Review
Cell Biology
Cecilia Astigiano, Andrea Benzi, Maria Elena Laugieri, Francesco Piacente, Laura Sturla, Lucrezia Guida, Santina Bruzzone, Antonio De Flora
Summary: ADP-ribosyl cyclases (ADPRCs) catalyze the synthesis of the Ca2+-active second messengers Cyclic ADP-ribose (cADPR) and ADP-ribose (ADPR) from NAD(+) as well as nicotinic acid adenine dinucleotide phosphate (NAADP(+)) from NADP(+). CD38 is the best characterized ADPRC in mammals, with two opposite membrane orientations: type II and type III. Type II CD38 is a glycosylated ectoenzyme, while type III CD38 has its active site in the cytosol.
Article
Cell Biology
Long Gao, Yuan Liu, Xiaohong Du, Sai Ma, Minmin Ge, Haijun Tang, Chenfeng Han, Xin Zhao, Yanbin Liu, Yun Shao, Zhao Wu, Lianjun Zhang, Fang Meng, F. Xiao-Feng Qin
Summary: The upregulation of tumor-associated CD38 in lung adenocarcinoma is correlated with poor survival of patients, and facilitates cancer cell migration, proliferation, colony formation, and tumor development. Inhibition of CD38's enzymatic activity may represent an important strategy for preventing tumor progression.
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Bo Shi, Wenxia Wang, Benjamin Korman, Li Kai, Qianqian Wang, Jun Wei, Swarna Bale, Roberta Goncalves Marangoni, Swati Bhattacharyya, Stephen Miller, Dan Xu, Mahzad Akbarpour, Paul Cheresh, Daniele Proccissi, Demirkan Gursel, Jair Machado Espindola-Netto, Claudia C. S. Chini, Guilherme C. de Oliveira, Johann E. Gudjonsson, Eduardo N. Chini, John Varga
Summary: The upregulation of CD38 in patients with systemic sclerosis leads to disrupted NAD(+) homeostasis, driving fibrosis. CD38 enhances cellular fibrotic responses by reducing NAD(+) levels and sirtuin activity. Inhibiting CD38 may be a new therapeutic approach for fibrosis in systemic sclerosis.
Article
Multidisciplinary Sciences
Kasper Fugger, Ilirjana Bajrami, Mariana Silva Dos Santos, Sarah Jane Young, Simone Kunzelmann, Geoff Kelly, Graeme Hewitt, Harshil Patel, Robert Goldstone, Thomas Carell, Simon J. Boulton, James MacRae, Ian A. Taylor, Stephen C. West
Summary: Mutations in BRCA1 or BRCA2 genes increase the risk of breast and ovarian cancer, but inhibiting DNPH1 can enhance the sensitivity of BRCA-deficient cells to PARP inhibitors. Targeting DNPH1 provides a promising strategy for hypersensitizing BRCA-deficient cancers to PARPi therapy.
Article
Multidisciplinary Sciences
Hassan Morad, Suaib Luqman, Chun-Hsiang Tan, Victoria Swann, Peter A. McNaughton
Summary: The study demonstrates that neutrophils accurately navigate towards pathogens by activating TRPM2 ion channels to generate intracellular leading-edge calcium pulses. This mechanism is not only observed for hydrogen peroxide but also for other chemoattractants. Leading-edge calcium pulses are proposed as the universal drivers of the motile machinery involved in neutrophil chemotaxis.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Multidisciplinary
Thomas Z. Benton, Catherine M. Mills, Jonathan M. Turner, Megan J. Francis, Dalan J. Solomon, Pieter B. Burger, Yuri K. Peterson, Nathan G. Dolloff, Andre S. Bachmann, Patrick M. Woster
Summary: CD38 ectoenzyme is expressed on the surface of mature immune cells and tumor cells such as multiple myeloma, acting as a marker for cell activation. Small molecule inhibitors selective for CD38 hydrolase or cyclase activity have been identified and shown to activate T cells, potentially serving as novel immunotherapeutic agents.
Article
Neurosciences
Han-Wei Liu, Li-Na Gong, Ke Lai, Xia-Fei Yu, Zhen-Qi Liu, Ming-Xian Li, Xin-Lu Yin, Min Liang, Hao-Song Shi, Lin-Hua Jiang, Wei Yang, Hai-Bo Shi, Lu-Yang Wang, Shan-Kai Yin
Summary: Stroke prognosis is negatively affected by elevated levels of serum bilirubin, but the mechanism of how bilirubin worsens outcomes is still unknown. This study found that post-stroke bilirubin levels, but not pre-stroke levels, are associated with infarct volume in hospitalized patients. Mouse models showed that bilirubin increases neuronal excitability and ischemic infarct size, and ischemic insults trigger the release of endogenous bilirubin, which activates TRPM2 channels. Knockout or antagonization of the TRPM2 channel attenuates these effects. These findings suggest a vicious cycle of stroke injury involving the release of endogenous bilirubin and activation of TRPM2 channels, exacerbating Ca2+-dependent brain injury.
