Madhava Reddy - Academia.edu (original) (raw)

Papers by Madhava Reddy

Research paper thumbnail of Molecular docking and simulation of Curcumin with Geranylgeranyl Transferase1 (GGTase1) and Farnesyl Transferase (FTase)

Research paper thumbnail of Stat3 Signaling Promotes Survival And Maintenance Of Medullary Thymic Epithelial Cells

Research paper thumbnail of γδ T Cell-Mediated Immune Responses in Disease and Therapy

Frontiers in Immunology, 2014

Research paper thumbnail of A Homology Based Model and Virtual Screening of Inhibitors for Human Geranylgeranyl Transferase 1 (GGTase1)

Research paper thumbnail of Stat3 activation plays a role in mTEC development

The Journal of Immunology, Apr 1, 2011

Research paper thumbnail of Human XPC-hHR23B interacts with XPA-RPA in the recognition of triplex-directed psoralen DNA interstrand crosslinks

Nucleic Acids Research, 2005

Research paper thumbnail of Interplay between Human High Mobility Group Protein 1 and Replication Protein A on Psoralen-Cross-linked DNA

Biochemistry, 2005

Human high mobility group box (HMGB) 1 and -2 proteins are highly conserved and abundant chromoso... more Human high mobility group box (HMGB) 1 and -2 proteins are highly conserved and abundant chromosomal proteins that regulate chromatin structure and DNA metabolism. HMGB proteins bind preferentially to DNA that is bent or underwound and to DNA damaged by agents such as cisplatin, UVC radiation, and benzo[a]pyrenediol epoxide (BPDE). Binding of HMGB1 to DNA adducts is thought to inhibit nucleotide excision repair (NER), leading to cell death, but the biological roles of these proteins remain obscure. We have used psoralen-modified triplex-forming oligonucleotides (TFOs) to direct a psoralen-DNA interstrand cross-link (ICL) to a specific site to determine the effect of HMGB proteins on recognition of these lesions. Our results reveal that human HMGB1 (but not HMGB2) binds with high affinity and specificity to psoralen ICLs, and interacts with the essential NER protein, replication protein A (RPA), at these lesions. RPA, shown previously to bind tightly to these lesions, also binds in the presence of HMGB1, without displacing HMGB1. A discrete ternary complex is formed, containing HMGB1, RPA, and psoralen-damaged DNA. Thus, HMGB1 has the ability to recognize ICLs, can cooperate with RPA in doing so, and likely modulates their repair by the NER machinery. The abundance of HMGB1 suggests that it may play an important role in determining the sensitivity of cells to DNA damage under physiological, experimental, and therapeutic conditions.

Research paper thumbnail of Repair of Genome Destabilizing Lesions

Radiation Research, 2005

Living organisms are constantly exposed to detrimental agents both from the environment (e.g. ion... more Living organisms are constantly exposed to detrimental agents both from the environment (e.g. ionizing radiation, ultraviolet light, natural and synthetic chemicals) and from endogenous metabolic processes (e.g. oxidative and hydrolytic reactions), resulting in modifications of proteins, lipids and DNA. Proteins and lipids are degraded and resynthesized, but the DNA is replicated only during cell division, when DNA damage may result in mutation fixation. Thus the DNA damage generated has the potential to lead to carcinogenesis, cell death, or other genetic disorders in the absence of efficient error-free repair. Because modifications in DNA sequence or structure may be incompatible with its essential role in preservation and transmission of genetic information from generation to generation, exquisitely sensitive DNA repair pathways have evolved to maintain genomic stability and cell viability. This review focuses on the repair and processing of genome destabilizing lesions and helical distortions that differ significantly from the canonical B-form DNA in mammalian cells. In particular, we discuss the introduction and processing of site-specific lesions in mammalian cells with an emphasis on psoralen interstrand crosslinks.

