Upstream signalling of mTORC1 and its hyperactivation in type 2 diabetes (T2D)

( Muhammad Ali ),( Shazia Anwer Bukhari ),( Muhammad Ali ),( Han-woong Lee ) 생화학분자생물학회(구 한국생화학분자생물학회) 2017 BMB Reports Vol.50 No.12

Mammalian target of rapamycin complex 1 (mTORC1) plays a major role in cell growth, proliferation, polarity, differentiation, development, and controls transitioning between anabolic and catabolic states of the cell. It collects almost all extracellular and intracellular signals from growth factors, nutrients, and maintains cellular homeostasis, and is involved in several pathological conditions including, neurodegeneration, Type 2 diabetes (T2D), obesity, and cancer. In this review, we summarize current knowledge of upstream signaling of mTORC1 to explain etiology of T2D and hypertriglyceridemia, in which state, the role of telomere attrition is explained. We discuss if chronic inhibition of mTORC1 can reverse adverse effects resulting from hyperactivation. In conclusion, we suggest the regulatory roles of telomerase (TERT) and hexokinase II (HKII) on mTORC1 as possible remedies to treat hyperactivation. The former inhibits mTORC1 under nutrient-rich while the latter under starved condition. We provide an idea of TOS (TOR signaling) motifs that can be used for regulation of mTORC1. [BMB Reports 2017; 50(12): 601-609]

Erratum to: Upstream signalling of mTORC1 and its hyperactivation in type 2 diabetes (T2D)

( Muhammad Ali ),( Shazia Anwer Bukhari ),( Muhammad Ali ),( Han-woong Lee ) 생화학분자생물학회(구 한국생화학분자생물학회) 2018 BMB Reports Vol.51 No.1

Mammalian target of rapamycin complex 1 (mTORC1) plays a major role in cell growth, proliferation, polarity, differentiation, development, and controls transitioning between anabolic and catabolic states of the cell. It collects almost all extracellular and intracellular signals from growth factors, nutrients, and maintains cellular homeostasis, and is involved in several pathological conditions including, neurodegeneration, Type 2 diabetes (T2D), obesity, and cancer. In this review, we summarize current knowledge of upstream signaling of mTORC1 to explain etiology of T2D and hypertriglyceridemia, in which state, the role of telomere attrition is explained. We discuss if chronic inhibition of mTORC1 can reverse adverse effects resulting from hyperactivation. In conclusion, we suggest the regulatory roles of telomerase (TERT) and hexokinase II (HKII) on mTORC1 as possible remedies to treat hyperactivation. The former inhibits mTORC1 under nutrientrich while the latter under starved condition. We provide an idea of TOS (TOR signaling) motifs that can be used for regulation of mTORC1.

Enhanced anti-inflammatory activity of curcumin, a naturally occurring pigment in turmeric via cyclodextrin complexation

Kohli, K,Ali, J,Najmi, AK,Anwer, MT,Ansari, MJ Kyung Hee Oriental Medicine Research Center 2007 Oriental pharmacy and experimental medicine Vol.7 No.2

Curcumin, a dietary pigment responsible for the yellow color of curry, has been used for the treatment of inflammatory diseases and exhibits a variety of pharmacological effects such as anti- inflammatory, anti-tumor, anti-oxidant, and anti-viral activity. In order to examine the potency of the curcumin in inflammation we used carrageenan induced rat hind paw odema model. As curcumin is practically water insoluble, it is hypothesized that pharmacological activity of curcumin could be improved by enhancing its water solubility. Water soluble complexes of curcumin with cyclodextrins were prepared and screened for greater solubility. Pure curcumin 100 mg/kg body weight along with curcumin complexes equivalent to 100 mg/kg body weight of pure curcumin were tested for the anti-inflammatory activity in Wister rats male rats using carrageenan induced hind paw edema model and compared with that of the reference compound diclofenac sodium at a dose level of 10 mg/kg body weight. Results were statistically analyzed using ANOVA. All the treatment groups showed statistically significant anti-inflammatory activity compared with that of vehicle control and positive control.