Article
Biochemistry & Molecular Biology
David Hutin, Karoline Alvik Hagen, Peng Shao, Kim Sugamori, Denis M. Grant, Jason Matthews
Summary: PARP7 is an important regulator of the immune system, and is involved in intestinal inflammation. Loss of PARP7 impairs immune response to colon inflammation, possibly due to its role in IFN-I signaling rather than AHR signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biology
Andras Szollosi
Summary: The TRPM family, particularly TRPM2, plays essential roles in cellular functions such as body heat control, immune cell activation, and insulin secretion. Recent studies have advanced our understanding of the biophysical properties of TRPM2 and revealed mechanistic differences among channel orthologues. Further research is needed to fully understand the structure-function relationships of TRPM2.
Article
Biology
Wan Hua Li, Ke Huang, Yang Cai, Qian Wen Wang, Wen Jie Zhu, Yun Nan Hou, Sujing Wang, Sheng Cao, Zhi Ying Zhao, Xu Jie Xie, Yang Du, Chi-Sing Lee, Hon Cheung Lee, Hongmin Zhang, Yong Juan Zhao
Summary: By designing and synthesizing specific fluorescent conjugates, the activation process of SARM1 was predicted and visualized, while a derivative of nisoldipine was found to inhibit SARM1 activation, protecting neuronal axons from degeneration.
Article
Multidisciplinary Sciences
Keisuke Yaku, Sailesh Palikhe, Hironori Izumi, Tomoyuki Yoshida, Keisuke Hikosaka, Faisal Hayat, Mariam Karim, Tooba Iqbal, Yasuhito Nitta, Atsushi Sato, Marie E. Migaud, Katsuhiko Ishihara, Hisashi Mori, Takashi Nakagawa
Summary: Nicotinamide riboside increases NAD(+) levels through two pathways, directly generating NAD(+) via the NR salvage pathway and contributing to NAD(+) production through the Preiss-Handler pathway after being hydrolyzed by BST1.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Keum-Young So, Seon-Hee Oh
Summary: Arsenic induces a distinctive cell death mode via PARP-1 activation in p53-deficient cells. This cell death is promoted by autophagy inhibition. These findings suggest that PARP-1 activation could be used as an effective therapeutic approach for arsenic toxicity in p53-deficient cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Cell Biology
Cherng-Shyang Chang, Yi-Chu Liao, Chih-Ting Huang, Chiao-Mei Lin, Chantal Hoi Yin Cheung, Jhen-Wei Ruan, Wen-Hsuan Yu, Yi-Ting Tsai, I-Jung Lin, Chien-Hsun Huang, Jong-Shian Liou, Ya-Hsien Chou, Hung-Jen Chien, Hsiao-Li Chuang, Hsueh-Fen Juan, Hsuan-Cheng Huang, Hong-Lin Chan, Yu-Chieh Liao, Shiue-Cheng Tang, Yu-Wen Su, Tse-Hua Tan, Andreas J. Baeumler, Cheng-Yuan Kao
Summary: The knockout of Dusp6 enhances baseline colon barrier integrity and ameliorates DSS-induced colonic injury, accompanied by altered glucose metabolism and increased mitochondrial oxygen consumption in Caco-2 cells. Dusp6-knockout mice are more resistant to DSS-induced dysbiosis, and a member of the genus Duncaniella in the gut microbiota confers host protection from injury.
Article
Biochemistry & Molecular Biology
Yoshinori Takeda, Asako Itaya-Hironaka, Akiyo Yamauchi, Mai Makino, Sumiyo Sakuramoto-Tsuchida, Hiroyo Ota, Ryuji Kawaguchi, Shin Takasawa
Summary: This study found that sleep apnea syndrome leads to increased mRNA levels of renin and CD38 genes, resulting in hypertension. The upregulation of these genes can be abolished by introducing a miR-203 mimic.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Uh-Hyun Kim
Summary: In this review, the roles of cADPR and NAADP in pancreatic beta cells are summarized, along with the intracellular Ca2+ stores and Ca2+ channels they target. Studying the roles of these signaling messengers helps us understand Ca2+ signaling and pathophysiology.