Research paper thumbnail of Human HMGB1 directly facilitates interactions between nucleotide excision repair proteins on triplex-directed psoralen interstrand crosslinks

Research paper thumbnail of Effect of 15-lipoxygenase metabolites, 15-( S)-HPETE and 15-( S)-HETE on chronic myelogenous leukemia cell line K-562: Reactive oxygen species (ROS) mediate caspase-dependent apoptosis

Biochemical Pharmacology, 2007

Growth inhibitory effects of 15-lipoxygenase-1 [13-(S)-HPODE and 13-(S)-HODE] and 15-lipoxygenase... more Growth inhibitory effects of 15-lipoxygenase-1 [13-(S)-HPODE and 13-(S)-HODE] and 15-lipoxygenase-2 [15-(S)-HPETE and 15-(S)-HETE] (15-LOX-1 and LOX-2) metabolites and the underlying mechanisms were studied on chronic myeloid leukemia cell line (K-562). The hydroperoxy metabolites, 15-(S)-HPETE and 13-(S)-HPODE rapidly inhibited the growth of K-562 cells by 3h with IC(50) values, 10 and 15microM, respectively. In contrast, the hydroxy metabolite of 15-LOX-2, 15-(S)-HETE, showed 50% inhibition only at 40microM by 6h and 13-(S)-HODE, hydroxy metabolite of 15-LOX-1, showed no significant effect up to 160microM. The cells exposed to 10microM of 15-(S)-HPETE and 40microM of 15-(S)-HETE showed typical apoptotic features like release of cytochrome c, caspase-3 activation and PARP-1 (poly(ADP) ribose polymerase-1) cleavage. A flow cytometry based DCFH-DA analysis and inhibitory studies with DPI, a pharmacological inhibitor of NADPH oxidase, NAC (N-acetyl cysteine) and GSH revealed that NADPH oxidase-mediated generation of ROS is responsible for caspase-3 activation and subsequent induction of apoptosis in the K-562 cell line.

Research paper thumbnail of Bacterial lipopolysaccharide-induced oxidative stress in the impairment of steroidogenesis and spermatogenesis in rats

Reproductive Toxicology, 2006

Research paper thumbnail of C-Phycocyanin, a selective cyclooxygenase-2 inhibitor, induces apoptosis in lipopolysaccharide-stimulated RAW 264.7 macrophages

Biochemical and Biophysical Research Communications, 2003

Research paper thumbnail of Selective Inhibition of Cyclooxygenase2 by C-Phycocyanin, a Biliprotein from Spirulina platensis

Biochemical and Biophysical Research Communications, 2000

Research paper thumbnail of Molecular mechanisms in C-Phycocyanin induced apoptosis in human chronic myeloid leukemia cell line-K562

Biochemical Pharmacology, 2004

Research paper thumbnail of Molecular docking and simulation of Curcumin with Geranylgeranyl Transferase1 (GGTase1) and Farnesyl Transferase (FTase)

Research paper thumbnail of Stat3 Signaling Promotes Survival And Maintenance Of Medullary Thymic Epithelial Cells

Research paper thumbnail of γδ T Cell-Mediated Immune Responses in Disease and Therapy

Frontiers in Immunology, 2014

Research paper thumbnail of A Homology Based Model and Virtual Screening of Inhibitors for Human Geranylgeranyl Transferase 1 (GGTase1)

Research paper thumbnail of Stat3 activation plays a role in mTEC development

The Journal of Immunology, Apr 1, 2011

Research paper thumbnail of Human XPC-hHR23B interacts with XPA-RPA in the recognition of triplex-directed psoralen DNA interstrand crosslinks

Nucleic Acids Research, 2005

Research paper thumbnail of Interplay between Human High Mobility Group Protein 1 and Replication Protein A on Psoralen-Cross-linked DNA

Biochemistry, 2005

Human high mobility group box (HMGB) 1 and -2 proteins are highly conserved and abundant chromoso... more Human high mobility group box (HMGB) 1 and -2 proteins are highly conserved and abundant chromosomal proteins that regulate chromatin structure and DNA metabolism. HMGB proteins bind preferentially to DNA that is bent or underwound and to DNA damaged by agents such as cisplatin, UVC radiation, and benzo[a]pyrenediol epoxide (BPDE). Binding of HMGB1 to DNA adducts is thought to inhibit nucleotide excision repair (NER), leading to cell death, but the biological roles of these proteins remain obscure. We have used psoralen-modified triplex-forming oligonucleotides (TFOs) to direct a psoralen-DNA interstrand cross-link (ICL) to a specific site to determine the effect of HMGB proteins on recognition of these lesions. Our results reveal that human HMGB1 (but not HMGB2) binds with high affinity and specificity to psoralen ICLs, and interacts with the essential NER protein, replication protein A (RPA), at these lesions. RPA, shown previously to bind tightly to these lesions, also binds in the presence of HMGB1, without displacing HMGB1. A discrete ternary complex is formed, containing HMGB1, RPA, and psoralen-damaged DNA. Thus, HMGB1 has the ability to recognize ICLs, can cooperate with RPA in doing so, and likely modulates their repair by the NER machinery. The abundance of HMGB1 suggests that it may play an important role in determining the sensitivity of cells to DNA damage under physiological, experimental, and therapeutic conditions.

