vicinity of the alternative exon 5'-splice site. This complex consists of two UCUU motifs in an intronic U-rich sequence (putative PTB (polypyrimidine tract binding) or T cell inhibitor of apoptosis-1 binding sites), an intronic 67-nucleotide enhancer that has similarities with the cardiac Troponin T MSE3 enhancer, and a potentially novel exonic splicing enhancer. The exonic enhancer contains the palindromic sequence UCCUACAUCCU present in many other transcripts where alternative splicing of exons occurs, suggesting that it may be more broadly active. The exonic enhancer is adjacent to a potentially novel exonic silencer element that contains a 13-nucleotide imperfect palindromic sequence. This silencer, in conjunction with a distal intronic silencer, is proposed to mediate the silencing of splicing of the MYPT1 central alternative exon in the fast phasic smooth muscle phenotype

Dynamic economical and industrial expansion lead to environmental contamination and pollution with increasing amounts of harmful agents. Recently, dioxins and dioxin-like compounds (DLCs) have received much attention due to their widespread occurrence, high levels of toxicity, and the significant threat these compounds pose to humans. In this study, we investigated renal toxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and explained the role of pumpkin seed oil in modulating TCDD toxicity in the kidney of Wister albino rats. Thirty male and female Wister rats were divided into three isolated groups ten animal each. Group 1 (G1) served as normal control, group 2 (G2), rats were received single intraperitoneal dose of TCDD (2μg/kg b.w. dissolved in corn oil), while group 3 (G3), rats were treated with oral pumpkin seed oil (PO) (1.5 ml/kg b.w. day after day) after TCDD treatment (same as group II). Blood samples were collected for biochemical analysis and kidney tissue samples for histological examination. our investigation revealed that, TCDD induced significant increase (P<0.01) in urea level and significant increase in creatinine level (P<0.05) in comparison to control group. TCDD treated rats showed series of renal histopathological alterations present mostly in renal vasculature associated with severe degeneration and necrosis of renal tubular epithelium. The previous mentioned lesions were reported much more prominent in renal medulla than in renal cortex. Interestingly, PO treated group showed significant increase (P<0.001) in urea level and significant decrease (P<0.05) in comparison with TCDD group. PO treatment ameliorates these biochemical and pathological changes in renal tissue. In conclusion, exposure to 2, 3, 7, 8-TCDD led to serious toxic effects in renal tissue and treatment with PO could diminish this toxicity to an improved extend.

1. Isoforms of the smooth muscle myosin phosphatase targeting subunit 1 (MYPT1) are generated by cassette-type alternative splicing of exons. Tissue-specific expression of these isoforms is thought to determine smooth muscle-relaxant properties and unique responses to signaling pathways. We used mini-gene deletion/mutation constructs to identify cis regulators of splicing of the chicken MYPT1 central alternative exon. Comparisons of alternative exon splicing were made between smooth muscle cells of the fast-phasic contractile phenotype (gizzard), in which the central alternative exon is skipped, and slow tonic contractile phenotype (aorta), in which the alternative exon is included. We demonstrate that splicing of the alternative exon requires a cis-enhancer complex in the vicinity of the alternative exon 5'-splice site. This complex consists of two UCUU motifs in an intronic U-rich sequence (putative PTB (polypyrimidine tract binding) or T cell inhibitor of apoptosis-1 binding sites), an intronic 67-nucleotide enhancer that has similarities with the cardiac Troponin T MSE3 enhancer, and a potentially novel exonic splicing enhancer. The exonic enhancer contains the palindromic sequence UCCUACAUCCU present in many other transcripts where alternative splicing of exons occurs, suggesting that it may be more broadly active. The exonic enhancer is adjacent to a potentially novel exonic silencer element that contains a 13-nucleotide imperfect palindromic sequence. This silencer, in conjunction with a distal intronic silencer, is proposed to mediate the silencing of splicing of the MYPT1 central alternative exon in the fast phasic smooth muscle phenotype.