A novel mutation in RDH5 gene causes retinitis pigmentosa in consanguineous Pakistani family

Neelam Sultan,Irfan Ali,Shazia Anwer Bukhari,Shahid Mahmood Baig,Muhammad Asif,Muhammad Qasim,Muhammad Imran Naseer,Mahmood Rasool 한국유전학회 2018 Genes & Genomics Vol.40 No.5

Retinitis pigmentosa (RP) is the most frequent genetically and clinically heterogeneous inherited retinal degeneration. To date, more than 80 genes have been identified that cause autosomal dominant, autosomal recessive and X linked RP. However, locus and allelic heterogeneity of RP has not been fully captured yet. This heterogeneity and lack of an accurate genotype phenotype correlation makes molecular dissection of the disease more difficult. The present study was designed to characterize the underlying pathogenic variants of RP in Pakistan. For this purpose, a large consanguineous family with RP phenotype showing autosomal recessive mode of inheritance was selected after a complete ophthalmological examination. Next generation sequencing was used for the identification of molecular determinant followed by Sanger-sequencing for confirmation. After sequence analysis a novel homozygous missense mutation, (c.602 C > T) in exon 4 of the RDH5 gene (MIM: 601617) was identified. This mutation resulted in substitution of phenyl alanine for serine at amino acid 201 (p.Ser201Phe) of the RDH5 gene. The same mutation was not detected in the 200 ethnically-matched control samples by Sanger sequencing. The identified mutant allele segregated in homozygous fashion in all the affected individuals of pedigree. Identification of this mutation reveals the allelic heterogeneity of RDH5 in patients with RP phenotype. The findings of this study demonstrate the clinical significance of next generation sequencing to understand the molecular basis of diseases and would help to reveal new proteins and their function in visual cycle will pave the way for early diagnosis, genetic counseling and better therapeutic inventions.

Sustainable Tourism Development: Harvesting the Tourism Potential in Developing Economies through Cluster Development

Muhammad Abdullah,M,Zuhair Murad Khan,M,Ali Anwer 한국문화관광학회 2019 문화관광연구 Vol.21 No.1

It is imperative to view development of tourism sector from a spatial lens. The spatial distribution of the tourism assets of Punjab is dispersed around three distinct zones. Therefore, the Hub and Spoke model, which advocates the development of zones is adopted and three tourism zones are proposed including North Tourism Zone, Lahore Tourism Zone and Southern Tourism Zone. These zones have much to offer in terms of natural beauty, unique landscapes, ethnicity, languages, history, religious attractions, culture and exotic foods. These zones have the potential to accommodate substantial load of local tourism and international tourists

Enhanced anti-inflammatory activity of curcumin, a naturally occurring pigment inturmeric via cyclodextrin complexation

MJ Ansari,K Kohli,J Ali,AK Najmi,MT Anwer 경희대학교 융합한의과학연구소 2007 Oriental Pharmacy and Experimental Medicine Vol.7 No.2

Curcumin, a dietary pigment responsible for the yellow color of curry, has been used for the treatment of inflammatory diseases and exhibits a variety of pharmacological effects such as antiinflammatory, anti-tumor, anti-oxidant, and anti-viral activity. In order to examine the potency of the curcumin in inflammation we used carrageenan induced rat hind paw odema model. As curcumin is practically water insoluble, it is hypothesized that pharmacological activity of curcumin could be improved by enhancing its water solubility. Water soluble complexes of curcumin with cyclodextrins were prepared and screened for greater solubility. Pure curcumin 100 mg/kg body weight along with curcumin complexes equivalent to 100 mg/kg body weight of pure curcumin were tested for the anti-inflammatory activity in Wister rats male rats using carrageenan induced hind paw edema model and compared with that of the reference compound diclofenac sodium at a dose level of 10 mg/kg body weight. Results were statistically analyzed using ANOVA. All the treatment groups showed statistically significant anti-inflammatory activity compared with that of vehicle control and positive control.