Research paper thumbnail of Repair of Genome Destabilizing Lesions

Radiation Research, 2005

Living organisms are constantly exposed to detrimental agents both from the environment (e.g. ion... more Living organisms are constantly exposed to detrimental agents both from the environment (e.g. ionizing radiation, ultraviolet light, natural and synthetic chemicals) and from endogenous metabolic processes (e.g. oxidative and hydrolytic reactions), resulting in modifications of proteins, lipids and DNA. Proteins and lipids are degraded and resynthesized, but the DNA is replicated only during cell division, when DNA damage may result in mutation fixation. Thus the DNA damage generated has the potential to lead to carcinogenesis, cell death, or other genetic disorders in the absence of efficient error-free repair. Because modifications in DNA sequence or structure may be incompatible with its essential role in preservation and transmission of genetic information from generation to generation, exquisitely sensitive DNA repair pathways have evolved to maintain genomic stability and cell viability. This review focuses on the repair and processing of genome destabilizing lesions and helical distortions that differ significantly from the canonical B-form DNA in mammalian cells. In particular, we discuss the introduction and processing of site-specific lesions in mammalian cells with an emphasis on psoralen interstrand crosslinks.

Research paper thumbnail of Human HMGB1 directly facilitates interactions between nucleotide excision repair proteins on triplex-directed psoralen interstrand crosslinks

Research paper thumbnail of Effect of 15-lipoxygenase metabolites, 15-( S)-HPETE and 15-( S)-HETE on chronic myelogenous leukemia cell line K-562: Reactive oxygen species (ROS) mediate caspase-dependent apoptosis

Biochemical Pharmacology, 2007

Growth inhibitory effects of 15-lipoxygenase-1 [13-(S)-HPODE and 13-(S)-HODE] and 15-lipoxygenase... more Growth inhibitory effects of 15-lipoxygenase-1 [13-(S)-HPODE and 13-(S)-HODE] and 15-lipoxygenase-2 [15-(S)-HPETE and 15-(S)-HETE] (15-LOX-1 and LOX-2) metabolites and the underlying mechanisms were studied on chronic myeloid leukemia cell line (K-562). The hydroperoxy metabolites, 15-(S)-HPETE and 13-(S)-HPODE rapidly inhibited the growth of K-562 cells by 3h with IC(50) values, 10 and 15microM, respectively. In contrast, the hydroxy metabolite of 15-LOX-2, 15-(S)-HETE, showed 50% inhibition only at 40microM by 6h and 13-(S)-HODE, hydroxy metabolite of 15-LOX-1, showed no significant effect up to 160microM. The cells exposed to 10microM of 15-(S)-HPETE and 40microM of 15-(S)-HETE showed typical apoptotic features like release of cytochrome c, caspase-3 activation and PARP-1 (poly(ADP) ribose polymerase-1) cleavage. A flow cytometry based DCFH-DA analysis and inhibitory studies with DPI, a pharmacological inhibitor of NADPH oxidase, NAC (N-acetyl cysteine) and GSH revealed that NADPH oxidase-mediated generation of ROS is responsible for caspase-3 activation and subsequent induction of apoptosis in the K-562 cell line.

Research paper thumbnail of Bacterial lipopolysaccharide-induced oxidative stress in the impairment of steroidogenesis and spermatogenesis in rats

Reproductive Toxicology, 2006

Research paper thumbnail of C-Phycocyanin, a selective cyclooxygenase-2 inhibitor, induces apoptosis in lipopolysaccharide-stimulated RAW 264.7 macrophages

Biochemical and Biophysical Research Communications, 2003

Research paper thumbnail of Selective Inhibition of Cyclooxygenase2 by C-Phycocyanin, a Biliprotein from Spirulina platensis

Biochemical and Biophysical Research Communications, 2000

Research paper thumbnail of Molecular mechanisms in C-Phycocyanin induced apoptosis in human chronic myeloid leukemia cell line-K562

Biochemical Pharmacology, 2004