Dynamic economical and industrial expansion lead to environmental contamination and pollution with increasing amounts of harmful agents. Recently, dioxins and dioxin-like compounds (DLCs) have received much attention due to their widespread occurrence, high levels of toxicity, and the significant threat these compounds pose to humans. In this study, we investigated renal toxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and explained the role of pumpkin seed oil in modulating TCDD toxicity in the kidney of Wister albino rats. Thirty male and female Wister rats were divided into three isolated groups ten animal each. Group 1 (G1) served as normal control, group 2 (G2), rats were received single intraperitoneal dose of TCDD (2μg/kg b.w. dissolved in corn oil), while group 3 (G3), rats were treated with oral pumpkin seed oil (PO) (1.5 ml/kg b.w. day after day) after TCDD treatment (same as group II). Blood samples were collected for biochemical analysis and kidney tissue samples for histological examination. our investigation revealed that, TCDD induced significant increase (P<0.01) in urea level and significant increase in creatinine level (P<0.05) in comparison to control group. TCDD treated rats showed series of renal histopathological alterations present mostly in renal vasculature associated with severe degeneration and necrosis of renal tubular epithelium. The previous mentioned lesions were reported much more prominent in renal medulla than in renal cortex. Interestingly, PO treated group showed significant increase (P<0.001) in urea level and significant decrease (P<0.05) in comparison with TCDD group. PO treatment ameliorates these biochemical and pathological changes in renal tissue. In conclusion, exposure to 2, 3, 7, 8-TCDD led to serious toxic effects in renal tissue and treatment with PO could diminish this toxicity to an improved extend.

The prostate gland considers the most important gland among rabbits' accessory genital glands and secretes many factors essential for sperm function. This study aims to show the impact of Maca as an antioxidant on the prostate gland's histomorphology and its capacity to reduce the effects of oxidative stress. Twenty-four healthy New Zealand white male rabbits, 6-8 months divided into 4 groups.1st group (control group), 2nd group (Maca), 3rd group (H2O2), 4th group (Maca+ H2O2). To evaluate these effects we used histomorphometrical studies. In control and Maca groups, acini were lined by simple columnar epithelium and showed normal interstitium. However, in H2O2 treated rabbits, we observed cuboidal epithelium and epithelium height decreased significantly compared to other groups, and interstitium showed fibrosis. Also in H2O2 treated rabbits, we observed mild degenerative changes in the epithelial lining the acini, with karyolitic nucleus and vacuolated cytoplasm. In concern to acini length, we observed that the secretory units in Maca groups was overcrowd due to increasing acini length. However, in H2O2 exposed rabbits the diameter of the glandular portion and the length of the acini decreased significantly compared to other groups. Moreover in H2O2 treated rabbits we demonstrated other changes as congested and hyperemic blood vessels and muscular layer appeared disorganized and degenerated. In Maca+ H2O2 (H+M) treated rabbits the epithelium reverted to simple columnar and the secretory activity increased compared to H2O2 group. In conclusion, we can ensure the effect of Maca as an anti-oxidant and its ameliorative effect on oxidative stressed rabbits.

The prostate gland considers the most important gland among rabbits' accessory genital glands and secretes many factors essential for sperm function. This study aims to show the impact of Maca as an antioxidant on the prostate gland's histomorphology and its capacity to reduce the effects of oxidative stress. Twenty-four healthy New Zealand white male rabbits, 6-8 months divided into 4 groups.1st group (control group), 2nd group (Maca), 3rd group (H2O2), 4th group (Maca+ H2O2). To evaluate these effects we used histomorphometrical studies. In control and Maca groups, acini were lined by simple columnar epithelium and showed normal interstitium. However, in H2O2 treated rabbits, we observed cuboidal epithelium and epithelium height decreased significantly compared to other groups, and interstitium showed fibrosis. Also in H2O2 treated rabbits, we observed mild degenerative changes in the epithelial lining the acini, with karyolitic nucleus and vacuolated cytoplasm. In concern to acini length, we observed that the secretory units in Maca groups was overcrowd due to increasing acini length. However, in H2O2 exposed rabbits the diameter of the glandular portion and the length of the acini decreased significantly compared to other groups. Moreover in H2O2 treated rabbits we demonstrated other changes as congested and hyperemic blood vessels and muscular layer appeared disorganized and degenerated. In Maca+ H2O2 (H+M) treated rabbits the epithelium reverted to simple columnar and the secretory activity increased compared to H2O2 group. In conclusion, we can ensure the effect of Maca as an anti-oxidant and its ameliorative effect on oxidative stressed rabbits.